Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

NASA Technical Reports Server (NTRS)

Ishihara, A.; Roy, R. R.; Edgerton, V. R.

1995-01-01

The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data provide evidence for an interdependence in the oxidative capacity between a motoneuron and its target muscle fibres in two subpopulations of motoneurons from the same motor pool, i.e. the same muscle.

Development of the peptidergic innervation of human heart.

PubMed Central

Gordon, L; Polak, J M; Moscoso, G J; Smith, A; Kuhn, D M; Wharton, J

1993-01-01

The aim of the present investigation was to study the developing peptidergic innervation of the human fetal heart of 7-24 wk gestational age. An immunohistochemical approach was adopted and the total innervation visualised with antisera to general neuronal and Schwann cell markers, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immunoreactive nerves were not observed until the 10th week of gestation. NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide-containing nerves identified in the fetal heart, exhibiting a descending atrial to ventricular density gradient, and were first identified during the 10th wk of gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of gestation and were mainly distributed in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other peptide-containing nerves appear to be of extrinsic origin, including those immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated before the adrenergic innervation has previously been shown to be present by formaldehyde-induced fluorescence staining of catecholamines. The onset of the CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent innervation occurs later than the autonomic. The differential appearance and distribution of peptide-containing nerve subpopulations indicate that there is a chronological order to the development of the autonomic and sensory components of human cardiac innervation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7505778

Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

PubMed

Scheerer, Claudia; Frangini, Sergio; Chiantera, Vito; Mechsner, Sylvia

2017-09-01

Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

PubMed Central

Corey, Sarah M.; Vizzard, Margaret A.; Badger, Gary J.; Langevin, Helene M.

2011-01-01

Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

Vertebral body innervation: Implications for pain.

PubMed

Buonocore, Michelangelo; Aloisi, Anna Maria; Barbieri, Massimo; Gatti, Anna Maria; Bonezzi, Cesare

2010-03-01

Vertebral fractures often cause intractable pain. To define the involvement of vertebral body innervation in pain, we collected specimens from male and female patients during percutaneous kyphoplasty, a procedure used for reconstruction of the vertebral body. Specimens were taken from 31 patients (9 men and 22 women) suffering high-intensity pain before surgery. In total, 1,876 histological preparations were obtained and analysed. Immunohistochemical techniques were used to locate the nerves in the specimens. The nerve fibres were labelled by indirect immunofluorescence with the primary antibody directed against Protein Gene Product 9.5 (PGP 9.5), a pan-neuronal marker; another primary antibody directed against type IV collagen (Col IV) was used to identify vessels and to determine their relationship with vertebral nerve fibres. The mean percentage of samples in which it was possible to identify nerve fibres was 35% in men and 29% in women. The percentages varied depending on the spinal level considered and the sex of the subject, nerve fibres being mostly present around vessels (95%). In conclusion, there is scarce innervation of the vertebral bodies, with a clear prevalence of fibres located around vessels. It seems unlikely that this pattern of vertebral body innervation is involved in vertebral pain or in pain relief following kyphoplasty.

Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

PubMed

Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

2015-01-01

Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments. The gland size correlates to the size of a neuron soma in the suboesophageal ganglion, which likely controls gland contraction. In P. schultei, the innervation pattern appears simplified to the anterior suboesophageal nerve. Hence, some evolutionary changes are notable in a conserved neuronal network.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

PubMed

Rukhadze, I; Kamani, H; Kubin, L

2011-12-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.

PubMed

Sørensen, Christiane Elisabeth; Larsen, Jytte Overgaard; Reibel, Jesper; Lauritzen, Martin; Mortensen, Erik Lykke; Osler, Merete; Pedersen, Anne Marie Lynge

2014-09-01

One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands. Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology. Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the parenchymal autonomic innervation, whereas inflammatory processes may compromise it by alternative mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion

PubMed Central

Hoang, John; Bruce-Keller, Annadora; Berthoud, Hans-Rudolf; Morrison, Christopher D.

2017-01-01

The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHAGABA), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHAGABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHAGABA neurons that coexpress the neuropeptide galanin (LHAGal). These LHAGal neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHAGal neurons may represent a subpopulation of LHAGABA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHAGal or LHAGABA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHAGal or LHAGABA neuronal activation both increased operant food-seeking behavior, but only activation of LHAGABA neurons increased overall chow consumption. Additionally, LHAGal or LHAGABA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHAGABA neurons induced compulsive-like locomotor behavior; while LHAGal neurons induced locomotor activity without compulsivity. Thus, LHAGal neurons define a subpopulation of LHAGABA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. SIGNIFICANCE STATEMENT The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHAGABA neurons is heterogeneous and largely undefined. Here we introduce LHAGal neurons as a subset of LHAGABA neurons that lack direct innervation of the ventral tegmental area (VTA). LHAGal neurons are sufficient to drive motivated feeding and locomotor activity similar to LHAGABA neurons, but without inducing compulsive-like behaviors, which we propose to require direct VTA innervation. Our study integrates galanin-expressing LHA neurons into our current understanding of the neuronal circuits and molecular mechanisms of the LHA that contribute to motivated feeding behaviors. PMID:28539422

Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb.

PubMed

Gómez, C; Briñón, J G; Barbado, M V; Weruaga, E; Valero, J; Alonso, J R

2005-06-01

The centrifugal systems innervating the olfactory bulb are important elements in the functional regulation of the olfactory pathway. In this study, the selective innervation of specific glomeruli by serotonergic, noradrenergic and cholinergic centrifugal axons was analyzed. Thus, the morphology, distribution and density of positive axons were studied in the glomerular layer of the main olfactory bulb of the rat, using serotonin-, serotonin transporter- and dopamine-beta-hydroxylase-immunohistochemistry and acetylcholinesterase histochemistry in serial sections. Serotonin-, serotonin transporter-immunostaining and acetylcholinesterase-staining revealed a higher heterogeneity in the glomerular layer of the main olfactory bulb than previously reported. In this sense, four types of glomeruli could be identified according to their serotonergic innervation. The main distinctive feature of these four types of glomeruli was their serotonergic fibre density, although they also differed in their size, morphology and relative position throughout the rostro-caudal main olfactory bulb. In this sense, some specific regions of the glomerular layer were occupied by glomeruli with a particular morphology and a characteristic serotonergic innervation pattern that was consistent from animal to animal. Regarding the cholinergic system, we offer a new subclassification of glomeruli based on the distribution of cholinergic fibres in the glomerular structure. Finally, the serotonergic and cholinergic innervation patterns were compared in the glomerular layer. Sexual differences concerning the density of serotonergic fibres were observed in the atypical glomeruli (characterized by their strong cholinergic innervation). The present report provides new data on the heterogeneity of the centrifugal innervation of the glomerular layer that constitutes the morphological substrate supporting the existence of differential modulatory levels among the entire glomerular population.

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

Neurons and terminals in the retrohippocampal region in the rat's brain identified by anti-gamma-aminobutyric acid and anti-glutamic acid decarboxylase immunocytochemistry.

PubMed

Köhler, C; Wu, J Y; Chan-Palay, V

1985-01-01

The distribution of gamma-aminobutyric acid (GABA) containing nerve cells and terminals was studied at the light and electron microscopic levels in the retrohippocampal region of the rat by using anti-glutamic acid decarboxylase (GAD) and anti-GABA antibodies in immunocytochemistry. Large numbers of GAD and GABA stained cells were found in all retrohippocampal structures. At the ultrastructural level, the immunoreactivity against GABA and against the synthesizing enzyme GAD was localized to cytoplasmic structures, including loose clumps of rough endoplasmic reticulum, ribosomal arrays, outer mitochondrial surfaces and in axonal boutons. The GAD- and GABA-immunoreactive(-i) cells were found in all subfields of the retrohippocampal region (e.g., the subicular complex, the entorhinal area). Within the entorhinal area a slightly larger number of immunoreactive cells could be detected in layers II and III than in the other layers. In the subiculum, pre- and parasubiculum the GAD and GABA-i cells were present in relatively large numbers in all layers, except the molecular layer, which contained only a small number of GABA cells. Within the entorhinal area, GAD and GABA stained cells ranged in size from small (13 micron in diameter) to large (22 micron in diameter). A large number of different morphological classes of cells were found, except pyramidal and stellate cells. In the pre- and parasubiculum, on the other hand, the GABA cells were generally small to medium in size and morphologically more homogeneous than in the subiculum and entorhinal area. The entire retrohippocampal region was densely innervated by GABA preterminal processes, with little variation in the regional density of innervation. Within the entorhinal area, presubiculum and subiculum, a clear difference was found in the laminar pattern of innervation. In all three subfields the densest innervation was in layer II. In the entorhinal area both GAD- and GABA-i axons form palisades of fibers around the somata of neurons, which are tightly packed together in this layer. In the electron microscope both GAD-i and GABA-i were demonstrated in these axons. Axosomatic synaptic contacts were common between axons and the stellate neurons and other cells of this layer. Layers IV and VI appeared less dense in GAD-i terminals but appeared more densely innervated than layers III and V. The lamina dessicans was relatively poor in GAD-i. In the subiculum and presubiculum, as well as all other subfields of the hippocampal region, the innervation is dominated by axo-somatic innervation of layer II cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro-esophageal reflux disease?

PubMed

Powley, T L; Gilbert, J M; Baronowsky, E A; Billingsley, C N; Martin, F N; Phillips, R J

2012-10-01

The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Sprague-Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days postinjection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal (ICC) were counterstained. The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with ICC. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings, the two types of mechanoreceptors found throughout stomach smooth muscle. The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors. © 2012 Blackwell Publishing Ltd.

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers

PubMed Central

Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

2018-01-01

Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB− fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. PMID:28600222

Efferent innervation of turtle semicircular canal cristae: comparisons with bird and mouse

PubMed Central

Jordan, Paivi M.; Fettis, Margaret; Holt, Joseph C.

2014-01-01

In the vestibular periphery of nearly every vertebrate, cholinergic vestibular efferent neurons give rise to numerous presynaptic varicosities that target hair cells and afferent processes in the sensory neuroepithelium. Although pharmacological studies have described the postsynaptic actions of vestibular efferent stimulation in several species, characterization of efferent innervation patterns and the relative distribution of efferent varicosities among hair cells and afferents are also integral to understanding how efferent synapses operate. Vestibular efferent markers, however, have not been well characterized in the turtle, one of the animal models utilized by our laboratory. Here, we sought to identify reliable efferent neuronal markers in the vestibular periphery of turtle, to utilize these markers to understand how efferent synapses are organized, and to compare efferent neuronal labeling patterns in turtle with two other amniotes using some of the same markers. Efferent fibers and varicosities were visualized in the semicircular canal of Red-Eared Turtles (Trachemys scripta elegans), Zebra Finches (Taeniopygia guttata), and mice (Mus musculus) utilizing fluorescent immunohistochemistry with antibodies against choline acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a population of small diameter fibers giving rise to numerous spherical varicosities abutting type II hair cells and afferent processes. That these ChAT-positive varicosities represent presynaptic release sites were demonstrated by colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2, or syntaxin and the neuropeptide calcitonin gene-related peptide (CGRP). Comparisons of efferent innervation patterns among the three species are discussed. PMID:25560461

Efferent innervation of turtle semicircular canal cristae: comparisons with bird and mouse.

PubMed

Jordan, Paivi M; Fettis, Margaret; Holt, Joseph C

2015-06-01

In the vestibular periphery of nearly every vertebrate, cholinergic vestibular efferent neurons give rise to numerous presynaptic varicosities that target hair cells and afferent processes in the sensory neuroepithelium. Although pharmacological studies have described the postsynaptic actions of vestibular efferent stimulation in several species, characterization of efferent innervation patterns and the relative distribution of efferent varicosities among hair cells and afferents are also integral to understanding how efferent synapses operate. Vestibular efferent markers, however, have not been well characterized in the turtle, one of the animal models used by our laboratory. Here we sought to identify reliable efferent neuronal markers in the vestibular periphery of turtle, to use these markers to understand how efferent synapses are organized, and to compare efferent neuronal labeling patterns in turtle with two other amniotes using some of the same markers. Efferent fibers and varicosities were visualized in the semicircular canal of red-eared turtles (Trachemys scripta elegans), zebra finches (Taeniopygia guttata), and mice (Mus musculus) utilizing fluorescent immunohistochemistry with antibodies against choline acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a population of small diameter fibers giving rise to numerous spherical varicosities abutting type II hair cells and afferent processes. That these ChAT-positive varicosities represent presynaptic release sites were demonstrated by colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2, or syntaxin and the neuropeptide calcitonin gene-related peptide. Comparisons of efferent innervation patterns among the three species are discussed. © 2015 Wiley Periodicals, Inc.

Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart.

PubMed

Fregoso, S P; Hoover, D B

2012-09-27

Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous system in the heart. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation.

PubMed

Yanai, Joseph; Huleihel, Rabab; Izrael, Michal; Metsuyanim, Sally; Shahak, Halit; Vatury, Ori; Yaniv, Shiri P

2003-09-01

Opioid drugs act primarily on the opiate receptors; they also exert their effect on other innervations resulting in non-opioidergic behavioural deficits. Similarly, opioid neurobehavioural teratogenicity is attested in numerous behaviours and neural processes which hinder the research on the mechanisms involved. Therefore, in order to be able to ascertain the mechanism we have established an animal (mouse) model for the teratogenicity induced by opioid abuse, which focused on behaviours related to specific brain area and innervation. Diacetylmorphine (heroin) and not morphine was applied because heroin exerts a unique action, distinguished from that of morphine. Pregnant mice were exposed to heroin (10 mg/kg per day) and the offspring were tested for behavioural deficits and biochemical alterations related to the septohippocampal cholinergic innervation. Some studies employing the chick embryo were concomitantly added as a control for the confounding indirect variables. Prenatal exposure to heroin in mice induced global hyperactivation both pre- and post-synaptic along the septohippocampal cholinergic innervation, including basal protein kinase C (PKC) activity accompanied by a desensitization of PKC activity in response to cholinergic agonist. Functionally, the heroin-exposed offspring displayed deficits in hippocampus-related behaviours, suggesting deficits in the net output of the septohippocampal cholinergic innervation. Grafting of cholinergic cells to the impaired hippocampus reversed both pre- and post-synaptic hyperactivity, resensitized PKC activity, and restored the associated behaviours to normality. Consistently, correlation studies point to the relative importance of PKC to the behavioural deficits. The chick model, which dealt with imprinting related to a different brain region, confirmed that the effect of heroin is direct. Taken together with studies by others on the effect of prenatal exposure to opioids on the opioidergic innervation and with what is known on the opioid regulation of the cholinergic innervation, it appears that heroin exerts its neuroteratogenicity by inducing alterations in the opioidergic innervation, which by means of its regulatory action, attenuates the functional output of the cholinergic innervation. In our model, there was hyperactivity mostly of the post-synaptic components of the cholinergic innervation. However, the net cholinergic output is decreased because PKC is desensitized to the effect of the cholinergic agonist, and this is further evidenced by the extensive deficits in the related behaviours.

Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

PubMed

van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

2016-05-01

Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom.

Discrete innervation of murine taste buds by peripheral taste neurons.

PubMed

Zaidi, Faisal N; Whitehead, Mark C

2006-08-09

The peripheral taste system likely maintains a specific relationship between ganglion cells that signal a particular taste quality and taste bud cells responsive to that quality. We have explored a measure of the receptoneural relationship in the mouse. By injecting single fungiform taste buds with lipophilic retrograde neuroanatomical markers, the number of labeled geniculate ganglion cells innervating single buds on the tongue were identified. We found that three to five ganglion cells innervate a single bud. Injecting neighboring buds with different color markers showed that the buds are primarily innervated by separate populations of geniculate cells (i.e., multiply labeled ganglion cells are rare). In other words, each taste bud is innervated by a population of neurons that only connects with that bud. Palate bud injections revealed a similar, relatively exclusive receptoneural relationship. Injecting buds in different regions of the tongue did not reveal a topographic representation of buds in the geniculate ganglion, despite a stereotyped patterned arrangement of fungiform buds as rows and columns on the tongue. However, ganglion cells innervating the tongue and palate were differentially concentrated in lateral and rostral regions of the ganglion, respectively. The principal finding that small groups of ganglion cells send sensory fibers that converge selectively on a single bud is a new-found measure of specific matching between the two principal cellular elements of the mouse peripheral taste system. Repetition of the experiments in the hamster showed a more divergent innervation of buds in this species. The results indicate that whatever taste quality is signaled by a murine geniculate ganglion neuron, that signal reflects the activity of cells in a single taste bud.

Vagal Sensory Innervation of the Gastric Sling Muscle and Antral Wall: Implications for GERD?

PubMed Central

Powley, Terry L.; Gilbert, Jared M.; Baronowsky, Elizabeth A.; Billingsley, Cherie N.; Martin, Felecia N.; Phillips, Robert J.

2012-01-01

Background The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Methods Sprague Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days post-injection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal were counterstained. Key Results The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with interstitial cells of Cajal. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings (IGLEs), the two types of mechanoreceptors found throughout stomach smooth muscle. Conclusions & Inferences The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors. PMID:22925069

Identified motor terminals in Drosophila larvae show distinct differences in morphology and physiology

NASA Technical Reports Server (NTRS)

Lnenicka, G. A.; Keshishian, H.

2000-01-01

In Drosophila, the type I motor terminals innervating the larval ventral longitudinal muscle fibers 6 and 7 have been the most popular preparation for combining synaptic studies with genetics. We have further characterized the normal morphological and physiological properties of these motor terminals and the influence of muscle size on terminal morphology. Using dye-injection and physiological techniques, we show that the two axons supplying these terminals have different innervation patterns: axon 1 innervates only muscle fibers 6 and 7, whereas axon 2 innervates all of the ventral longitudinal muscle fibers. This difference in innervation pattern allows the two axons to be reliably identified. The terminals formed by axons 1 and 2 on muscle fibers 6 and 7 have the same number of branches; however, axon 2 terminals are approximately 30% longer than axon 1 terminals, resulting in a corresponding greater number of boutons for axon 2. The axon 1 boutons are approximately 30% wider than the axon 2 boutons. The excitatory postsynaptic potential (EPSP) produced by axon 1 is generally smaller than that produced by axon 2, although the size distributions show considerable overlap. Consistent with vertebrate studies, there is a correlation between muscle fiber size and terminal size. For a single axon, terminal area and length, the number of terminal branches, and the number of boutons are all correlated with muscle fiber size, but bouton size is not. During prolonged repetitive stimulation, axon 2 motor terminals show synaptic depression, whereas axon 1 EPSPs facilitate. The response to repetitive stimulation appears to be similar at all motor terminals of an axon. Copyright 2000 John Wiley & Sons, Inc.

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

PubMed

Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

2015-04-16

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

Embryologic innervation of the rat laryngeal musculature--a model for investigation of recurrent laryngeal nerve reinnervation.

PubMed

Pitman, Michael J; Berzofsky, Craig E; Alli, Opeyemi; Sharma, Sansar

2013-12-01

Optimal management of vocal fold paralysis would entail recurrent laryngeal nerve (RLN) reinnervation resulting in normal vocal fold motion. Unfortunately, RLN reinnervation currently results in a nonfunctional vocal fold due to synkinetic reinnervation. Therapeutic interventions that guide regenerating axons back to the appropriate muscle would prevent synkinesis and restore vocal fold and glottal function. The initial step toward developing these therapies is the elucidation of the embryologic innervation of the larynx. This study aimed to identify the age of occurrence, timing, and pattern of embryologic innervation of the rat larynx, hypothesizing that differences in these parameters exist between distinct laryngeal muscles. Descriptive anatomic study. The larynx of rats aged embryologic day (E) 15, 16, 17, 19, and 21 were harvested and then sectioned. Two rats were used for each age. Sections were colabeled with neuronal class III β-tubulin polyclonal antibody to identify the presence of axons and alexa 488 conjugate α-bungarotoxin to identify the presence of motor endplates. The age at which axons and motor endplates were first present was noted. The position and pattern of the axons and motor endplates was recorded in relation to each other as well as the musculoskeletal anatomy of the larynx. The time at which axons appeared to innervate the medial thyroarytenoid (MTA) muscle, lateral thyroarytenoid (LTA) muscle, and the posterior cricoarytenoid (PCA) muscle was documented. Findings in the rat suggest the RLN reaches the larynx and begins branching by E15. Axons branch dorsally first and reach the PCA muscle before the other muscles. Branching toward the MTA muscle occurs only after axons have reached the LTA muscle. By E19, RLN axons have been guided to and selected their respective muscles with formation of neuromuscular junctions (NMJs) in the PCA, LTA and MTA muscles, though the formation of NMJs in the MTA muscle was comparatively delayed. This study describes the embryologic innervation of the rat larynx and suggests that there are distinct differences in the age of occurrence, timing, and pattern of innervation of the PCA, LTA, and MTA muscles of the rat. These findings lay the foundation for studies investigating the role of guidance cues in RLN axon guidance and the utility of these cues in the treatment of RLN injury via the stimulation of functional, nonsynkinetic reinnervation. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.

PubMed

Hoover, D B; Isaacs, E R; Jacques, F; Hoard, J L; Pagé, P; Armour, J A

2009-12-15

Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention.

Development of the intrinsic and extrinsic innervation of the gut.

PubMed

Uesaka, Toshihiro; Young, Heather M; Pachnis, Vassilis; Enomoto, Hideki

2016-09-15

The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract. Copyright © 2016 Elsevier Inc. All rights reserved.

Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion.

PubMed

Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D; Münzberg, Heike

2017-06-21

The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA GABA ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA GABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA GABA neurons that coexpress the neuropeptide galanin (LHA Gal ). These LHA Gal neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA Gal neurons may represent a subpopulation of LHA GABA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA Gal or LHA GABA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA Gal or LHA GABA neuronal activation both increased operant food-seeking behavior, but only activation of LHA GABA neurons increased overall chow consumption. Additionally, LHA Gal or LHA GABA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA GABA neurons induced compulsive-like locomotor behavior; while LHA Gal neurons induced locomotor activity without compulsivity. Thus, LHA Gal neurons define a subpopulation of LHA GABA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. SIGNIFICANCE STATEMENT The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHA GABA neurons is heterogeneous and largely undefined. Here we introduce LHA Gal neurons as a subset of LHA GABA neurons that lack direct innervation of the ventral tegmental area (VTA). LHA Gal neurons are sufficient to drive motivated feeding and locomotor activity similar to LHA GABA neurons, but without inducing compulsive-like behaviors, which we propose to require direct VTA innervation. Our study integrates galanin-expressing LHA neurons into our current understanding of the neuronal circuits and molecular mechanisms of the LHA that contribute to motivated feeding behaviors. Copyright © 2017 the authors 0270-6474/17/376053-13$15.00/0.

Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

PubMed

Proshchina, Alexandra E; Krivova, Yulia S; Barabanov, Valeriy M; Saveliev, Sergey V

2014-01-01

The ontogeny of the neuro-insular complexes (NIC) and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used double-staining with antibodies specific to pan-neural markers [neuron-specific enolase (NSE) and S100 protein] and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw) 10 onward. Later the density of S100 and NSE-positive fibers increased. In adults, this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onward. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained NIC and the number of these complexes was reduced in adults. The highest density of NIC is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

Ontogeny of Neuro-Insular Complexes and Islets Innervation in the Human Pancreas

PubMed Central

Proshchina, Alexandra E.; Krivova, Yulia S.; Barabanov, Valeriy M.; Saveliev, Sergey V.

2014-01-01

The ontogeny of the neuro-insular complexes (NIC) and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used double-staining with antibodies specific to pan-neural markers [neuron-specific enolase (NSE) and S100 protein] and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw) 10 onward. Later the density of S100 and NSE-positive fibers increased. In adults, this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onward. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained NIC and the number of these complexes was reduced in adults. The highest density of NIC is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis. PMID:24795697

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers.

PubMed

Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

2017-07-01

Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB- fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. Copyright © 2017. Published by Elsevier Inc.

Innervation pattern of the preocular human central retinal artery.

PubMed

Bergua, Antonio; Kapsreiter, Markus; Neuhuber, Winfried L; Reitsamer, Herbert A; Schrödl, Falk

2013-05-01

The central retinal artery (CRA) is the main vessel for inner retinal oxygen and nutrition supply. While the intraocular branches lack autonomic innervation, the innervation pattern of the extra-ocular part of this vessel along its course within the optic nerve is poorly investigated. This part however is essential for maintenance of retinal blood supply, in physiological and pathological conditions. Therefore, the aim of this study was the characterization of the autonomic innervation of the preocular CRA in humans with morphological methods. Meeting the Declaration of Helsinki, eyes of body or cornea donors were processed for single or double immunohistochemistry against tyrosine hydroxilase (TH), dopamine-β-hydroxylase (DBH), choline acetyl-transferase (ChAT), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), and cytochemistry for NADPH-diaphorase (NADPH-d). For documentation, light-, fluorescence-, and confocal laser-scanning microscopy were used. TH and DBH immunoreactive nerve fibres were detected in the CRA vessel wall, although a distinct perivascular plexus was missing. Further, nerve fibres immunoreactive for ChAT and VAChT were found, while CGRP, SP, and VIP were not detected. NADPH-d staining revealed scattered nerve fibres in the adventitia of the CRA and in close vicinity; however, nNOS-immunostaining could not confirm this finding. The CRA receives adrenergic and cholinergic innervations, indicating sympathetic and parasympathetic components, respectively. Remarkably, a peptidergic primary afferent innervation was missing. Since clinical results suggest an autoregulation of intraretinal vessels, further studies are needed to clarify the impact of CRA innervation for retinal perfusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

PubMed

Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

2011-09-14

Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain

PubMed Central

RUKHADZE, I.; KAMANI, H.; KUBIN, L.

2017-01-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N > GH > GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I > GH > N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70–120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes. PMID:22205596

Innervation of the anterior byssal retractor muscle in Mytilus edulis L. II. Ultrastructure of the glio-interstitial cells.

PubMed

Gilloteaux, J

1975-08-27

Studies on the intrinsic innervation of the anterior byssal retractor muscle (ABRM) in Mytilus edulis L. were continued at the ultrastructural level. Electron micrographs show nerve processes ensheathed by glio-interstitial cells running between muscle fibers. The glio-interstitial cells may represent all the types of osmiophilic cells previously described by the light microscopic ZIO technique in the anterior byssal retractor muscle.

Cell Class-Dependent Intracortical Connectivity and Output Dynamics of Layer 6 Projection Neurons of the Rat Primary Visual Cortex.

PubMed

Cotel, Florence; Fletcher, Lee N; Kalita-de Croft, Simon; Apergis-Schoute, John; Williams, Stephen R

2018-07-01

Neocortical information processing is powerfully influenced by the activity of layer 6 projection neurons through control of local intracortical and subcortical circuitry. Morphologically distinct classes of layer 6 projection neuron have been identified in the mammalian visual cortex, which exhibit contrasting receptive field properties, but little information is available on their functional specificity. To address this we combined anatomical tracing techniques with high-resolution patch-clamp recording to identify morphological and functional distinct classes of layer 6 projection neurons in the rat primary visual cortex, which innervated separable subcortical territories. Multisite whole-cell recordings in brain slices revealed that corticoclaustral and corticothalamic layer 6 projection neurons exhibited similar somatically recorded electrophysiological properties. These classes of layer 6 projection neurons were sparsely and reciprocally synaptically interconnected, but could be differentiated by cell-class, but not target-cell-dependent rules of use-dependent depression and facilitation of unitary excitatory synaptic output. Corticoclaustral and corticothalamic layer 6 projection neurons were differentially innervated by columnar excitatory circuitry, with corticoclaustral, but not corticothalamic, neurons powerfully driven by layer 4 pyramidal neurons, and long-range pathways conveyed in neocortical layer 1. Our results therefore reveal projection target-specific, functionally distinct, streams of layer 6 output in the rodent neocortex.

Central Somatosensory Networks Respond to a De Novo Innervated Penis: A Proof of Concept in Three Spina Bifida Patients.

PubMed

Kortekaas, Rudie; Nanetti, Luca; Overgoor, Max L E; de Jong, Bauke M; Georgiadis, Janniko R

2015-09-01

Spina bifida (SB) causes low spinal lesions, and patients often have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize sensation, sexuality and quality of life) is a surgical procedure whereby the penis is newly innervated using a sensory nerve originally targeting the inguinal area. Most TOMAX-treated SB patients initially experience penile stimulation as inguinal sensation, but eventually, the perception shifts to penis sensation with erotic feelings. The brain mechanisms mediating this perceptual shift, which are completely unknown, could hold relevance for understanding the brain's role in sexual development. The aim of this study was to study how a newly perceived penis would be mapped onto the brain after a lifelong disconnection. Three TOMAX-treated SB patients participated in a functional magnetic resonance imagery experiment while glans penis, inguinal area, and index finger were stimulated with a paint brush. Brush stimulation-induced activation of the primary somatosensory cortex (SI) and functional connectivity between SI and remote cerebral regions. Stimulation of the re-innervated side of the glans penis and the intact contralateral inguinal area activated a very similar location on SI. Yet, connectivity analysis identified distinct SI functional networks. In all three subjects, the middle cingulate cortex (MCC) and the parietal operculum-insular cortex (OIC) were functionally connected to SI activity during glans penis stimulation, but not to SI activity induced by inguinal stimulation. Investigating central somatosensory network activity to a de novo innervated penis in SB patients is feasible and informative. The consistent involvement of MCC and OIC above and beyond the brain network expected on the basis of inguinal stimulation suggests that these areas mediate the novel penis sensation in these patients. The potential role of MCC and OIC in this process is discussed, along with recommendations for further research. © 2015 International Society for Sexual Medicine.

Silent Damage of Noise on Cochlear Afferent Innervation in Guinea Pigs and the Impact on Temporal Processing

PubMed Central

He, Tingting; Aiken, Steve; Bance, Manohar; Yin, Shankai; Wang, Jian

2012-01-01

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs “silently” in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period. PMID:23185359

Identification of motor neurons and a mechanosensitive sensory neuron in the defecation circuitry of Drosophila larvae

PubMed Central

Zhang, Wei; Yan, Zhiqiang; Li, Bingxue; Jan, Lily Yeh; Jan, Yuh Nung

2014-01-01

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca2+ imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction. DOI: http://dx.doi.org/10.7554/eLife.03293.001 PMID:25358089

Synaptic Targets of Medial Septal Projections in the Hippocampus and Extrahippocampal Cortices of the Mouse

PubMed Central

Joshi, Abhilasha; Viney, Tim J.; Kis, Viktor

2015-01-01

Temporal coordination of neuronal assemblies among cortical areas is essential for behavioral performance. GABAergic projections from the medial septum and diagonal band complex exclusively innervate GABAergic interneurons in the rat hippocampus, contributing to the coordination of neuronal activity, including the generation of theta oscillations. Much less is known about the synaptic target neurons outside the hippocampus. To reveal the contribution of synaptic circuits involving the medial septum of mice, we have identified postsynaptic cortical neurons in wild-type and parvalbumin-Cre knock-in mice. Anterograde axonal tracing from the septum revealed extensive innervation of the hippocampus as well as the subiculum, presubiculum, parasubiculum, the medial and lateral entorhinal cortices, and the retrosplenial cortex. In all examined cortical regions, many septal GABAergic boutons were in close apposition to somata or dendrites immunopositive for interneuron cell-type molecular markers, such as parvalbumin, calbindin, calretinin, N-terminal EF-hand calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules. Electron microscopic observations revealed septal boutons forming axosomatic or axodendritic type II synapses. In the CA1 region of hippocampus, septal GABAergic projections exclusively targeted interneurons. In the retrosplenial cortex, 93% of identified postsynaptic targets belonged to interneurons and the rest to pyramidal cells. These results suggest that the GABAergic innervation from the medial septum and diagonal band complex contributes to temporal coordination of neuronal activity via several types of cortical GABAergic interneurons in both hippocampal and extrahippocampal cortices. Oscillatory septal neuronal firing at delta, theta, and gamma frequencies may phase interneuron activity. SIGNIFICANCE STATEMENT Diverse types of GABAergic interneurons coordinate the firing of cortical principal cells required for memory processes. During wakefulness and rapid eye movement sleep, the rhythmic firing of cortical GABAergic neurons plays a key role in governing network activity. We investigated subcortical GABAergic projections in the mouse that extend from the medial septum/diagonal band nuclei to GABAergic neurons in the hippocampus and related extrahippocampal cortical areas, including the medial entorhinal cortex. These areas contribute to navigation and show theta rhythmic activity. We found selective GABAergic targeting of different groups of cortical GABAergic neurons, immunoreactive for combinations of cell-type markers. As septal GABAergic neurons also fire rhythmically, their selective innervation of cortical GABAergic neurons suggests an oscillatory synchronization of neuronal activity across functionally related areas. PMID:26631464

Islet organogenesis, angiogenesis and innervation.

PubMed

Cerf, Marlon E

2011-11-01

The pancreas is characterized by a major component, an exocrine and ductal system involved in digestion, and a minor component, the endocrine islets represented by islet micro-organs that tightly regulate glucose homoeostasis. Pancreatic organogenesis is strictly co-ordinated by transcription factors that are expressed sequentially to yield functional islets capable of maintaining glucose homoeostasis. Angiogenesis and innervation complete islet development, equipping islets to respond to metabolic demands. Proper regulation of this triad of processes during development is critical for establishing functional islets.

The Role of Basal Forebrain in Rat Somatosensory Cortex: Impact on Cholinergic Innervation, Sensory Information Processing, and Tactile Discrimination

DTIC Science & Technology

1993-05-28

1993 Dissertation and Abstract Approved: Commit tee Chairperson . ,a..w ember ~tee Member tli:u., ;2 9" PQ3 bate Date bate The author...1982; Mesulam et al., 1983; Rye et al., 1984; Saper, 1984). I will refer to the region of the basal forebrain that supplies cholinergic innervation to...topographical organization has been observed for cholinergic projection patterns, with more rostral and medial basal forebrain cell groups supplying

Auditory hair cell innervational patterns in lizards.

PubMed

Miller, M R; Beck, J

1988-05-22

The pattern of afferent and efferent innervation of two to four unidirectional (UHC) and two to nine bidirectional (BHC) hair cells of five different types of lizard auditory papillae was determined by reconstruction of serial TEM sections. The species studies were Crotaphytus wislizeni (iguanid), Podarcis (Lacerta) sicula and P. muralis (lacertids), Ameiva ameiva (teiid), Coleonyx variegatus (gekkonid), and Mabuya multifasciata (scincid). The main object was to determine in which species and in which hair cell types the nerve fibers were innervating only one (exclusive innervation), or two or more hair cells (nonexclusive innervation); how many nerve fibers were supplying each hair cell; how many synapses were made by the innervating fibers; and the total number of synapses on each hair cell. In the species studies, efferent innervation was limited to the UHC, and except for the iguanid, C. wislizeni, it was nonexclusive, each fiber supplying two or more hair cells. Afferent innervation varied both with the species and the hair cell types. In Crotaphytus, both the UHC and the BHC were exclusively innervated. In Podarcis and Ameiva, the UHC were innervated exclusively by some fibers but nonexclusively by others (mixed pattern). In Coleonyx, the UHC were exclusively innervated but the BHC were nonexclusively innervated. In Mabuya, both the UHC and BHC were nonexclusively innervated. The number of afferent nerve fibers and the number of afferent synapses were always larger in the UHC than in the BHC. In Ameiva, Podarcis, and Mabuya, groups of bidirectionally oriented hair cells occur in regions of cytologically distinct UHC, and in Ameiva, unidirectionally oriented hair cells occur in cytologically distinct BHC regions.

Rhythmically Active Enkephalin-Expressing GABAergic Cells in the CA1 Area of the Hippocampus Project to the Subiculum and Preferentially Innervate Interneurons

PubMed Central

Fuentealba, Pablo; Tomioka, Ryohei; Dalezios, Yannis; Márton, László F.; Studer, Michele; Rockland, Kathleen; Klausberger, Thomas; Somogyi, Peter

2015-01-01

Enkephalins (ENKs) are endogenous opioids that regulate synaptic excitability of GABAergic networks in the cerebral cortex. Using retrograde tracer injections in the subiculum, we identified a hippocampal population of ENK-expressing projection neurons. In situ hybridization for GAD shows that ENK-expressing cells are a small GABAergic subpopulation. Furthermore, by extracellular recording and juxtacellular labeling in vivo, we identified an ENK-expressing cell in stratum radiatum of the CA1 area by its complete axodendritic arborization and characteristic spike timing during network oscillations. The somatodendritic membrane was immunopositive for mGluR1α, and there was both a rich local axon in CA1 and subicular-projecting branches. The boutons showed cell-type- and layer-specific innervation, i.e., interneurons were the main targets in the alveus, both interneurons and pyramidal cell dendrites were innervated in the other layers, and interneurons were exclusive targets in the subiculum. Parvalbumin-, but not somatostatin-, calbindin-, or cholecystokinin-expressing interneurons were preferred synaptic targets. During network activity, the juxtacellularly labeled ENK-expressing cell was phase modulated throughout theta oscillations, but silenced during sharp-wave/ripple episodes. After these episodes the interneuron exhibited rebound activity of high-frequency spike bursts, presumably causing peptide release. The ENK-expressing interneurons innervating parvalbumin-positive interneurons might contribute to the organization of the sharp-wave/ripple episodes by decreased firing during and rebound activity after the ripple episodes, as well as to the coordination of activity between the CA1 and subicular areas during network oscillations. PMID:18829959

The structural and functional differentiation of hair cells in a lizard’s basilar papilla suggests an operational principle of amniote cochleas

PubMed Central

Chiappe, M. Eugenia; Kozlov, Andrei S.; Hudspeth, A. J.

2007-01-01

The hair cells in the mammalian cochlea are of two distinct types. Inner hair cells are responsible for transducing mechanical stimuli into electrical responses, which they forward to the brain through a copious afferent innervation. Outer hair cells, which are thought to mediate the active process that sensitizes and tunes the cochlea, possess a negligible afferent innervation. For every inner hair cell there are approximately three outer hair cells, so only a quarter of the hair cells directly deliver information to the central nervous system. Although this is a surprising feature for a sensory system, the occurrence of a similar innervation pattern in birds and crocodilians suggests that the arrangement has an adaptive value. Using a lizard with highly developed hearing, the tokay gecko, we demonstrate in the present study that the same principle operates in a third major group of terrestrial animals. We propose that the differentiation of hair cells into signaling and amplifying classes reflects incompatible strategies for the optimization of mechanoelectrical transduction and of an active process based on active hair-bundle motility. PMID:17978038

Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.

PubMed

Barry, Christine M; Ji, Esther; Sharma, Harman; Beukes, Lara; Vilimas, Patricia I; DeGraaf, Yvette C; Matusica, Dusan; Haberberger, Rainer V

2017-07-01

The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall. We compared cervical and vulvar areas of the vagina in young nullipara and older multipara C57Bl/6 mice, and identified differences including that small ganglia were restricted to cervical segments, epithelial fibers were mainly present in vulvar segments and most nerve fibers were found in the lamina propria of the cervical region of the vagina, where a higher number of fibers containing immunoreactivity for VIP, CGRP, SP, or nNOS were found. Two populations of VIP-containing fibers were identified: fibers containing CGRP and fibers containing VIP but not CGRP. Differences between young and older mice were present in multiple layers of the vaginal wall, with older mice showing overall loss of innervation of epithelium of the proximal vagina and reduced proportions of VIP, CGRP, and SP containing nerve fibers in the distal epithelium. The distal vagina also showed increased vascularization and perivascular fibers containing NPY. Immunolabeling of ganglia associated with the vagina indicated the likely origin of some peptidergic fibers. Our results reveal regional differences and age- or parity-related changes in innervation of the mouse vagina, effecting the distribution of neuropeptides with diverse roles in function of the female genital tract. © 2017 Wiley Periodicals, Inc.

Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene.

PubMed

Mabe, Abigail M; Hoard, Jennifer L; Duffourc, Michelle M; Hoover, Donald B

2006-10-01

Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown. We have therefore evaluated NRTN expression in adult mouse heart and the association of NRTN receptors with intracardiac cholinergic neurons and nerve fibers. Mapping the regional distribution and density of cholinergic nerves in mouse heart was an integral part of this goal. Analysis of RNA from adult C57BL/6 mouse hearts demonstrated NRTN expression in atrial and ventricular tissue. Virtually all neurons in the cardiac parasympathetic ganglia exhibited the cholinergic phenotype, and over 90% of these cells contained both components of the NRTN receptor, Ret tyrosine kinase and GDNF family receptor alpha2 (GFRalpha2). Cholinergic nerve fibers, identified by labeling for the high affinity choline transporter, were abundant in the sinus and atrioventricular nodes, ventricular conducting system, interatrial septum, and much of the right atrium, but less abundant in the left atrium. The right ventricular myocardium contained a low density of cholinergic nerves, which were sparse in other regions of the working ventricular myocardium. Some cholinergic nerves were also associated with coronary vessels. GFRalpha2 was present in most cholinergic nerve fibers and in Schwann cells and their processes throughout the heart. Some cholinergic nerve fibers, such as those in the sinus node, also exhibited Ret immunoreactivity. These findings provide the first detailed mapping of cholinergic nerves in mouse heart and suggest that the neurotrophic influence of NRTN on cardiac cholinergic innervation continues in mature animals.

Anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits.

PubMed

Cruz, Yolanda; Hernández-Plata, Isela; Lucio, Rosa Angélica; Zempoalteca, René; Castelán, Francisco; Martínez-Gómez, Margarita

2017-09-01

To determine the anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits. Chinchilla adult anesthetized female rabbits were used. Anatomical, electrophysiological, and histological studies were performed. L7, S1, and some fibers from S2 and S3 form the lumbosacral trunk, which gives origin to the sciatic nerve and innervation to the gluteal region. From S2 to S3 originates the pudendal nerve, whose branches innervates the striated anal and urethra sphincters, as well as the bulbospongiosus, ischiocavernosus, and constrictor vulvae muscles. The sensory field of the pudendal nerve is ∼1800 mm 2 and is localized in the clitoral sheath and perineal and perigenital skin. The organization of the pudendal nerve varies between individuals, three patterns were identified, and one of them was present in 50% of the animals. From S3 emerge the pelvic nerve, which anastomoses to form a plexus localized between the vagina and the rectum. The innervation of the pelvic floor originates from S3 to S4 fibers. Most of the sacral spinal nerves of rabbit are mixed, carrying sensory, and motor information. Sacral nerves innervate the hind limbs, pelvic viscera, clitoris, perineal muscles, inguinal and anal glands and perineal, perigenital, and rump skin. The detailed description of the sacral nerves organization, topography, and axonal components further the knowledge of the innervation in pelvic and perinal structures of the female rabbit. This information will be useful in future studies about the physiology and physiopathology of urinary, fecal, reproductive, and sexual functions. © 2017 Wiley Periodicals, Inc.

A Sympathetic Neuron Autonomous Role for Egr3-Mediated Gene Regulation in Dendrite Morphogenesis and Target Tissue Innervation

PubMed Central

Quach, David H.; Oliveira-Fernandes, Michelle; Gruner, Katherine A.; Tourtellotte, Warren G.

2013-01-01

Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development. Mice lacking Egr3 in the germline have sympathetic target tissue innervation abnormalities and physiologic sympathetic dysfunction similar to humans with dysautonomia. However, since Egr3 is widely expressed and has pleiotropic function, it has not been clear whether it has a role within sympathetic neurons and if so, what target genes it regulates to facilitate target tissue innervation. Here, we show that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with NGF and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. Microarray analysis performed on sympathetic neurons identified many target genes deregulated in the absence of Egr3, with some of the most significantly deregulated genes having roles in axonogenesis, dendritogenesis, and axon guidance. Using a novel genetic technique to visualize axons and dendrites in a subpopulation of randomly labeled sympathetic neurons, we found that Egr3 has an essential role in regulating sympathetic neuron dendrite morphology and terminal axon branching, but not in regulating sympathetic axon guidance to their targets. Together, these results indicate that Egr3 has a sympathetic neuron autonomous role in sympathetic nervous system development that involves modulating downstream target genes affecting the outgrowth and branching of sympathetic neuron dendrites and axons. PMID:23467373

Three-dimensional reconstruction of the cranial and anterior spinal nerves in early tadpoles of Xenopus laevis (Pipidae, Anura).

PubMed

Naumann, Benjamin; Olsson, Lennart

2018-04-01

Xenopus laevis is one of the most widely used model organism in neurobiology. It is therefore surprising, that no detailed and complete description of the cranial nerves exists for this species. Using classical histological sectioning in combination with fluorescent whole mount antibody staining and micro-computed tomography we prepared a detailed innervation map and a freely-rotatable three-dimensional (3D) model of the cranial nerves and anterior-most spinal nerves of early X. laevis tadpoles. Our results confirm earlier descriptions of the pre-otic cranial nerves and present the first detailed description of the post-otic cranial nerves. Tracing the innervation, we found two previously undescribed head muscles (the processo-articularis and diaphragmatico-branchialis muscles) in X. laevis. Data on the cranial nerve morphology of tadpoles are scarce, and only one other species (Discoglossus pictus) has been described in great detail. A comparison of Xenopus and Discoglossus reveals a relatively conserved pattern of the post-otic and a more variable morphology of the pre-otic cranial nerves. Furthermore, the innervation map and the 3D models presented here can serve as an easily accessible basis to identify alterations of the innervation produced by experimental studies such as genetic gain- and loss of function experiments. © 2017 Wiley Periodicals, Inc.

Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult Virgin Rats: A Histological Study.

PubMed

Li, Ting; Ma, Yuanyuan; Zhang, Hong; Yan, Ping; Huo, Lili; Hu, Yongyan; Chen, Xi; Li, Ting; Zhang, Miao; Liu, Zhaohui

2017-01-01

Background . Our previous Gräfenberg spot findings confirmed that the distal-third areas of the anterior vaginal wall bore a significantly greater number of nerves and sexual hormone may have certain degree of influence on these significant differences. However, the role of estrogen in vaginal innervations remains controversial. Methods . To investigate whether hormonal-neural interactions occur in the vagina, sixty rats were randomly divided into six groups: Sham-operated, ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry. Results . The density of small nerve fibers was significantly higher in the distal-half areas of intact vaginal walls than the proximal-half areas ( P = 0.001). In contrast, the overall PGP 9.5-ir fiber innervation density was significantly decreased in the OVX rats subjected to surgical menopause. Sustained estrogen administration for 2 weeks resulted in nerve fiber proliferation, with values reaching normal levels in the low-dose estradiol valerate group. Conclusion . Our findings indicate that systemic hormonal therapy with low-dose estradiol valerate is effective and safe for treating deficient vaginal innervation caused by low level of estrogen activity in menopausal women and may aid studies to identify an optimal estradiol dose to provide relief from vaginal discomfort.

Three-dimensional analysis of vestibular efferent neurons innervating semicircular canals of the gerbil

NASA Technical Reports Server (NTRS)

Purcell, I. M.; Perachio, A. A.

1997-01-01

Anterograde labeling techniques were used to examine peripheral innervation patterns of vestibular efferent neurons in the crista ampullares of the gerbil. Vestibular efferent neurons were labeled by extracellular injections of biocytin or biotinylated dextran amine into the contralateral or ipsilateral dorsal subgroup of efferent cell bodies (group e) located dorsolateral to the facial nerve genu. Anterogradely labeled efferent terminal field varicosities consist mainly of boutons en passant with fewer of the terminal type. The bouton swellings are located predominately in apposition to the basolateral borders of the afferent calyces and type II hair cells, but several boutons were identified close to the hair cell apical border on both types. Three-dimensional reconstruction and morphological analysis of the terminal fields from these cells located in the sensory neuroepithelium of the anterior, horizontal, and posterior cristae were performed. We show that efferent neurons densely innervate each end organ in widespread terminal fields. Subepithelial bifurcations of parent axons were minimal, with extensive collateralization occurring after the axons penetrated the basement membrane of the neuroepithelium. Axonal branching ranged between the 6th and 27th orders and terminal field collecting area far exceeds that of the peripheral terminals of primary afferent neurons. The terminal fields of the efferent neurons display three morphologically heterogeneous types: central, peripheral, and planum. All cell types possess terminal fields displaying a high degree of anisotropy with orientations typically parallel to or within +/-45 degrees of the longitudinal axis if the crista. Terminal fields of the central and planum zones predominately project medially toward the transverse axis from the more laterally located penetration of the basement membrane by the parent axon. Peripheral zone terminal fields extend predominately toward the planum semilunatum. The innervation areas of efferent terminal fields display a trend from smallest to largest for the central, peripheral, and planum types, respectively. Neurons that innervate the central zone of the crista do not extend into the peripheral or planum regions. Conversely, those neurons with terminal fields in the peripheral or planum regions do not innervate the central zone of the sensory neuroepithelium. The central zone of the crista is innervated preferentially by efferent neurons with cell bodies located in the ipsilateral group e. The peripheral and planum zones of the crista are innervated preferentially by efferent neurons with cell bodies located in the contralateral group e. A model incorporating our anatomic observations is presented describing an ipsilateral closed-loop feedback between ipsilateral efferent neurons and the periphery and an open-loop feed-forward innervation from contralateral efferent neurons. A possible role for the vestibular efferent neurons in the modulation of semicircular canal afferent response dynamics is proposed.

Excitatory glutamate is essential for development and maintenance of the piloneural mechanoreceptor.

PubMed

Woo, Seung-Hyun; Baba, Yoshichika; Franco, Alexa M; Lumpkin, Ellen A; Owens, David M

2012-02-01

The piloneural collar in mammalian hairy skin comprises an intricate pattern of circumferential and longitudinal sensory afferents that innervate primary and secondary pelage hairs. The longitudinal afferents tightly associate with terminal Schwann cell processes to form encapsulated lanceolate nerve endings of rapidly adapting mechanoreceptors. The molecular basis for piloneural development, maintenance and function is poorly understood. Here, we show that Nefh-expressing glutamatergic neurons represent a major population of longitudinal and circumferential sensory afferents innervating the piloneural collar. Our findings using a VGLUT2 conditional-null mouse model indicate that glutamate is essential for innervation, patterning and differentiation of NMDAR(+) terminal Schwann cells during piloneural collar development. Similarly, treatment of adult mice with a selective NMDAR antagonist severely perturbed piloneural collar structure and reduced excitability of these mechanosensory neurons. Collectively, these results show that DRG-derived glutamate is essential for the proper development, maintenance and sensory function of the piloneural mechanoreceptor.

Innervation of single fungiform taste buds during development in rat.

PubMed

Krimm, R F; Hill, D L

1998-08-17

To determine whether the innervation of taste buds changes during postnatal development, the number of geniculate ganglion cells that innervated single fungiform taste buds were quantified in the tip- and midregions of the tongue of adult and developing rats. There was substantial variation in both the size of individual taste buds and number of geniculate ganglion cells that innervated them. Importantly, taste bud morphology and innervation were highly related. Namely, the number of labeled geniculate ganglion cells that innervated a taste bud was highly correlated with the size of the taste bud (r = 0.91, P < .0003): The larger the taste bud, the more geniculate ganglion cells that innervated it. The relationship between ganglion cell number and taste bud volume emerged during the first 40 days postnatal. Whereas there was no difference in the average number of ganglion cells that innervated individual taste buds in rats aged 10 days postnatal through adulthood, taste bud volumes increased progressively between 10 and 40 days postnatal, at which age taste bud volumes were similar to adults. The maturation of taste bud size was accompanied by the emergence of the relationship between taste bud volume and number of innervating neurons. Specifically, there was no correlation between taste bud size and number of innervating geniculate ganglion cells in 10-, 20-, or 30-day-old rats, whereas taste bud size and the number of innervating ganglion cells in 40-day-old rats were positively correlated (r = .80, P < .002). Therefore, the relationship between taste bud size and number of innervating ganglion cells develops over a prolonged postnatal period and is established when taste buds grow to their adult size.

Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

PubMed Central

Damico, J.P.; Ervolino, E.; Torres, K.R.; Batagello, D.S.; Cruz-Rizzolo, R.J.; Casatti, C.A.; Bauer, J.A.

2012-01-01

The aim of this study was to identify immunoreactive neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) neurons in the autonomic and sensory ganglia, specifically neurons that innervate the rat temporomandibular joint (TMJ). A possible variation between the percentages of these neurons in acute and chronic phases of carrageenan-induced arthritis was examined. Retrograde neuronal tracing was combined with indirect immunofluorescence to identify NPY-immunoreactive (NPY-IR) and CGRP- immunoreactive (CGRP-IR) neurons that send nerve fibers to the normal and arthritic temporomandibular joint. In normal joints, NPY-IR neurons constitute 78±3%, 77±6% and 10±4% of double-labeled nucleated neuronal profile originated from the superior cervical, stellate and otic ganglia, respectively. These percentages in the sympathetic ganglia were significantly decreased in acute (58±2% for superior cervical ganglion and 58±8% for stellate ganglion) and chronic (60±2% for superior cervical ganglion and 59±15% for stellate ganglion) phases of arthritis, while in the otic ganglion these percentages were significantly increased to 19±5% and 13±3%, respectively. In the trigeminal ganglion, CGRP-IR neurons innervating the joint significantly increased from 31±3% in normal animals to 54±2% and 49±3% in the acute and chronic phases of arthritis, respectively. It can be concluded that NPY neurons that send nerve fibers to the rat temporomandibular joint are located mainly in the superior cervical, stellate and otic ganglia. Acute and chronic phases of carrageenan-induced arthritis lead to an increase in the percentage of NPY-IR parasympathetic and CGRP-IR sensory neurons and to a decrease in the percentage of NPY-IR sympathetic neurons related to TMJ innervation. PMID:23027347

Afferent innervation of the utricular macula in pigeons

NASA Technical Reports Server (NTRS)

Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

2003-01-01

Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were located in the extrastriola. The cellular organization and innervation patterns of the utricular maculae in birds appear to represent an organ in adaptive evolution, different from that observed for amphibians or mammals.

Heart Development, Diseases, and Regeneration　- New Approaches From Innervation, Fibroblasts, and Reprogramming.

PubMed

Ieda, Masaki

2016-09-23

It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

L-acetylcarnitine enhances functional muscle re-innervation.

PubMed

Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

1991-01-01

The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

Neuromuscular partitioning in the extensor carpi radialis longus and brevis based on intramuscular nerve distribution patterns: A three-dimensional modeling study.

PubMed

Ravichandiran, Mayoorendra; Ravichandiran, Nisanthini; Ravichandiran, Kajeandra; McKee, Nancy H; Richardson, Denyse; Oliver, Michele; Agur, Anne M

2012-04-01

Differential activation of specific regions within a skeletal muscle has been linked to the presence of neuromuscular compartments. However, few studies have investigated the extra- or intramuscular innervation throughout the muscle volume of extensor carpi radialis longus (ECRL) and brevis (ECRB). The aim of this study was to determine the presence of neuromuscular partitions in ECRL and ECRB based on the extra- and intramuscular innervation using three-dimensional modeling. The extra- and intramuscular nerve distribution was digitized and reconstructed in 3D in all the muscle volumes using Autodesk Maya in seven formalin embalmed cadaveric specimens (mean age, 75.7 ± 15.2 years). The intramuscular nerve distribution was modeled in all the muscle volumes. ECRL was found to have two neuromuscular compartments, superficial and deep. One branch from the radial nerve proper was found to innervate ECRL. This branch was divided into anterior and posterior branches to the superficial and deep compartments, respectively. Five innervation patterns were identified in ECRB with partitioning of the muscle belly into two, three, or four compartments, in a proximal to distal direction depending on the number of nerve branches entering the muscle belly. The ECRL and ECRB both demonstrated neuromuscular compartmentalization based on intramuscular innervation. According to the partitioning hypothesis, a muscle may be differentially activated depending on the required function of the muscle, thus allowing multifunctional muscles to contribute to a variety of movements. Therefore, the increased number of neuromuscular partitions in ECRB when compared with ECRL could be due to the need for more differential recruitment in the ECRB depending on force requirements. Copyright © 2011 Wiley Periodicals, Inc.

Spatiotemporal definition of neurite outgrowth, refinement and retraction in the developing mouse cochlea.

PubMed

Huang, Lin-Chien; Thorne, Peter R; Housley, Gary D; Montgomery, Johanna M

2007-08-01

The adult mammalian cochlea receives dual afferent innervation: the inner sensory hair cells are innervated exclusively by type I spiral ganglion neurons (SGN), whereas the sensory outer hair cells are innervated by type II SGN. We have characterized the spatiotemporal reorganization of the dual afferent innervation pattern as it is established in the developing mouse cochlea. This reorganization occurs during the first postnatal week just before the onset of hearing. Our data reveal three distinct phases in the development of the afferent innervation of the organ of Corti: (1) neurite growth and extension of both classes of afferents to all hair cells (E18-P0); (2) neurite refinement, with formation of the outer spiral bundles innervating outer hair cells (P0-P3); (3) neurite retraction and synaptic pruning to eliminate type I SGN innervation of outer hair cells, while retaining their innervation of inner hair cells (P3-P6). The characterization of this developmental innervation pattern was made possible by the finding that tetramethylrhodamine-conjugated dextran (TMRD) specifically labeled type I SGN. Peripherin and choline-acetyltransferase immunofluorescence confirmed the type II and efferent innervation patterns, respectively, and verified the specificity of the type I SGN neurites labeled by TMRD. These findings define the precise spatiotemporal neurite reorganization of the two afferent nerve fiber populations in the cochlea, which is crucial for auditory neurotransmission. This reorganization also establishes the cochlea as a model system for studying CNS synapse development, plasticity and elimination.

Factors Regulating Vagal Sensory Development: Potential Role in Obesities of Developmental Origin

PubMed Central

Fox, Edward A.; Murphy, Michelle C.

2008-01-01

Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition preor postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development. PMID:18234244

Reflex regulation of airway sympathetic nerves in guinea-pigs

PubMed Central

Oh, Eun Joo; Mazzone, Stuart B; Canning, Brendan J; Weinreich, Daniel

2006-01-01

Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance P-containing capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1–T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10–60 μm) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μm, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway contraction induced by parasympathetic nerve activation in the airways. PMID:16581869

SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

PubMed Central

Gulbransen, Brian; Silver, Wayne; Finger, Tom

2008-01-01

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

Defective pulmonary innervation and autonomic imbalance in congenital diaphragmatic hernia

PubMed Central

Lath, Nikesh R.; Galambos, Csaba; Rocha, Alejandro Best; Malek, Marcus; Gittes, George K.

2012-01-01

Congenital diaphragmatic hernia (CDH) is associated with significant mortality due to lung hypoplasia and pulmonary hypertension. The role of embryonic pulmonary innervation in normal lung development and lung maldevelopment in CDH has not been defined. We hypothesize that developmental defects of intrapulmonary innervation, in particular autonomic innervation, occur in CDH. This abnormal embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. To define patterns of pulmonary innervation in CDH, human CDH and control lung autopsy specimens were stained with the pan-neural marker S-100. To further characterize patterns of overall and autonomic pulmonary innervation during lung development in CDH, the murine nitrofen model of CDH was utilized. Immunostaining for protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (a sympathetic marker), vesicular acetylcholine transporter (a parasympathetic marker), or VIP (a parasympathetic marker) was performed on lung whole mounts and analyzed via confocal microscopy and three-dimensional reconstruction. Peribronchial and perivascular neuronal staining pattern is less complex in human CDH than control lung. In mice, protein gene product 9.5 staining reveals less complex neuronal branching and decreased neural tissue in nitrofen-treated lungs from embryonic day 12.5 to 16.5 compared with controls. Furthermore, nitrofen-treated embryonic lungs exhibited altered autonomic innervation, with a relative increase in sympathetic nerve staining and a decrease in parasympathetic nerve staining compared with controls. These results suggest a primary defect in pulmonary neural developmental in CDH, resulting in less complex neural innervation and autonomic imbalance. Defective embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. PMID:22114150

Molecular Basis of Infrared Detection by Snakes

PubMed Central

Gracheva, Elena O.; Ingolia, Nicolas T.; Kelly, Yvonne M.; Cordero-Morales, Julio F.; Hollopeter, Gunther; Chesler, Alexander T.; Sánchez, Elda E.; Perez, John C.; Weissman, Jonathan S.; Julius, David

2010-01-01

Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a ‘thermal image’ of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibers of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibers that innervate the pit organ. TRPA1 orthologues from pit bearing snakes (vipers, pythons, and boas) are the most heat sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of TRP channels as thermosensors in the vertebrate nervous system. PMID:20228791

Morphology and innervation of the vestibular lagena in pigeons

PubMed Central

Mridha, Zakir; Wu, Le-Qing; Dickman, J. David

2012-01-01

The morphological characteristics of the pigeon lagena were examined using histology, scanning electron microscopy, and biotinylated dextran amine (BDA) neural tracers. The lagena epithelium was observed to lie partially in a parasagittal plane, but was also U-shaped with orthogonal (lateral) directed tips. Hair cell planar polarities were oriented away from a central reversal line that ran nearly the length of the epithelium. Similar to the vertebrate utricle and saccule, three afferent classes were observed based upon their terminal innervation pattern, which include calyx, dimorph, and bouton fibers. Calyx and dimorph afferents innervated the striola region of the lagena, while bouton afferents innervated the extrastriola and a small region of the central striola known as the type II band. Calyx units had large calyceal terminal structures that innervated only type I hair cells. Dimorph afferents innervated both type I and II hair cells, with calyx and bouton terminals. Bouton afferents had the largest most complex innervation patterns and the greatest terminal areas contacting many hair cells. PMID:22387112

Solitary chemoreceptor cell survival is independent of intact trigeminal innervation.

PubMed

Gulbransen, Brian; Silver, Wayne; Finger, Thomas E

2008-05-01

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al. [2003] Proc Natl Acad Sci USA 100:8981-8986). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al. [2003]) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. (c) 2008 Wiley-Liss, Inc.

Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells

PubMed Central

Ji, Young Rae; Warrier, Sunita; Jiang, Tao

2018-01-01

The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets. PMID:29671737

Dynamic Expression of Serotonin Receptor 5-HT3A in Developing Sensory Innervation of the Lower Urinary Tract

PubMed Central

Ritter, K. Elaine; Southard-Smith, E. Michelle

2017-01-01

Sensory afferent signaling is required for normal function of the lower urinary tract (LUT). Despite the wide prevalence of bladder dysfunction and pelvic pain syndromes, few effective treatment options are available. Serotonin receptor 5-HT3A is a known mediator of visceral afferent signaling and has been implicated in bladder function. However, basic expression patterns for this gene and others among developing bladder sensory afferents that could be used to inform regenerative efforts aimed at treating deficiencies in pelvic innervation are lacking. To gain greater insight into the molecular characteristics of bladder sensory innervation, we conducted a thorough characterization of Htr3a expression in developing and adult bladder-projecting lumbosacral dorsal root ganglia (DRG) neurons. Using a transgenic Htr3a-EGFP reporter mouse line, we identified 5-HT3A expression at 10 days post coitus (dpc) in neural crest derivatives and in 12 dpc lumbosacral DRG. Using immunohistochemical co-localization we observed Htr3a-EGFP expression in developing lumbosacral DRG that partially coincides with neuropeptides CGRP and Substance P and capsaicin receptor TRPV1. A majority of Htr3a-EGFP+ DRG neurons also express a marker of myelinated Aδ neurons, NF200. There was no co-localization of 5-HT3A with the TRPV4 receptor. We employed retrograde tracing in adult Htr3a-EGFP mice to quantify the contribution of 5-HT3A+ DRG neurons to bladder afferent innervation. We found that 5-HT3A is expressed in a substantial proportion of retrograde traced DRG neurons in both rostral (L1, L2) and caudal (L6, S1) axial levels that supply bladder innervation. Most bladder-projecting Htr3a-EGFP+ neurons that co-express CGRP, Substance P, or TRPV1 are found in L1, L2 DRG, whereas Htr3a-EGFP+, NF200+ bladder-projecting neurons are from the L6, S1 axial levels. Our findings contribute much needed information regarding the development of LUT innervation and highlight the 5-HT3A serotonin receptor as a candidate for future studies of neurally mediated bladder control. PMID:28111539

Dual Innervation of Neonatal Merkel Cells in Mouse Touch Domes

PubMed Central

Luo, Wenqin

2014-01-01

Merkel cell-neurite complexes are specialized mechanosensory end organs that mediate discriminative touch sensation. It is well established that type I slowly adapting (SAI) mechanoreceptors, which express neural filament heavy chain (NFH), innervate Merkel cells. It was previously shown that neurotrophic factor NT3 and its receptor TrkC play crucial roles in controlling touch dome Merkel cell innervation of NFH+ fibers. In addition, nerve fibers expressing another neurotrophic tyrosine receptor kinase (NTRK), Ret, innervate touch dome Merkel cells as well. However, the relationship between afferents responsive to NT3/TrkC signaling and those expressing Ret is unclear. It is also controversial if these Ret+ fibers belong to the early or late Ret+ DRG neurons, which are defined based on the co-expression and developmental dependence of TrkA. To address these questions, we genetically traced Ret+ and TrkC+ fibers and analyzed their developmental dependence on TrkA. We found that Merkel cells in neonatal mouse touch domes receive innervation of two types of fibers: one group is Ret+, while the other subset expresses TrkC and NFH. In addition, Ret+ fibers depend on TrkA for their survival and normal innervation whereas NFH+ Merkel cell innervating fibers are almost unaltered in TrkA mutant mice, supporting that Ret+ and NFH+/TrkC+ afferents are two distinct groups. Ret signaling, on the other hand, plays a minor role for the innervation of neonatal touch domes. In contrast, Merkel cells in the glabrous skin are mainly contacted by NFH+/TrkC+ afferents. Taken together, our results suggest that neonatal Merkel cells around hair follicles receive dual innervation while Merkel cells in the glabrous skin are mainly innervated by only SAI mechanoreceptors. In addition, our results suggest that neonatal Ret+ Merkel cell innervating fibers most likely belong to the late but not early Ret+ DRG neurons. PMID:24637732

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

PubMed

Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Arterial innervation in development and disease.

PubMed

Eichmann, Anne; Brunet, Isabelle

2014-09-03

Innervation of arteries by sympathetic nerves is well known to control blood supply to organs. Recent studies have elucidated the mechanisms that regulate the development of arterial innervation and show that in addition to vascular tone, sympathetic nerves may also influence arterial maturation and growth. Understanding sympathetic arterial innervation may lead to new approaches to treat peripheral arterial disease and hypertension. Copyright © 2014, American Association for the Advancement of Science.

Morphological evidences in circumvallate papilla and von Ebners' gland development in mice

PubMed Central

Sohn, Wern-Joo; Gwon, Gi-Jeong; An, Chang-Hyeon; Moon, Cheil; Bae, Yong-Chul; Yamamoto, Hitoshi; Lee, Sanggyu

2011-01-01

In rodents, the circumvallate papilla (CVP), with its underlying minor salivary gland, the von Ebners' gland (VEG), is located on the dorsal surface of the posterior tongue. Detailed morphological processes to form the proper structure of CVP and VEG have not been properly elucidated. In particular, the specific localization patterns of taste buds in CVP and the branching formation of VEG have not yet been elucidated. To understand the developmental mechanisms underlying CVP and VEG formation, detailed histological observations of CVP and VEG were examined using a three-dimensional computer-aided reconstruction method with serial histological sections and pan-Cytokeratins immunostainings. In addition, to define the developmental processes in CVP and VEG formation, we examined nerve innervations and cell proliferation using microinjections of AM1-43 and immunostainings with various markers, including phosphoinositide 3-kinase, Ki-67, PGP9.5, and Ulex europaeus agglutinin 1 (UEA1). Results revealed specific morphogenesis of CVP and VEG with nerve innervations patterns, evaluated by the coincided localization patterns of AM1-43 and UEA1. Based on these morphological and immunohistochemical results, we suggest that nerve innervations and cell proliferations play important roles in the positioning of taste buds in CVP and branching morphogenesis of VEG in tongue development. PMID:22254156

The non-human primate striatum undergoes marked prolonged remodeling during postnatal development

PubMed Central

Martin, Lee J.; Cork, Linda C.

2014-01-01

We examined the postnatal ontogeny of the striatum in rhesus monkeys (Macaca mulatta) to identify temporal and spatial patterns of histological and chemical maturation. Our goal was to determine whether this forebrain structure is developmentally static or dynamic in postnatal life. Brains from monkeys at 1 day, 1, 4, 6, 9, and 12 months of age (N = 12) and adult monkeys (N = 4) were analyzed. Nissl staining was used to assess striatal volume, cytoarchitecture, and apoptosis. Immunohistochemistry was used to localize and measure substance P (SP), leucine-enkephalin (LENK), tyrosine hydroxylase (TH), and calbindin D28 (CAL) immunoreactivities. Mature brain to body weight ratio was achieved at 4 months of age, and striatal volume increased from ∼1.2 to ∼1.4 cm3 during the first postnatal year. Nissl staining identified, prominently in the caudate nucleus, developmentally persistent discrete cell islands with neuronal densities greater than the surrounding striatal parenchyma (matrix). Losses in neuronal density were observed in island and matrix regions during maturation, and differential developmental programmed cell death was observed in islands and matrix regions. Immunohistochemistry revealed striking changes occurring postnatally in striatal chemical neuroanatomy. At birth, the immature dopaminergic nigrostriatal innervation was characterized by islands enriched in TH-immunoreactive puncta (putative terminals) in the neuropil; TH-enriched islands aligned completely with areas enriched in SP immunoreactivity but low in LENK immunoreactivity. These areas enriched in SP immunoreactivity but low in LENK immunoreactivity were identified as striosome and matrix areas, respectively, because CAL immunoreactivity clearly delineated these territories. SP, LENK, and CAL immunoreactivities appeared as positive neuronal cell bodies, processes, and puncta. The matrix compartment at birth contained relatively low TH-immunoreactive processes and few SP-positive neurons but was densely populated with LENK-immunoreactive neurons. The nucleus accumbens part of the ventral striatum also showed prominent differences in SP, LENK, and CAL immunoreactivities in shell and core territories. During 12 months of postnatal maturation salient changes occurred in neurotransmitter marker localization: TH-positive afferents densely innervated the matrix to exceed levels of immunoreactivity in the striosomes; SP immunoreactivity levels increased in the matrix; and LENK-immunoreactivity levels decreased in the matrix and increased in the striosomes. At 12 months of age, striatal chemoarchitecture was similar qualitatively to adult patterns, but quantitatively different in LENK and SP in caudate, putamen, and nucleus accumbens. This study shows for the first time that the rhesus monkey striatum requires more than 12 months after birth to develop an adult-like pattern of chemical neuroanatomy and that principal neurons within striosomes and matrix have different developmental programs for neuropeptide expression. We conclude that postnatal maturation of the striatal mosaic in primates is not static but, rather, is a protracted and dynamic process that requires many synchronous and compartment-selective changes in afferent innervation and in the expression of genes that regulate neuronal phenotypes. PMID:25294985

Vasopressin Innervation of the Mouse (Mus musculus) Brain and Spinal Cord

PubMed Central

Rood, Benjamin D.; De Vries, Geert J.

2014-01-01

The neuropeptide vasopressin (AVP) has been implicated in the regulation of numerous physiological and behavioral processes. Although mice have become an important model for studying this regulation, there is no comprehensive description of AVP distribution in the mouse brain and spinal cord. With C57BL/6 mice, we used immunohistochemistry to corroborate the location of AVP-containing cells and to define the location of AVP-containing fibers throughout the mouse central nervous system. We describe AVP-immunoreactive (-ir) fibers in midbrain, hindbrain, and spinal cord areas, which have not previously been reported in mice, including innervation of the ventral tegmental area, dorsal and median raphe, lateral and medial parabrachial, solitary, ventrolateral periaqueductal gray, and interfascicular nuclei. We also provide a detailed description of AVP-ir innervation in heterogenous regions such as the amygdala, bed nucleus of the stria terminalis, and ventral forebrain. In general, our results suggest that, compared with other species, the mouse has a particularly robust and widespread distribution of AVP-ir fibers, which, as in other species, originates from a number of different cell groups in the telencephalon and diencephalon. Our data also highlight the robust nature of AVP innervation in specific regulatory nuclei, such as the ventral tegmental area and dorsal raphe nucleus among others, that are implicated in the regulation of many behaviors. PMID:21456024

Marked innervation but also signs of nerve degeneration in between the Achilles and plantaris tendons and presence of innervation within the plantaris tendon in midportion Achilles tendinopathy

PubMed Central

Spang, C.; Harandi, V.M.; Alfredson, H.; Forsgren, S.

2015-01-01

Objectives: The plantaris tendon is increasingly recognised as an important factor in midportion Achilles tendinopathy. Its innervation pattern is completely unknown. Methods: Plantaris tendons (n=56) and associated peritendinous tissue from 46 patients with midportion Achilles tendinopathy and where the plantaris tendon was closely related to the Achilles tendon were evaluated. Morphological evaluations and stainings for nerve markers [general (PGP9.5), sensory (CGRP), sympathetic (TH)], glutamate NMDA receptor and Schwann cells (S-100β) were made. Results: A marked innervation, as evidenced by evaluation for PGP9.5 reactions, occurred in the peritendinous tissue located between the plantaris and Achilles tendons. It contained sensory and to some extent sympathetic and NMDAR1-positive axons. There was also an innervation in the zones of connective tissue within the plantaris tendons. Interestingly, some of the nerve fascicles showed a partial lack of axonal reactions. Conclusion: New information on the innervation patterns for the plantaris tendon in situations with midportion Achilles tendinopathy has here been obtained. The peritendinous tissue was found to be markedly innervated and there was also innervation within the plantaris tendon. Furthermore, axonal degeneration is likely to occur. Both features should be further taken into account when considering the relationship between the nervous system and tendinopathy. PMID:26032213

Afferent innervation patterns of the saccule in pigeons

NASA Technical Reports Server (NTRS)

Zakir, M.; Huss, D.; Dickman, J. D.

2003-01-01

The innervation patterns of vestibular saccular afferents were quantitatively investigated in pigeons using biotinylated dextran amine as a neural tracer and three-dimensional computer reconstruction. Type I hair cells were found throughout a large portion of the macula, with the highest density observed in the striola. Type II hair cells were located throughout the macula, with the highest density in the extrastriola. Three classes of afferent innervation patterns were observed, including calyx, dimorph, and bouton units, with 137 afferents being anatomically reconstructed and used for quantitative comparisons. Calyx afferents were located primarily in the striola, innervated a number of type I hair cells, and had small innervation areas. Most calyx afferent terminal fields were oriented parallel to the anterior-posterior axis and the morphological polarization reversal line. Dimorph afferents were located throughout the macula, contained fewer type I hair cells in a calyceal terminal than calyx afferents and had medium sized innervation areas. Bouton afferents were restricted to the extrastriola, with multi-branching fibers and large innervation areas. Most of the dimorph and bouton afferents had innervation fields that were oriented dorso-ventrally but were parallel to the neighboring reversal line. The organizational morphology of the saccule was found to be distinctly different from that of the avian utricle or lagena otolith organs and appears to represent a receptor organ undergoing evolutionary adaptation toward sensing linear motion in terrestrial and aerial species.

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing

PubMed Central

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H. Sophie; Wahis, Jérôme; Gouveia, Miriam da Silva; Tang, Yan; Ciobanu, Alexandru Cristian; del Rio, Rodrigo Triana; Roth, Lena C.; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L.; Mitre, Mariela; Froemke, Robert C.; Chao, Moses V.; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H.; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2017-01-01

SUMMARY Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. PMID:26948889

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

PubMed

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2016-03-16

Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

Nervous control of fish swimbladders.

PubMed

Nilsson, Stefan

2009-01-01

The swimbladder of teleost fish receives a rich and complex innervation by nerve fibres of the autonomic nervous system. While an understanding of the form and function of a non-adrenergic, non-cholinergic innervation is slowly emerging, the pattern of control by the "classical" cholinergic and adrenergic innervation is becoming relatively well understood. This short review describes the autonomic innervation patterns, and attempts to summarise the role of cholinergic and adrenergic pathways in the control of gas secretion and resorption in the teleost swimbladder.

Merkel-like cell distribution in the epithelium of the human vagina. An immunohistochemical and TEM study.

PubMed

Polakovičová, Simona; Csöbönyeiová, Mária; Filova, Barbora; Borovský, Miroslav; Maršík, Ladislav; Kvasilová, Alena; Polák, Štefan

2018-02-16

Human Merkel cells (MCs) were first described by Friedrich S. Merkel in 1875 and named "Tastzellen" (touch cells). Merkel cells are primarily localized in the basal layer of the epidermis and concentrated in touch-sensitive areas. In our previous work, we reported on the distribution of MCs in the human esophagus, so therefore we chose other parts of the human body to study them. We selected the human vagina, because it has a similar epithelium as the esophagus and plays very important roles in reproduction and sexual pleasure. Due to the fact that there are very few research studies focusing on the innervation of this region, we decided to investigate the occurrence of MCs in the anterior wall of the vagina. The aim of our research was to identify MCs in the stratified squamous non-keratinized epithelium of the human vagina in 20 patients. For the identification of Merkel cells by light microscopy, we used antibodies against simple-epithelial cytokeratins (especially anti-cytokeratin 20). We also tried to identify them using transmission electron microscopy. Our investigation confirmed that 10 (50 %) of 20 patients had increased number of predominantly intraepithelial CK20 positive "Merkel-like" cells (MLCs) in the human vaginal epithelium. Subepithelial CK20 positive MLCs were observed in only one patient (5%). We tried to identify them also using transmission electron microscopy. Our investigation detected some unique cells that may be MCs. The purpose of vaginal innervation is still unclear. There are no data available concerning the distribution of MCs in the human vagina, so it would be interesting to study the role of MCs in the vaginal epithelium, in the context of innervation and epithelial biology.

Lingual and Palatal Gustatory Afferents Each Depend on Both BDNF and NT-4, but the Dependence Is Greater for Lingual than Palatal Afferents

PubMed Central

Patel, Ami V.; Huang, Tao; Krimm, Robin F.

2012-01-01

Neurons of the geniculate ganglion innervate taste buds located in two spatially distinct targets, the tongue and palate. About 50% of these neurons die in Bdnf−/− mice and Ntf4/5−/− mice. Bdnf−/−/Ntf4/5−/− double mutants lose 90-95% of geniculate ganglion neurons. To determine whether different subpopulations are differentially influenced by neurotrophins, we quantified neurons from two ganglion subpopulations separately and remaining taste buds at birth within each target field in wild-type, Bdnf−/−, Ntf4/5−/−, and Bdnf−/−/Ntf4/5−/− mice. In wild-type mice the same number of neurons innervated the anterior tongue and soft palate and each target contained the same number of taste buds. Compared to wild-type mice, Bdnf−/− mice showed a 50% reduction in geniculate neurons innervating the tongue and a 28% loss in neurons innervating the soft palate. Ntf4/5−/− mice lost 58% of the neurons innervating the tongue and 41% of the neurons innervating the soft palate. Taste bud loss was not as profound in the NT-4 null mice compared to BDNF-null mice. Tongues of Bdnf−/−/Ntf4/5−/− mice were innervated by 0 to 4 gustatory neurons and contained 3 to 16 taste buds at birth, indicating that some taste buds remain even when all innervation is lost. Thus, gustatory neurons are equally dependent on BDNF and NT-4 expression for survival, regardless of what peripheral target they innervate. However, taste buds are more sensitive to BDNF than NT-4 removal. PMID:20575060

The central projections of the laryngeal nerves in the rat

PubMed Central

Pascual-Font, Arán; Hernández-Morato, Ignacio; McHanwell, Stephen; Vázquez, Teresa; Maranillo, Eva; Sañudo, Jose; Valderrama-Canales, Francisco J

2011-01-01

The larynx serves respiratory, protective, and phonatory functions. The motor and sensory innervation to the larynx controlling these functions is provided by the superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN). Classical studies state that the SLN innervates the cricothyroid muscle and provides sensory innervation to the supraglottic cavity, whereas the RLN supplies motor innervation to the remaining intrinsic laryngeal muscles and sensory innervation to the infraglottic cavity, but recent data suggest a more complex anatomical and functional organisation. The current neuroanatomical tracing study was undertaken to provide a comprehensive description of the central brainstem connections of the axons within the SLN and the RLN, including those neurons that innervate the larynx. The study has been carried out in 41 adult male Sprague–Dawley rats. The central projections of the laryngeal nerves were labelled following application of biotinylated dextran amines onto the SLN, the RLN or both. The most remarkable result of the study is that in the rat the RLN does not contain any afferent axons from the larynx, in contrast to the pattern observed in many other species including man. The RLN supplied only special visceromotor innervation to the intrinsic muscles of the larynx from motoneurons in the nucleus ambiguus (Amb). All the afferent axons innervating the larynx are contained within the SLN, and reach the nucleus of the solitary tract. The SLN also contained secretomotor efferents originating from motoneurons in the dorsal motor nucleus of the vagus, and special visceral efferent fibres from the Amb. In conclusion, the present study shows that in the rat the innervation of the larynx differs in significant ways from that described in other species. PMID:21599662

Spatial distribution of neurons innervated by chandelier cells.

PubMed

Blazquez-Llorca, Lidia; Woodruff, Alan; Inan, Melis; Anderson, Stewart A; Yuste, Rafael; DeFelipe, Javier; Merchan-Perez, Angel

2015-09-01

Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells and are thus thought to have an important role in controlling the activity of cortical circuits. To examine the circuit connectivity of chandelier cells (ChCs), we made use of a genetic targeting strategy to label neocortical ChCs in upper layers of juvenile mouse neocortex. We filled individual ChCs with biocytin in living brain slices and reconstructed their axonal arbors from serial semi-thin sections. We also reconstructed the cell somata of pyramidal neurons that were located inside the ChC axonal trees and determined the percentage of pyramidal neurons whose axon initial segments were innervated by ChC terminals. We found that the total percentage of pyramidal neurons that were innervated by a single labeled ChC was 18-22 %. Sholl analysis showed that this percentage peaked at 22-35 % for distances between 30 and 60 µm from the ChC soma, decreasing to lower percentages with increasing distances. We also studied the three-dimensional spatial distribution of the innervated neurons inside the ChC axonal arbor using spatial statistical analysis tools. We found that innervated pyramidal neurons are not distributed at random, but show a clustered distribution, with pockets where almost all cells are innervated and other regions within the ChC axonal tree that receive little or no innervation. Thus, individual ChCs may exert a strong, widespread influence on their local pyramidal neighbors in a spatially heterogeneous fashion.

Functional asymmetry of pelvic floor innervation and its role in the pathogenesis of fecal incontinence.

PubMed

Enck, Paul; Hinninghofen, Heidemarie; Wietek, Beate; Becker, Horst D

2004-01-01

While the regular and symmetric innervation of the pelvic floor has been regarded as "established" for many years, recent data indicate that asymmetry of innervation of the sphincters may exists and may contribute to the occurrence and severity of incontinence symptoms in case of pelvic floor trauma. A systematic review of published papers on asymmetry of sphincter innervation was performed including studies in healthy volunteers and patients with incontinence. 234 consecutive patients with fecal incontinence were investigated by means of side-separated mass surface EMG from the left and right side anal canal, these data were correlated to clinical and anamnestic findings. The literature survey indicates that asymmetry of sphincter innervation exists in a subgroup of healthy male and female volunteers, and may be a risk factor to become incontinent in case of trauma. Patients with incontinence in whom asymmetry of sphincter innervation could be shown more frequently reported a history of pelvic floor trauma during childbirth. Childbirth per se but not the number of deliveries predicted sphincter asymmetry. Asymmetrically innervated sphincters show a compromised sphincter function in routine anorectal manometry. Assessment of sphincter innervation asymmetry may be of value in clinical routine testing of patients with incontinence. However, a new technology is needed to replace mass surface EMG by multi-electrode arrays on a sphincter probe. This is one of the goals of the EU-sponsored research project OASIS. Copyright 2004 S. Karger AG, Basel

Vagal Afferent Innervation of the Lower Esophageal Sphincter

PubMed Central

Powley, Terry L.; Baronowsky, Elizabeth A.; Gilbert, Jared M.; Hudson, Cherie N.; Martin, Felecia N.; Mason, Jacqueline K.; McAdams, Jennifer L.; Phillips, Robert J.

2013-01-01

To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions. PMID:23583280

Innervation of the Anterior Sacroiliac Joint.

PubMed

Cox, Marcus; Ng, Garrett; Mashriqi, Faizullah; Iwanaga, Joe; Alonso, Fernando; Tubbs, Kevin; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

2017-11-01

Sacroiliac joint pain can be disabling and recalcitrant to medical therapy. The innervation of this joint is poorly understood, especially its anterior aspect. Therefore, the present cadaveric study was performed to better elucidate this anatomy. Twenty-four cadaveric sides underwent dissection of the anterior sacroiliac joint, with special attention given to any branches from regional nerves to this joint. No femoral, obturator, or lumbosacral trunk branches destined to the anterior sacroiliac joint were identified in the 24 sides. In 20 sides, one or two small branches (less than 0.5 mm in diameter) were found to arise from the L4 ventral ramus (10%), the L5 ventral ramus (80%), or simultaneously from both the L4 and L5 ventral rami (10%). The length of the branches ranged from 5 to 31 mm (mean, 14 mm). All these branches arose from the posterior part of the nerves and traveled to the anterior surface of the sacroiliac joint. No statistical significance was found between sides or sexes. An improved knowledge of the innervation of the anterior sacroiliac joint might decrease suffering in patients with chronic sacroiliac joint pain. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolution of the vestibulo-ocular system

NASA Technical Reports Server (NTRS)

Fritzsch, B.

1998-01-01

The evolutionary and developmental changes in the eye muscle innervation, the inner ear, and the vestibulo-ocular reflex are examined. Three eye muscle patterns, based on the innervation by distinct ocular motoneurons populations, can be identified: a lamprey, an elasmobranch, and a bony fish/tetrapod pattern. Four distinct patterns of variation in the vestibular system are described: a hagfish pattern, a lamprey pattern, an elasmobranch pattern, and a bony fish/tetrapod pattern. Developmental data suggest an influence of the hindbrain on ear pattern formation, thus potentially allowing a concomitant change of eye muscle innervation and ear variation. The connections between the ear and the vestibular nuclei and between the vestibular nuclei and ocular motoneurons are reviewed, and the role of neurotrophins for pattern specification is discussed. Three patterns are recognized in central projections: a hagfish pattern, a lamprey pattern, and a pattern for jawed vertebrates. Second-order connections show both similarities and differences between distantly related species such as lampreys and mammals. For example, elasmobranchs lack an internuclear system, which is at best poorly developed in lampreys. It is suggested that the vestibulo-ocular system shows only a limited degree of variation because of the pronounced functional constraints imposed on it.

FMRFamide-like immunoreactive nervus terminalis innervation to the pituitary in the catfish, Clarias batrachus (Linn.): demonstration by lesion and immunocytochemical techniques

NASA Technical Reports Server (NTRS)

Krishna, N. S.; Subhedar, N.; Schreibman, M. P.

1992-01-01

Certain thick FMRFamide-like immunoreactive fibers arising from the ganglion cells of nervus terminalis in the olfactory bulb of Clarias batrachus can be traced centripetally through the medial olfactory tract, telencephalon, lateral preoptic area, tuberal area, and hypothalamohypophysial tract to the pituitary. Following 6 days of bilateral olfactory tract transection, the immunoreactivity in the thick fibers, caudal to the lesion site, was partially eliminated, whereas after 10 and 14 days, it was totally abolished in the processes en route to the pituitary. The results indicate a direct innervation of the pituitary gland by the FMRFamide-like peptide containing fibers of the nervus terminalis.

Effect of an inhibitor of noradrenaline uptake, desipramine, on cell proliferation in the intestinal crypt epithelium.

PubMed

Tutton, P J; Barkla, D H

1989-01-01

The intestinal mucosa receives an adrenergic innervation for which there is no commonly accepted function. However, in recent years, cell kinetic studies have raised the possibility that this innervation may be an important regulator of crypt cell proliferation. The effects of noradrenaline released from adrenergic nerves is terminated principally by re-uptake of the amine into the nerve and this process can be inhibited by the antidepressant drug, desipramine. In this report desipramine is shown to accelerate crypt cell proliferation in intact, but not in chemically sympathectomized rats, thus adding support to the notion that regulation of crypt cell division is an important function of the sympathetic nervous system.

Independent and Collaborative Contributions of the Cerebral Hemispheres to Emotional Processing

PubMed Central

Shobe, Elizabeth R.

2014-01-01

Presented is a model suggesting that the right hemisphere (RH) directly mediates the identification and comprehension of positive and negative emotional stimuli, whereas the left hemisphere (LH) contributes to higher level processing of emotional information that has been shared via the corpus callosum. RH subcortical connections provide initial processing of emotional stimuli, and their innervation to cortical structures provides a secondary pathway by which the hemispheres process emotional information more fully. It is suggested that the LH contribution to emotion processing is in emotional regulation, social well-being, and adaptation, and transforming the RH emotional experience into propositional and verbal codes. Lastly, it is proposed that the LH has little ability at the level of emotion identification, having a default positive bias and no ability to identify a stimulus as negative. Instead, the LH must rely on the transfer of emotional information from the RH to engage higher-order emotional processing. As such, either hemisphere can identify positive emotions, but they must collaborate for complete processing of negative emotions. Evidence presented draws from behavioral, neurological, and clinical research, including discussions of subcortical and cortical pathways, callosal agenesis, commissurotomy, emotion regulation, mood disorders, interpersonal interaction, language, and handedness. Directions for future research are offered. PMID:24795597

Cranial nerves in the Australian lungfish, Neoceratodus forsteri, and in fossil relatives (Osteichthyes: Dipnoi).

PubMed

Kemp, A

2017-02-01

Three systems, two sensory and one protective, are present in the skin of the living Australian lungfish, Neoceratodus forsteri, and in fossil lungfish, and the arrangement and innervation of the sense organs is peculiar to lungfish. Peripheral branches of nerves that innervate the sense organs are slender and unprotected, and form before any skeletal structures appear. When the olfactory capsule develops, it traps some of the anterior branches of cranial nerve V, which emerged from the chondrocranium from the lateral sphenotic foramen. Cranial nerve I innervates the olfactory organ enclosed within the olfactory capsule and cranial nerve II innervates the eye. Cranial nerve V innervates the sense organs of the snout and upper lip, and, in conjunction with nerve IX and X, the sense organs of the posterior and lateral head. Cranial nerve VII is primarily a motor nerve, and a single branch innervates sense organs in the mandible. There are no connections between nerves V and VII, although both emerge from the brain close to each other. The third associated system consists of lymphatic vessels covered by an extracellular matrix of collagen, mineralised as tubules in fossils. Innervation of the sensory organs is separate from the lymphatic system and from the tubule system of fossil lungfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nociceptive and Inflammatory Mediator Upregulation in a Mouse Model of Chronic Prostatitis

PubMed Central

Schwartz, Erica S.; Xie, Amy; La, Jun-Ho; Gebhart, G.F.

2015-01-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis. PMID:25915147

Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

PubMed

Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

2015-08-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

Innervation of the wrist joint and surgical perspectives of denervation.

PubMed

Van de Pol, Gerrit J; Koudstaal, Maarten J; Schuurman, Arnold H; Bleys, Ronald L A W

2006-01-01

Because our experience with the techniques used in denervation surgery of the wrist joint often has proven insufficient in treating chronic pain we conducted an anatomic study to clarify the exact contributions of the nerves supplying the wrist joint. Our goal was to reveal all periosteal and capsular nerve connections and if necessary adjust our technique used in denervation surgery. Innervation of the wrist joint was investigated by microdissection and histologic examination of 18 human wrists. An acetylcholinesterase method was used to identify the nerves, both in whole-mount preparations and in sections. We found that the main innervation to the wrist capsule and periosteal nerve network came from the anterior interosseous nerve, lateral antebrachial cutaneous nerve, and posterior interosseous nerve. The palmar cutaneous branch of the median nerve, the deep branch of the ulnar nerve, the superficial branch of the radial nerve, and the dorsal branch of the ulnar nerve also were found to have connections with the capsule. The periosteal nerve branches did not appear to play a major role in the innervation of the capsule and ligaments; here the specific articular nerve branches proved more important. The posterior and medial antebrachial cutaneous nerves did not connect to the wrist capsule or periosteum but rather terminated in the extensor and flexor retinaculum. Based on our findings we propose to denervate the wrist by making 2 incisions. With one palmar and one dorsal incision it should be possible to disconnect the periosteum from the capsule and interrupt the majority of the capsular nerve branches.

Defective parasympathetic innervation is associated with airway branching abnormalities in experimental CDH

PubMed Central

Rhodes, Julie; Saxena, Deeksha; Zhang, GuangFeng; Gittes, George K.

2015-01-01

Developmental mechanisms leading to lung hypoplasia in congenital diaphragmatic hernia (CDH) remain poorly defined. Pulmonary innervation is defective in the human disease and in the rodent models of CDH. We hypothesize that defective parasympathetic innervation may contribute to airway branching abnormalities and, therefore, lung hypoplasia, during lung development in CDH. The murine nitrofen model of CDH was utilized to study the effect of the cholinergic agonist carbachol on embryonic day 11.5 (E11.5) lung explant cultures. Airway branching and contractions were quantified. In a subset of experiments, verapamil was added to inhibit airway contractions. Sox9 immunostaining and 5-bromo-2-deoxyuridine incorporation were used to identify and quantify the number and proliferation of distal airway epithelial progenitor cells. Intra-amniotic injections were used to determine the in vivo effect of carbachol. Airway branching and airway contractions were significantly decreased in nitrofen-treated lungs compared with controls. Carbachol resulted in increased airway contractions and branching in nitrofen-treated lungs. Nitrofen-treated lungs exhibited an increased number of proliferating Sox9-positive distal epithelial progenitor cells, which were decreased and normalized by treatment with carbachol. Verapamil inhibited the carbachol-induced airway contractions in nitrofen-treated lungs but had no effect on the carbachol-induced increase in airway branching, suggesting a direct carbachol effect independent of airway contractions. In vivo treatment of nitrofen-treated embryos via amniotic injection of carbachol at E10.5 resulted in modest increases in lung size and branching at E17.5. These results suggest that defective parasympathetic innervation may contribute to airway branching abnormalities in CDH. PMID:25934671

Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes

PubMed Central

Tian, Haibin; Lu, Yan; Laborde, James Monroe; Muhale, Filipe A.; Wang, Quansheng; Alapure, Bhagwat V.; Serhan, Charles N.; Bazan, Nicolas G.

2014-01-01

Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MΦs from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MΦs. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MΦs functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MΦs involved 1) attenuating MΦ inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MΦ production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MΦs-produced factor that accelerates diabetic wound healing and promotes MΦ pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MΦs for treatment of diabetic wounds. PMID:25273880

Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes.

PubMed

Hong, Song; Tian, Haibin; Lu, Yan; Laborde, James Monroe; Muhale, Filipe A; Wang, Quansheng; Alapure, Bhagwat V; Serhan, Charles N; Bazan, Nicolas G

2014-12-01

Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MΦs from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MΦs. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MΦs functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MΦs involved 1) attenuating MΦ inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MΦ production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MΦs-produced factor that accelerates diabetic wound healing and promotes MΦ pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MΦs for treatment of diabetic wounds. Copyright © 2014 the American Physiological Society.

[Adrenergic innervation of the kidneys in man and various laboratory animals].

PubMed

Shvalev, V N; Chzhao, L Kh

1988-07-01

By means of the neurohistochemical method for slice incubation in 2% solution of glyoxylic acid, innervation of the kidneys of a 57-year-old man after a sudden cardiac death has been investigated, as well as innervation of the kidneys in white rat, rabbit, guinea pig and cat. A rich adrenergic innervation in the organ's blood vessels has been revealed. In particular, adrenergic nervous fibers have been found along the course of afferent glomerular arterioles. Together with innervation of the proximal and distal convoluted tubules, a high density of the terminal adrenergic nervous plexus is revealed along the course of the nephron loops. Adrenergic nervous plexuses of high density are found in the area of the initial part of the urinary excretory pathways and their connection with nervous plexuses of the kidney itself.

Functional asymmetry of pelvic floor innervation--myth or fact?

PubMed

Enck, Paul

2004-01-01

Neurophysiology of the pelvic floor is not completely understood yet. The importance of its symmetry and asymmetry of innervation has been pointed out lately. These facts have the clinical relevance in case of pelvic floor trauma or incontinence surgery. New techniques of EMG are necessary to confirm correlations between symptoms development and asymmetry of sphincter innervation.

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

PubMed

Sakamoto, Junya; Manabe, Yoshitaka; Oyamada, Joichi; Kataoka, Hideki; Nakano, Jiro; Saiki, Kazunobu; Okamoto, Keishi; Tsurumoto, Toshiyuki; Okita, Minoru

2018-07-01

Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705-709, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Doublecortin is expressed in trigeminal motoneurons that innervate the velar musculature of lampreys: considerations on the evolution and development of the trigeminal system.

PubMed

Barreiro-Iglesias, Antón; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Rodicio, María Celina

2011-01-01

Studies in lampreys have revealed interesting aspects of the evolution of the trigeminal system and the jaw. In the present study, we found a marker that distinguishes subpopulations of trigeminal motoneurons innervating two different kinds of oropharyngeal muscles. Immunofluorescence with an antibody against doublecortin (DCX; a neuron-specific phosphoprotein) enabled identification of the trigeminal motoneurons that innervate the velar musculature of larval and recently transformed sea lampreys. DCX-immunoreactive (-ir) motoneurons were observed in the rostro-lateral part of the trigeminal motor nucleus of these animals, but not in lampreys 1 month or more after metamorphosis. Combined double DCX/tubulin and serotonin/tubulin immunofluorescence and tract-tracing experiments with neurobiotin (NB) were also performed in larvae for further characterization of this system. Rich innervation by DCX-ir fibers was observed on the muscle fibers of the velum but not on the upper lip or lower lip muscles, which were innervated by tubulin-ir/DCX-negative fibers. No double-labelled DCX-ir motoneurons were observed in experiments in which the tracer NB was applied to the upper lip. Innervation of velar muscles by serotonergic fibers is also reported. The present results indicate that development of the trigeminal motoneurons innervating the velum differs from that of the trigeminal motoneurons innervating the lips, which is probably related to the dramatic regression of the velum during metamorphosis. The absence of data on a similar subsystem in the trigeminal motor nucleus of gnathostomes suggests that they may be lamprey-specific motoneurons. These results provide support for the "heterotopic theory" of jaw evolution and are inconsistent with the theories of a velar origin for the gnathostome jaw. © 2011 Wiley Periodicals, Inc.

Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse

PubMed Central

Mukudai, Shigeyuki; Ichi Matsuda, Ken; Bando, Hideki; Takanami, Keiko; Nishio, Takeshi; Sugiyama, Yoichiro; Hisa, Yasuo; Kawata, Mitsuhiro

2016-01-01

The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor α (ERα), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERα were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERα. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus. PMID:27006520

Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons

NASA Technical Reports Server (NTRS)

Postigo, Antonio; Calella, Anna Maria; Fritzsch, Bernd; Knipper, Marlies; Katz, David; Eilers, Andreas; Schimmang, Thomas; Lewin, Gary R.; Klein, Rudiger; Minichiello, Liliana

2002-01-01

Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking the docking site for Shc adaptors (trkB(shc/shc) and trkC(shc/shc) mice), we show that TrkB and TrkC promote survival of sensory neurons mainly through Shc site-independent pathways, suggesting that these receptors use similar pathways to prevent apoptosis. In contrast, the regulation of target innervation appears different: in trkB(shc/shc) mice neurons lose target innervation, whereas in trkC(shc/shc) mice the surviving TrkC-dependent neurons maintain target innervation and function. Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC. Our findings show that although TrkB and TrkC signals mediating survival are largely similar, TrkB and TrkC signals required for maintenance of target innervation in vivo are regulated by distinct mechanisms.

[Physiology of the urethral sphincteric vesico-prostatic complex].

PubMed

Carmignani, L; Gadda, F; Dell'Orto, P; Ferruti, M; Grisotto, M; Rocco, F

2001-09-01

We propose a review of the literature about innervation and physiology of the urethral sphincteric complex. Parasympathetic innervation of the pelvic viscera comes from ventral branches of the sacral nerves (S2-S4). The orthosympathetic component derives from superior hypogastric plexus and runs down the hypogastric nerves to form the right and left pelvic plexus together with the parasympathetic component. The pelvic plexus is situated inferolaterally with respect to the rectum and runs on the surface of the levator ani muscle down to the prostatic apex. The pelvic plexus gives innervation to the rectum, the bladder, the prostate and the urethral sphincteric complex. The pelvic muscular floor is innervated by the somatic component (pudendal nerve) derived from the sacral branches (S2-S4). Bladder neck and smooth muscle urethral sphincter innervation is given mostly by the orthosympathetic component. The rhabdosphincter innervation comes from the pudendal nerve and from the pelvic plexus; its role in the continence mechanism is probably to give steady tonic urethral compression. Levator ani muscle takes part in the sphincteric complex with its anteromedial pubococcygeal portion. It plays its role strengthening the sphincteric tone during increase of the abdominal pressure or during active quick stop cessation of the urinary stream.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog.

PubMed

Waber-Wenger, Barbara; Forterre, Franck; Kuehni-Boghenbor, Kathrin; Danuser, Renzo; Stein, Jens Volker; Stoffel, Michael Hubert

2014-10-01

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

The anatomy of the hip abductor muscles.

PubMed

Flack, N A M S; Nicholson, H D; Woodley, S J

2014-03-01

The anatomy of the hip abductors has not been comprehensively examined, yet is important to understanding function and pathology in the gluteal region. For example, pathology of the hip abductor muscle-tendon complexes can cause greater trochanteric pain syndrome, and may be associated with gluteal atrophy and fatty infiltration. The purpose of this study was to investigate the detailed morphology of gluteus medius (GMed), gluteus minimus (GMin), and tensor fascia lata (TFL), and determine whether the muscles comprised anatomical compartments. The gluteal region from 12 cadavers was dissected and data collected on attachment sites, volume, fascicular and tendinous anatomy, and innervation. Three sites of GMed origin were identified (gluteal fossa, gluteal aponeurosis, and posteroinferior edge of the iliac crest) and the distal tendon had lateral and posterior parts. GMed was the largest in volume (27.6 ± 11.6 cm(3); GMin 14.1 ± 11.1 cm(3); TFL 1.8 ± 0.8 cm(3)). Fascicles of GMin originated from the gluteal fossa, inserting onto the deep surface of its distal tendon and the hip joint capsule. TFL was encapsulated in the fascia lata, having no bony attachment. Primary innervation patterns varied for GMed, with three or four branches supplying different regions of muscle. Distinct secondary nerve branches entered four regions of GMin; no differential innervation was observed for TFL. On the basis of architectural parameters and innervation, GMed, and GMin each comprise of four compartments but TFL is a homogenous muscle. It is anticipated that these data will be useful for future clinical and functional studies of the hip abductors. Copyright © 2013 Wiley Periodicals, Inc.

Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature

PubMed Central

Petruska, Jeffrey C.; Cooper, Brian Y.; Johnson, Richard D.

2014-01-01

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. PMID:24872531

High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake.

PubMed

Byerly, Mardi S; Fox, Edward A

2006-06-12

Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.

Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

PubMed

Rau, Kristofer K; Petruska, Jeffrey C; Cooper, Brian Y; Johnson, Richard D

2014-09-15

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. Copyright © 2014 the American Physiological Society.

Identification of neural circuits involved in female genital responses in the rat: A dual virus and anterograde tracing study

PubMed Central

Marson, L.; Murphy, A Z

2010-01-01

The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. In order to delineate forebrain input onto PRV labeled cells, the anterograde tracer biotinylated dextran amine (BDA) was injected into the medial preoptic nucleus (MPO), ventromedial nucleus of the hypothalamus (VMN) or the midbrain periaqueductal gray (PAG) 10 days prior to viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. Four days after viral injections, into the vagina and clitoris PRV labeled cells were observed in the paraventricular nucleus, Barrington’s nucleus, the A5 region, and the nucleus paragigantocellularis. At 5 days post-viral administration, additional PRV labeled cells were observed within the preoptic region, VMN, PAG and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV positive cells primarily within the dorsal paraventricular nucleus of the hypothalamus (PVN), ventrolateral VMN (VMNvl), caudal PAG and nucleus paragigantocellularis (nPGi). Anterograde labeling from the VMN terminated among PRV positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV positive cells in the PVN, ventral hypothalamus and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington's nucleus and ventromedial medulla received innervation from all three sources. These studies, together, identify several CNS sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses. PMID:16914428

Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

PubMed Central

Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.

2013-01-01

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032

Nerve supply of the subscapularis during anterior shoulder surgery: definition of a potential risk area.

PubMed

Leschinger, Tim; Hackl, Michael; Zeifang, Felix; Scaal, Martin; Müller, Lars Peter; Wegmann, Kilian

2017-01-01

The purpose of the study was to evaluate the position of the subscapular nerves relative to surgical landmarks during exposure and to analyze the pattern of innervation of the subscapularis to avoid injury during anterior shoulder surgery. 20 embalmed human cadaveric shoulder specimens were used in the study. The muscular insertions of the subscapular nerves were marked and their closest branches to the musculotendinous junction and the coracoid process were measured in horizontal and vertical distances. In addition, the innervation pattern of each specimen was documented. 14/20 specimens showed an innervation of the subscapularis with an upper, middle and lower subscapular nerve branch. Even though the nerve branches were in average more than 2 cm medial to the musculotendinous junction, minimal distances of 1.1-1.3 cm were found. The mean vertical distance as measured from the medial base of the coracoid to the nerve innervation point into the muscle was 0.7 cm for the upper nerve branch, 2.2 cm for the middle nerve branch and 4.4 cm for the lower nerve branch. The subscapularis has a variable nerve supply, which increases the risk of muscle denervation during open shoulder surgery. Dissection or release should be avoided at the anterior aspect of the subscapularis muscle more than 1 cm medial to the musculotendinous junction. In approaches with a horizontal incision of the subscapularis, splitting should be performed at a vertical distance of 3.2-3.6 cm to the coracoid base to avoid iatrogenic subscapular nerve injuries.

Expression of Vesicular Glutamate Transporters Type 1 and 2 in Sensory and Autonomic Neurons Innervating the Mouse Colorectum

PubMed Central

Brumovsky, Pablo R.; Robinson, David R.; La, Jun-Ho; Seroogy, Kim B.; Lundgren, Kerstin H.; Albers, Kathryn M.; Kiyatkin, Michael E.; Seal, Rebecca P.; Edwards, Robert H.; Watanabe, Masahiko; Hökfelt, Tomas; Gebhart, G.F.

2013-01-01

Vesicular glutamate transporters (VGLUTs) have been extensively studied in various neuronal systems, but their expression in visceral sensory and autonomic neurons remains to be analyzed in detail. Here we studied VGLUTs type 1 and 2 (VGLUT1 and VGLUT2, respectively) in neurons innervating the mouse colorectum. Lumbosacral and thoracolumbar dorsal root ganglion (DRG), lumbar sympathetic chain (LSC), and major pelvic ganglion (MPG) neurons innervating the colorectum of BALB/C mice were retrogradely traced with Fast Blue, dissected, and processed for immunohistochemistry. Tissue from additional naïve mice was included. Previously characterized antibodies against VGLUT1, VGLUT2, and calcitonin gene-related peptide (CGRP) were used. Riboprobe in situ hybridization, using probes against VGLUT1 and VGLUT2, was also performed. Most colorectal DRG neurons expressed VGLUT2 and often colocalized with CGRP. A smaller percentage of neurons expressed VGLUT1. VGLUT2-immunoreactive (IR) neurons in the MPG were rare. Abundant VGLUT2-IR nerves were detected in all layers of the colorectum; VGLUT1-IR nerves were sparse. A subpopulation of myenteric plexus neurons expressed VGLUT2 protein and mRNA, but VGLUT1 mRNA was undetectable. In conclusion, we show 1) that most colorectal DRG neurons express VGLUT2, and to a lesser extent, VGLUT1; 2) abundance of VGLUT2-IR fibers innervating colorectum; and 3) a subpopulation of myenteric plexus neurons expressing VGLUT2. Altogether, our data suggests a role for VGLUT2 in colorectal glutamatergic neurotransmission, potentially influencing colorectal sensitivity and motility. PMID:21800314

Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons

PubMed Central

Llewellyn-Smith, I.J.; Marina, N.; Manton, R.N.; Reimann, F.; Gribble, F.M.; Trapp, S.

2015-01-01

Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons. PMID:25450967

Early dietary sodium restriction disrupts the peripheral anatomical development of the gustatory system.

PubMed

Krimm, R F; Hill, D L

1999-05-01

Dietary sodium restriction has profound effects on the development of peripheral taste function and central taste system anatomy. This study examined whether early dietary sodium restriction also affects innervation of taste buds. The number of geniculate ganglion cells that innervate single fungiform taste buds were quantified for the midregion of the tongue in two groups of rats: those fed either a low-sodium diet and those fed a sodium replete diet (control rats) from early prenatal development through adulthood. The same mean number of ganglion cells in developmentally sodium-restricted and control adult rats innervated taste buds on the midregion of the tongue. However, the characteristic relationship of the larger the taste bud, the more neurons that innervate it did not develop in sodium-restricted rats. The failure to form such a relationship in experimental rats was likely due to a substantially smaller mean taste bud volume than controls and probably not to changes in innervation. Further experiments demonstrated that the altered association between number of innervating neurons and taste bud size in restricted rats was reversible. Feeding developmentally sodium-restricted rats a sodium replete diet at adulthood resulted in an increase in taste bud size. Accordingly, the high correlation between taste bud volume and innervation was established in sodium-replete rats. Findings from the current study reveal that early dietary manipulations influence neuron-target interactions; however, the effects of dietary sodium restriction on peripheral gustatory anatomy can be completely restored, even in adult animals.

Activation of oral trigeminal neurons by fatty acids is dependent upon intracellular calcium.

PubMed

Yu, Tian; Shah, Bhavik P; Hansen, Dane R; Park-York, MieJung; Gilbertson, Timothy A

2012-08-01

The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that conveys the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to stimulate rat trigeminal neurons has remained unexplored. Here, we found that several free fatty acids are capable of activating trigeminal neurons with different kinetics. Further, a polyunsaturated fatty acid, linoleic acid (LA), activates trigeminal neurons by increasing intracellular calcium concentration and generating depolarizing receptor potentials. Ion substitution and pharmacological approaches reveal that intracellular calcium store depletion is crucial for LA-induced signaling in a subset of trigeminal neurons. Using pseudorabies virus (PrV) as a live cell tracer, we identified a subset of lingual nerve-innervated trigeminal neurons that respond to different subsets of fatty acids. Quantitative real-time PCR of several transient receptor potential channel markers in individual neurons validated that PrV labeled a subset but not the entire population of lingual-innervated trigeminal neurons. We further confirmed that the LA-induced intracellular calcium rise is exclusively coming from the release of calcium stores from the endoplasmic reticulum in this subset of lingual nerve-innervated trigeminal neurons.

Innervation of the sinu-atrial node and neighbouring regions in two human embryos.

PubMed Central

Orts Llorca, F; Domenech Mateu, J M; Puerta Fonolla, J

1979-01-01

In human embryos of 20 to 23 mm (36 to 40 days) it is possible to identify on the right side a nerve that we may call the sinusal, which originates by several roots from the nervus vagus dexter (Figs. 1A, B, D), descending through the right ventrolateral face of the primary trachea and right bronchus (Fig. 2, arrows). Beaded in appearance, it gives a fine anastomotic branch which, passing in front of the arteria pulmonalis dextra, passes to the left side (Figs. 2B, C, D; AN). At this level it gives the large branch for the nodus sinoatrialis which, penetrating through the wall of the superior vena cava, provides a rich innervation for the nodus sinoatrialis which is already in an advanced stage of differentiation (Fig. 3, 2; Cy, D, AN). Afterwards it gives fine branches which, following the atrial fold, are distributed throughout the posterior face of the atrium dextrum (Fig. 3). It increases in diameter and, passing through the angle formed by the right pulmonary veins with the atrium dextrum, reaches the intrapericardial portion of the inferior vena cava in the vicinity of its outlet from the atrium (Fig. 3, arrows). The whole innervation is parasympathetic at the stages studied. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:438095

Primary afferent neurons express functional delta opioid receptors in inflamed skin.

PubMed

Brederson, Jill-Desiree; Honda, Christopher N

2015-07-21

Peripherally-restricted opiate compounds attenuate hyperalgesia in experimental models of inflammatory pain, but have little discernable effect on nociceptive behavior in normal animals. This suggests that activation of opioid receptors on peripheral sensory axons contributes to decreased afferent activity after injury. Previously, we reported that direct application of morphine to cutaneous receptive fields decreased mechanical and heat-evoked responses in a population of C-fiber nociceptors in inflamed skin. Consistent with reported behavioral studies, direct application of morphine had no effect on fiber activity in control skin. The aim of the present study was to determine whether mechanical responsiveness of nociceptors innervating inflamed skin was attenuated by direct activation of delta opioid receptors (DORs) on peripheral terminals. An ex vivo preparation of rat plantar skin and tibial nerve was used to examine effects of a selective DOR agonist, deltorphin II, on responsiveness of single fibers innervating inflamed skin. Electrical recordings were made eighteen hours after injection of complete Freund's adjuvant into the hindpaw. Deltorphin II produced an inhibition of the mechanical responsiveness of single fibers innervating inflamed skin; an effect blocked by the DOR-selective antagonist, naltrindole. The population of units responsive to deltorphin II was identified as consisting of C fiber mechanical nociceptors. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of Oral Trigeminal Neurons by Fatty Acids is Dependent upon Intracellular Calcium

PubMed Central

Yu, Tian; Shah, Bhavik P.; Hansen, Dane R.; Park-York, MieJung; Gilbertson, Timothy A.

2012-01-01

The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that conveys the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to stimulate rat trigeminal neurons has remained unexplored. Here, we found that several free fatty acids are capable of activating trigeminal neurons with different kinetics. Further, a polyunsaturated fatty acid, linoleic acid (LA), activates trigeminal neurons by increasing intracellular calcium concentration and generating depolarizing receptor potentials. Ion substitution and pharmacological approaches reveal that intracellular calcium store depletion is crucial for LA-induced signaling in a subset of trigeminal neurons. Using pseudorabies virus (PrV) as a live cell tracer, we identified a subset of lingual nerve-innervated trigeminal neurons that respond to different subsets of fatty acids. Quantitative real-time PCR of several transient receptor potential (TRP) channel markers in individual neurons validated that PrV labeled a subset but not the entire population of lingual-innervated trigeminal neurons. We further confirmed that the LA-induced intracellular calcium rise is exclusively coming from the release of calcium stores from the endoplasmic reticulum in this subset of lingual nerve-innervated trigeminal neurons. PMID:22644615

Central control of glucose homeostasis: the brain--endocrine pancreas axis.

PubMed

Thorens, B

2010-10-01

A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Intralaryngeal neuroanatomy of the recurrent laryngeal nerve of the rabbit

PubMed Central

Ryan, Stephen; McNicholas, Walter T; O'Regan, Ronan G; Nolan, Philip

2003-01-01

We undertook this study to determine the detailed neuroanatomy of the terminal branches of the recurrent laryngeal nerve (RLN) in the rabbit to facilitate future neurophysiological recordings from identified branches of this nerve. The whole larynx was isolated post mortem in 17 adult New Zealand White rabbits and prepared using a modified Sihler's technique, which stains axons and renders other tissues transparent so that nerve branches can be seen in whole mount preparations. Of the 34 hemi-laryngeal preparations processed, 28 stained well and these were dissected and used to characterize the neuroanatomy of the RLN. In most cases (23/28) the posterior cricoarytenoid muscle (PCA) was supplied by a single branch arising from the RLN, though in five PCA specimens there were two or three separate branches to the PCA. The interarytenoid muscle (IA) was supplied by two parallel filaments arising from the main trunk of the RLN rostral to the branch(es) to the PCA. The lateral cricoarytenoid muscle (LCA) commonly received innervation from two fine twigs branching from the RLN main trunk and travelling laterally towards the LCA. The remaining fibres of the RLN innervated the thyroarytenoid muscle (TA) and comprised two distinct branches, one supplying the pars vocalis and the other branching extensively to supply the remainder of the TA. No communicating anastomosis between the RLN and superior laryngeal nerve within the larynx was found. Our results suggest it is feasible to make electrophysiological recordings from identified terminal branches of the RLN supplying laryngeal adductor muscles separate from the branch or branches to the PCA. However, the very small size of the motor nerves to the IA and LCA suggests that it would be very difficult to record selectively from the nerve supply to individual laryngeal adductor muscles. PMID:12739619

Three-Dimensional Innervation Zone Imaging from Multi-Channel Surface EMG Recordings.

PubMed

Liu, Yang; Ning, Yong; Li, Sheng; Zhou, Ping; Rymer, William Z; Zhang, Yingchun

2015-09-01

There is an unmet need to accurately identify the locations of innervation zones (IZs) of spastic muscles, so as to guide botulinum toxin (BTX) injections for the best clinical outcome. A novel 3D IZ imaging (3DIZI) approach was developed by combining the bioelectrical source imaging and surface electromyogram (EMG) decomposition methods to image the 3D distribution of IZs in the target muscles. Surface IZ locations of motor units (MUs), identified from the bipolar map of their MU action potentials (MUAPs) were employed as a prior knowledge in the 3DIZI approach to improve its imaging accuracy. The performance of the 3DIZI approach was first optimized and evaluated via a series of designed computer simulations, and then validated with the intramuscular EMG data, together with simultaneously recorded 128-channel surface EMG data from the biceps of two subjects. Both simulation and experimental validation results demonstrate the high performance of the 3DIZI approach in accurately reconstructing the distributions of IZs and the dynamic propagation of internal muscle activities in the biceps from high-density surface EMG recordings.

THREE-DIMENSIONAL INNERVATION ZONE IMAGING FROM MULTI-CHANNEL SURFACE EMG RECORDINGS

PubMed Central

LIU, YANG; NING, YONG; LI, SHENG; ZHOU, PING; RYMER, WILLIAM Z.; ZHANG, YINGCHUN

2017-01-01

There is an unmet need to accurately identify the locations of innervation zones (IZs) of spastic muscles, so as to guide botulinum toxin (BTX) injections for the best clinical outcome. A novel 3-dimensional IZ imaging (3DIZI) approach was developed by combining the bioelectrical source imaging and surface electromyogram (EMG) decomposition methods to image the 3D distribution of IZs in the target muscles. Surface IZ locations of motor units (MUs), identified from the bipolar map of their motor unit action potentials (MUAPs) were employed as a prior knowledge in the 3DIZI approach to improve its imaging accuracy. The performance of the 3DIZI approach was first optimized and evaluated via a series of designed computer simulations, and then validated with the intramuscular EMG data, together with simultaneously recorded 128-channel surface EMG data from the biceps of two subjects. Both simulation and experimental validation results demonstrate the high performance of the 3DIZI approach in accurately reconstructing the distributions of IZs and the dynamic propagation of internal muscle activities in the biceps from high-density surface EMG recordings. PMID:26160432

Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors.

PubMed

Maor-Nof, Maya; Romi, Erez; Sar Shalom, Hadas; Ulisse, Valeria; Raanan, Calanit; Nof, Aviv; Leshkowitz, Dena; Lang, Roland; Yaron, Avraham

2016-12-07

Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription factor p53 and antagonizes the expression of the pro-degenerative factor, Puma (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16 protected axons from rapid degeneration and specifically reversed axonal innervation loss early in development with no effect on neuronal deficits. Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for crustacean cardioactive peptide-like innervation of the gut in Locusta migratoria.

PubMed

Donini, Andrew; Ngo, Caroline; Lange, Angela B

2002-11-01

Hindguts from female Vth instar larvae, young adults (1-2 days) and old adults (>10 days) are equally sensitive to the crustacean cardioactive peptide (CCAP), with changes in contraction occurring at a threshold concentration of 10(-9)M and maximal responses observed at concentrations ranging between 10(-7) and 5x10(-6)M. An immunohistochemical examination of the gut of Locusta migratoria with an antiserum raised against CCAP revealed an extensive network of CCAP-like immunoreactive processes on the hindgut and posterior midgut via the 11th sternal nerve arising from the terminal abdominal ganglion. Anterograde filling of the 11th sternal nerve with neurobiotin revealed extensive processes and terminals on the hindgut. Retrograde filling of the branch of the 11th sternal nerve which innervates the hindgut with neurobiotin revealed two bilaterally paired cells in the terminal abdominal ganglion which co-localized with CCAP-like immunoreactivity. Results suggest that a CCAP-like substance acts as a neurotransmitter/neuromodulator at the locust hindgut.

Neural control of renal tubular solute and water transport.

PubMed

DiBona, G F

1989-01-01

The neural control of renal tubular solute and water transport is recognized as an important physiological mechanism in the overall regulation of solute and water homeostasis by the mammalian organism. Recent studies have expanded the understanding of this mechanism concerning the transport of diverse solutes with beginning insight into the precise nature of the cellular transport processes involved. The modulatory roles of both circulating and intrarenal hormonal systems on the responses to alterations in the magnitude of efferent renal sympathetic nerve activity are being understood from the nerve terminal release of neurotransmitter to influences on cellular transport processes which determine the overall effect. When dietary sodium intake is normal or only modestly reduced, intact renal innervation is not essential for normal renal sodium conservation. However, when dietary sodium intake is severely restricted, there is maximum engagement of all mechanisms known to participate in renal sodium conservation and, under these conditions, intact renal innervation is essential for normal renal sodium conservation.

The innervation of the scalp: A comprehensive review including anatomy, pathology, and neurosurgical correlates

PubMed Central

Kemp, William J.; Tubbs, R. Shane; Cohen-Gadol, Aaron A.

2011-01-01

Background: Neurosurgical intervention involving the scalp may cause neuralgia or other pain syndromes. Therefore, a comprehensive understanding of scalp innervation may be helpful in prevention of pain potentially induced by surgery. Methods: Using standard search engines, a review of the literature regarding the anatomy of the nerves that innervate the scalp was performed with attention given to anatomic landmarks. Results: This paper provides a comprehensive review of the anatomy, embryology, pathology, and neurosurgical application of the knowledge of the innervation of the scalp. Conclusions: Knowledge of the nerves that supply the scalp is important to the neurosurgeon who hopes to maximize patient recovery and minimize post-procedural complications. PMID:22276233

AUTONOMIC AXONS IN THE HUMAN ENDOCRINE PANCREAS SHOW UNIQUE INNERVATION PATTERNS

PubMed Central

Rodriguez-Diaz, Rayner; Abdulreda, Midhat H.; Formoso, Alexander L.; Gans, Itai; Ricordi, Camillo; Berggren, Per-Olof; Caicedo, Alejandro

2011-01-01

SUMMARY The autonomic nervous system regulates hormone secretion from the endocrine pancreas, the islets of Langerhans, and thus impacts glucose metabolism. The parasympathetic and sympathetic nerves innervate the pancreatic islet, but the precise innervation patterns are not known, particularly in human islets. Here we demonstrate that the innervation of human islets is different from that of mouse islets and that it does not conform to existing models of autonomic control of islet function. By visualizing axons in three dimensions and quantifying axonal densities and contacts within pancreatic islets, we found that, in contrast to mouse endocrine cells, human endocrine cells are sparsely contacted by autonomic axons. Few parasympathetic cholinergic axons penetrate the human islet and the invading sympathetic fibers preferentially innervate smooth muscle cells of blood vessels located within the islet. Thus, rather than modulating endocrine cell function directly, sympathetic nerves may regulate hormone secretion in human islets by controlling local blood flow or by acting on islet regions located downstream. PMID:21723503

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

PubMed Central

Hurtado-Zavala, Joaquin I.; Ramachandran, Binu; Ahmed, Saheeb; Halder, Rashi; Bolleyer, Christiane; Awasthi, Ankit; Stahlberg, Markus A.; Wagener, Robin J.; Anderson, Kristin; Drenan, Ryan M.; Lester, Henry A.; Miwa, Julie M.; Staiger, Jochen F.; Fischer, Andre; Dean, Camin

2017-01-01

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity. PMID:28722015

Divergent Hox Coding and Evasion of Retinoid Signaling Specifies Motor Neurons Innervating Digit Muscles

PubMed Central

Mendelsohn, Alana I.; Dasen, Jeremy S.; Jessell, Thomas M.

2017-01-01

Summary The establishment of spinal motor neuron subclass diversity is achieved through developmental programs that are aligned with the organization of muscle targets in the limb. The evolutionary emergence of digits represents a specialized adaptation of limb morphology, yet it remains unclear how the specification of digit-innervating motor neuron subtypes parallels the elaboration of digits. We show that digit-innervating motor neurons can be defined by selective gene markers and distinguished from other LMC neurons by the expression of a variant Hox gene repertoire and by the failure to express a key enzyme involved in retinoic acid synthesis. This divergent developmental program is sufficient to induce the specification of digit-innervating motor neurons, emphasizing the specialized status of digit control in the evolution of skilled motor behaviors. Our findings suggest that the emergence of digits in the limb is matched by distinct mechanisms for specifying motor neurons that innervate digit muscles. PMID:28190640

Successful Implantation of Bioengineered, Intrinsically Innervated, Human Internal Anal Sphincter

PubMed Central

Raghavan, Shreya; Gilmont, Robert R.; Miyasaka, Eiichi A.; Somara, Sita; Srinivasan, Shanthi; Teitelbaum, Daniel H; Bitar, Khalil N.

2011-01-01

Background & Aims To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS, to emulate sphincteric physiology, in vitro. Methods We co-cultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1−/− mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components. Results The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and pre-implant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic EFS-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components. Conclusion Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence. PMID:21463628

The Influence of Dopaminergic Striatal Innervation on Upper Limb Locomotor Synergies

PubMed Central

Isaias, Ioannis U.; Volkmann, Jens; Marzegan, Alberto; Marotta, Giorgio; Cavallari, Paolo; Pezzoli, Gianni

2012-01-01

To determine the role of striatal dopaminergic innervation on upper limb synergies during walking, we measured arm kinematics in 13 subjects with Parkinson disease. Patients were recruited according to several inclusion criteria to represent the best possible in vivo model of dopaminergic denervation. Of relevance, we included only subjects with normal spatio-temporal parameters of the stride and gait speed to avoid an impairment of upper limbs locomotor synergies as a consequence of gait impairment per se. Dopaminergic innervation of the striatum was measured by FP-CIT and SPECT. All patients showed a reduction of gait-associated arms movement. No linear correlation was found between arm ROM reduction and contralateral dopaminergic putaminal innervation loss. Still, a partition analysis revealed a 80% chance of reduced arm ROM when putaminal dopamine content loss was >47%. A significant correlation was described between the asymmetry indices of the swinging of the two arms and dopaminergic striatal innervation. When arm ROM was reduced, we found a positive correlation between upper-lower limb phase shift modulation (at different gait velocities) and striatal dopaminergic innervation. These findings are preliminary evidence that dopaminergic striatal tone plays a modulatory role in upper-limb locomotor synergies and upper-lower limb coupling while walking at different velocities. PMID:23236504

Role of intrahepatic innervation in regulating the activity of liver cells

PubMed Central

Streba, Letitia Adela Maria; Vere, Cristin Constantin; Ionescu, Alin Gabriel; Streba, Costin Teodor; Rogoveanu, Ion

2014-01-01

Liver innervation comprises sympathetic, parasympathetic and peptidergic nerve fibers, organized as either afferent or efferent nerves with different origins and roles. Their anatomy and physiology have been studied in the past 30 years, with different results published over time. Hepatocytes are the main cell population of the liver, making up almost 80% of the total liver volume. The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways. In this short review, we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population, how it influences their metabolism and functions, and how different receptors and transmitters are involved in this complex process. PMID:24672643

Prevalence and elimination of sibling neurite convergence in motor units supplying neonatal and adult mouse skeletal muscle.

PubMed

Teriakidis, Adrianna; Willshaw, David J; Ribchester, Richard R

2012-10-01

During development, neurons form supernumerary synapses, most of which are selectively pruned leading to stereotyped patterns of innervation. During the development of skeletal muscle innervation, or its regeneration after nerve injury, each muscle fiber is transiently innervated by multiple motor axon branches but eventually by a single branch. The selective elimination of all but one branch is the result of competition between the converging arbors. It is thought that motor neurons initially innervate muscle fibers randomly, but that axon branches from the same neuron (sibling branches) do not converge to innervate the same muscle fiber. However, random innervation would result in many neonatal endplates that are co-innervated by sibling branches. To investigate whether this occurs we examined neonatal levator auris longus (LAL) and 4th deep lumbrical (4DL) muscles, as well as adult reinnervated deep lumbrical muscles (1-4) in transgenic mice expressing yellow fluorescent protein (YFP) as a reporter. We provide direct evidence of convergence of sibling neurites within single fluorescent motor units, both during development and during regeneration after nerve crush. The incidence of sibling neurite convergence was 40% lower in regeneration and at least 75% lower during development than expected by chance. Therefore, there must be a mechanism that decreases the probability of its occurrence. As sibling neurite convergence is not seen in normal adults, or at later timepoints in regeneration, synapse elimination must also remove convergent synaptic inputs derived from the same motor neuron. Mechanistic theories of synaptic competition should now accommodate this form of isoaxonal plasticity. Copyright © 2012 Wiley Periodicals, Inc.

The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. II. Projection patterns of the nerves associated with the pro- and mesothorax and the pharyngeal complex.

PubMed

Schoofs, Andreas; Hanslik, Ulrike; Niederegger, Senta; Heinzel, Hans-Georg; Spiess, Roland

2010-08-01

We describe the anatomy of the nerves that project from the central nervous system (CNS) to the pro- and mesothoracic segments and the cephalopharyngeal skeleton (CPS) for third instar Calliphora larvae. Due to the complex branching pattern we introduce a nomenclature that labels side branches of first and second order. Two fine nerves that were not yet described are briefly introduced. One paired nerve projects to the ventral arms (VAs) of the CPS. The second, an unpaired nerve, projects to the ventral surface of the cibarial part of the esophagus (ES). Both nerves were tentatively labeled after the structures they innervate. The antennal nerve (AN) innervates the olfactory dorsal organ (DO). It contains motor pathways that project through the frontal connectives (FC) to the frontal nerve (FN) and innervate the cibarial dilator muscles (CDM) which mediate food ingestion. The maxillary nerve (MN) innervates the sensory terminal organ (TO), ventral organ (VO), and labial organ (LO) and comprises the motor pathways to the mouth hook (MH) elevator, MH depressor, and the labial retractor (LR) which opens the mouth cavity. An anastomosis of unknown function exists between the AN and MN. The prothoracic accessory nerve (PaN) innervates a dorsal protractor muscle of the CPS and sends side branches to the aorta and the bolwig organ (BO) (stemmata). In its further course, this nerve merges with the prothoracic nerve (PN). The architecture of the PN is extremely complex. It innervates a set of accessory pharyngeal muscles attached to the CPS and the body wall musculature of the prothorax. Several anastomoses exist between side branches of this nerve which were shown to contain motor pathways. The mesothoracic nerve (MeN) innervates a MH accessor and the longitudinal and transversal body wall muscles of the second segment. J. Morphol. 271:969-979, 2010. (c) 2010 Wiley-Liss, Inc.

Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

PubMed Central

Michaloudi, H C; Papadopoulos, G C

1996-01-01

Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation.

PubMed

Imnadze, Guram; Balzer, Stefan; Meyer, Baerbel; Neumann, Joerg; Krech, Rainer Horst; Thale, Joachim; Franz, Norbert; Warnecke, Henning; Awad, Khaled; Hayek, Salim S; Devireddy, Chandan

2016-12-01

Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter <300 µm a score = 1; 3-4 nerves or nerve diameter 300-599 µm a score = 2, and >4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P < 0.001). Medial (1.30 ± 0.59) and distal (1.39 ± 0.62) innervation was higher than the proximal (1.17 ± 0.55) segments (p < 0.001). When divided in quadrants, the anterior (1.52 ± 0.96) and superior (1.71 ± 0.89) segments were more innervated compared to posterior (0.96 ± 0.72) and inferior (0.90 ± 0.68) segments (P < 0.001). That the right renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the renal nerves we created a novel innervation score. On average the right renal arteries were significantly more densely innervated than the left renal arteries, the anterior and superior segments were significantly more innervated compared to the posterior and inferior segments, absolute innervation scores in the proximal third of the left or right renal arteries were always lower when compared to distal segments. These findings may enhance catheter-based renal arterial denervation procedural strategy and outcomes. © 2016, Wiley Periodicals, Inc.

Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43)

PubMed Central

Gajda, Mariusz; Litwin, Jan A; Cichocki, Tadeusz; Timmermans, Jean-Pierre; Adriaensen, Dirk

2005-01-01

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16–21 and in neonates and juvenile individuals on postnatal days (PD) 1–28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes. PMID:16050900

Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination

PubMed Central

Sahel, Aurélia; Ortiz, Fernando C.; Kerninon, Christophe; Maldonado, Paloma P.; Angulo, María Cecilia; Nait-Oumesmar, Brahim

2015-01-01

Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While OPCs are innervated by unmyelinated axons in the normal brain, the fate of such synaptic contacts after demyelination is still unclear. By combining electrophysiology and immunostainings in different transgenic mice expressing fluorescent reporters, we studied the synaptic innervation of OPCs in the model of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic innervation of reactivated OPCs in the lesion was revealed by the presence of AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D confocal reconstructions and synaptic junctions observed by electron microscopy. Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the existence of glutamatergic axon-OPC contacts in post-mortem MS lesions. Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a drastic decrease in spontaneous synaptic activity of OPCs early after demyelination that was not caused by an impaired conduction of compound action potentials. A reduction in synaptic connectivity was confirmed by the lack of VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation phase in lesions, the proportion of innervated OPCs rapidly recovers, although the frequency of spontaneous synaptic currents did not reach control levels. In conclusion, our results demonstrate that newly-generated OPCs do not receive synaptic inputs during their active proliferation after demyelination, but gain synapses during the remyelination process. Hence, glutamatergic synaptic inputs may contribute to inhibit OPC proliferation and might have a physiopathological relevance in demyelinating disorders. PMID:25852473

Clinical anatomy of the chorda tympani: a systematic review.

PubMed

McManus, L J; Dawes, P J D; Stringer, M D

2011-11-01

The chorda tympani is at risk of iatrogenic injury throughout its course. This paper reviews the clinical anatomy of the nerve in adults. Systematic literature review. Relevant English-language articles were identified using five electronic databases and one search engine. Data from approximately 70 scientific papers were supplemented with information from selected reference texts. The anatomy of the chorda tympani differs from standard descriptions, particularly regarding its exit from the middle ear and area of lingual innervation. Whilst it is known to convey taste sensation from the anterior two-thirds of the tongue and parasympathetic innervation to the submandibular and sublingual salivary glands, the chorda tympani probably has additional sensory and secretomotor functions. A detailed understanding of the anatomy of the chorda tympani may help to reduce the risk of iatrogenic injury during head, neck and middle-ear surgery, and to explain the variable consequences of such injury.

The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin.

PubMed

Hidaka, Takanori; Ogawa, Eisaku; Kobayashi, Eri H; Suzuki, Takafumi; Funayama, Ryo; Nagashima, Takeshi; Fujimura, Taku; Aiba, Setsuya; Nakayama, Keiko; Okuyama, Ryuhei; Yamamoto, Masayuki

2017-01-01

Atopic dermatitis is increasing worldwide in correlation with air pollution. Various organic components of pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes express constitutively active AhR and that develop atopic-dermatitis-like phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose product (the neurotrophic factor artemin) was responsible for epidermal hyper-innervation that led to hypersensitivity to pruritus. The activation of AhR via air pollutants induced expression of artemin, alloknesis, epidermal hyper-innervation and inflammation. AhR activation and ARTN expression were positively correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in keratinocytes senses environmental stimuli and elicits an atopic-dermatitis pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via activation of AhR.

Tracking the allocation of attention using human pupillary oscillations

PubMed Central

Naber, Marnix; Alvarez, George A.; Nakayama, Ken

2013-01-01

The muscles that control the pupil are richly innervated by the autonomic nervous system. While there are central pathways that drive pupil dilations in relation to arousal, there is no anatomical evidence that cortical centers involved with visual selective attention innervate the pupil. In this study, we show that such connections must exist. Specifically, we demonstrate a novel Pupil Frequency Tagging (PFT) method, where oscillatory changes in stimulus brightness over time are mirrored by pupil constrictions and dilations. We find that the luminance–induced pupil oscillations are enhanced when covert attention is directed to the flicker stimulus and when targets are correctly detected in an attentional tracking task. These results suggest that the amplitudes of pupil responses closely follow the allocation of focal visual attention and the encoding of stimuli. PFT provides a new opportunity to study top–down visual attention itself as well as identifying the pathways and mechanisms that support this unexpected phenomenon. PMID:24368904

Vagal Intramuscular Arrays: The Specialized Mechanoreceptor Arbors That Innervate the Smooth Muscle Layers of the Stomach Examined in the Rat

PubMed Central

Powley, Terry L.; Hudson, Cherie N.; McAdams, Jennifer L.; Baronowsky, Elizabeth A.; Phillips, Robert J.

2016-01-01

The fundamental roles that the stomach plays in ingestion and digestion notwithstanding, little morphological information is available on vagal intramuscular arrays (IMAs), the afferents that innervate gastric smooth muscle. To characterize IMAs better, rats were given injections of dextran biotin in the nodose ganglia, and, after tracer transport, stomach whole mounts were collected. Specimens were processed for avidin–biotin permanent labeling, and subsets of the whole mounts were immunohistochemically processed for c-Kit or stained with cuprolinic blue. IMAs (n = 184) were digitized for morphometry and mapping. Throughout the gastric muscle wall, IMAs possessed common phenotypic features. Each IMA was generated by a parent neurite arborizing extensively, forming an array of multiple (mean = 212) branches averaging 193 μm in length. These branches paralleled, and coursed in apposition with, bundles of muscle fibers and interstitial cells of Cajal. Individual arrays averaged 4.3 mm in length and innervated volumes of muscle sheet, presumptive receptive fields, averaging 0.1 mm3. Evaluated by region and by muscle sheet, IMAs displayed architectural adaptations to the different loci. A subset (32%) of circular muscle IMAs issued specialized polymorphic collaterals to myenteric ganglia, and a subset (41%) of antral longitudinal muscle IMAs formed specialized net endings associated with the serosal boundary. IMAs were concentrated in regional patterns that correlated with the unique biomechanical adaptations of the stomach, specifically proximal stomach reservoir functions and antral emptying operations. Overall, the structural adaptations and distributions of the IMAs were consonant with the hypothesized stretch receptor roles of the afferents. PMID:26355387

Neural changes in periapical lesions after systemic steroids in the ferret.

PubMed

Holland, G R

1993-06-01

This study was intended to clarify the relationship between the neural changes which occur around the apex of the ferret canine after pulpectomy and the inflammatory process induced by the procedure. In 12 young adult ferrets, under general anesthesia, the pulps in the mandibular canine teeth were removed and replaced with gutta percha and Grossman's sealer. Six of the animals were treated with dexamethasone to reduce the inflammatory response. Three months later, the animals, again under general anesthesia, were perfused with a fixative mixture. Three unoperated animals that had not been treated with dexamethasone were also perfused. The mandibular canine teeth and their supporting tissues were removed, processed, and serially sectioned. Three-dimensional reconstructions of the periapical lesions in each animal were assembled and their volumes measured. The density of innervation in the periapical region was estimated. The mean lesion volume in the pulpectomized animals not treated with dexamethasone was 3.54 (+/- 2.27) mm3 and in the dexamethasone-treated animals 1.33 (+/- 1.31) mm3. The differences were statistically significant when tested by the Mann-Whitney U test (p < 0.01). Bacteria were not seen within any of the lesions. The innervation density beneath the canines in the pulpectomized animals not treated with dexamethasone was 164 units per mm2 (+/- 80) and in the steroid-treated animals 151 +/- 68 units per mm2. In the control, untreated animals, the innervation density was 22 +/- 10 units per mm2. The difference between the steroid-treated pulpectomized animals and the untreated pulpectomized animals was not statistically significant (p > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Innervation pattern of the suprascapular nerve within supraspinatus: a three-dimensional computer modeling study.

PubMed

Hermenegildo, J A; Roberts, S L; Kim, S Y

2014-05-01

The relationship between the innervation pattern of the suprascapular nerve (SSN) and the muscle architecture of supraspinatus has not been thoroughly investigated. The supraspinatus is composed of two architecturally distinct regions: anterior and posterior. Each of these regions is further subdivided into three parts: superficial, middle and deep. The purpose of this study was to investigate the course of the SSN throughout the volume of supraspinatus and to relate the intramuscular branches to the distinct regions and parts of the supraspinatus. The SSN was dissected in thirty formalin embalmed cadaveric specimens and digitized throughout the muscle volume in six of those specimens. The digitized data were modeled using Autodesk(®) Maya(®) 2011. The three-dimensional (3D) models were used to relate the intramuscular innervation pattern to the muscle and tendon architecture defined by Kim et al. (2007, Clin Anat 20:648-655). The SSN bifurcated into two main trunks: medial and lateral. All parts of the anterior region were predominantly innervated by the medial trunk and its proximal and medial branches, whereas all parts of the posterior region predominantly by the lateral trunk and its posterolateral and/or posteromedial branches. The posterior region also received innervation from the proximal branch of the medial trunk in half of the specimens. These findings provide evidence that the anterior and posterior regions are distinct with respect to their innervation. The 3D map of the innervation pattern will aid in planning future clinical studies investigating muscle activation patterns and provide insight into possible injury of the nerve with supraspinatus pathology and surgical techniques. Copyright © 2013 Wiley Periodicals, Inc.

Distributions of nerve and muscle fibre types in locust jumping muscle.

PubMed

Hoyle, G

1978-04-01

Muscle fibres of the locust extensor tibiae (jumping muscle) were examined by interference microscopy and by electron microscopy. The electrical responses of single fibres and the mechanical responses of bundles or selected regions to the nerve fibres were examined. Four axons innervate the muscle: fast (FETi), slow (SETi), common inhibitor (CI) and dorsal unpaired median (DUMETi). Their distributions were examined by combined electrophysiological tracing and EM sectioning. The mean diameter of muscle fibres in different regions varies from 40 to 140 micrometer and is related to the local leg thickness rather than muscle fibre type. The fine structure of a fibre is related to its innervation. Fibres innervated by FETi but not SETi are of fast type ultrastructurally. Fibres innervated by SETi but not by FETi are of slow type ultrastructurally. Fibres innervated by both axons are generally intermediate between the extremes though more nearly of fast type than slow. Distal slow muscle fibres have much slower relaxation rates than do proximal ones. The most proximal bundles are of mixed muscle fibre type. There is an abrupt transition from a mixed population to homogeneous fast type, in the muscle units immediately distal to the most proximal bundles. This transition is associated with the presence of DUMETi terminals on some of the fibres distal to the transition point. There are no SETi endings on these same fibres. Fibres innervated by both SETi and FETi are scattered throughout the leg, but are commonest in the dorsal bundles. The percentage of these increases progressively passing distally. The most distal muscle fibres are innervated by SETi but not by FETi. It is concluded that different regions of the muscle will play different roles functionally since they are differentially sensitive to the pattern of SETi discharge.

Origin of the styloglossus muscle in the human fetus

PubMed Central

Mérida-Velasco, J R; Rodríguez-Vazquez, J F; de la Cuadra Blanco, C; Sánchez-Montesinos, I; Mérida-Velasco, J A

2006-01-01

The origin of the styloglossus muscle was histologically studied bilaterally in nine human fetuses (18 sides). In all cases, the muscle originated in Reichert's cartilage, which gives rise to the temporal styloid process. We identified three types of variation: type A, an accessory muscle fascicle originating from the mandibular angle, found in 7 cases (12 sides); type B, where the styloglossus muscle was attached to the mandibular angle by fibrous tracts, found in three cases (4 sides); and type C, where an accessory muscle fascicle arose from the fibrous tract connecting Reichert's cartilage to the mandibular angle; found in one case. In all cases (2 sides), the styloglossus muscle was innervated by the hypoglossal nerve. Relationships between the styloglossus muscle and vasculonervous elements of the prestyloid and retrostyloid spaces were analysed. PMID:16637887

Direct Interaction between Autonomic Nerves and the Immune System.

DTIC Science & Technology

1986-08-05

between the autonomic nervous system and the immune system in young adult male C3H and BALB/c mice. Evidence from our laboratory and others has revealed...noted in the distribution and appearance of noradrenergic varicosities along the vasculature or within the parenchyma in the spleens of adult C3H, BALB...months of age. There also were some age- related differences in thymic innervation and lymph node innervation, but the splenic innervation in adults

ELECTROPHYSIOLOGY OF ELECTRIC ORGAN IN GYMNOTUS CARAPO

PubMed Central

Bennett, Michael V. L.; Grundfest, Harry

1959-01-01

The electric organ of G. carapo is formed by linearly arrayed electroplaques which lie in four tubes on each side of the fish. In one tube the electroplaques are innervated on their rostral surfaces, in the others on the caudal. Both surfaces of each electroplaque produce spikes, and either can be excited alone by a suitably oriented externally applied stimulating current. The innervated surface, however, has a lower threshold, and in the normal organ activity, which is a continuous discharge at 35 to 60/sec., it is always fired first by the large neurally evoked postsynaptic potential. The spike of the innervated face then fires the opposite face. The potential recorded external to the innervated face is initially negative and becomes positive when the other face fires. The potential outside the other face is inverted. The p.s.p.'s are electrically inexcitable, have short duration, and are augmented by hyperpolarization. A single electroplaque is innervated by several nerve fibers, which produce summative p.s.p.'s. Homosynaptic facilitation of p.s.p.'s is common. The synapses are cholinoceptive. The organ discharge begins with synchronized activity in the rostrally innervated electroplaques. After a brief interval, the electroplaques in the other three tubes fire. The organ discharge therefore is triphasic, resulting from the summation of the two diphasic components that are oppositely directed and asynchronous. Observations on the sensory role of the organ are included. PMID:13654750

Ionic currents and charge movements in organ-cultured rat skeletal muscle.

PubMed

Hollingworth, S; Marshall, M W; Robson, E

1984-12-01

The middle of the fibre voltage-clamp technique was used to measure ionic currents and non-linear charge movements in intact, organ-cultured (in vitro denervated) mammalian fast-twitch (rat extensor digitorum longus) muscle fibres. Muscle fibres organ cultured for 4 days can be used as electrophysiological and morphological models for muscles in vivo denervated for the same length of time. Sodium currents in organ-cultured muscle fibres are similar to innervated fibres except that in the temperature range 0-20 degrees C (a) in the steady state, the voltage distribution of inactivation in cultured fibres is shifted negatively some 20 mV; (b) at the same temperature and membrane potential, the time constant of inactivation in cultured fibres is about twice that of innervated fibres. Potassium currents in innervated and cultured fibres at 15 degrees C can be fitted with the Hodgkin-Huxley n variable raised to the second power. Despite the large range we would estimate that the maximum value of the steady-state potassium conductance of cultured fibres is about one-half that of innervated fibres. The estimated maximum amount of charge moved in cultured fibre is about one-third that in innervated fibres. Compared to innervated fibres, culturing doubles the kinetics of the decay phase of charge movement. The possibility of a negative shift of the voltage distribution of charge movements in cultured fibres is discussed.

Nogo Receptor Homolog NgR2 Expressed in Sensory DRG Neurons Controls Epidermal Innervation by Interaction with Versican

PubMed Central

Bäumer, Bastian E.; Kurz, Antje; Borrie, Sarah C.; Sickinger, Stephan; Dours-Zimmermann, María T.; Zimmermann, Dieter R.

2014-01-01

Primary sensory afferents of the dorsal root ganglion (DRG) that innervate the skin detect a wide range of stimuli, such as touch, temperature, pain, and itch. Different functional classes of nociceptors project their axons to distinct target zones within the developing skin, but the molecular mechanisms that regulate target innervation are less clear. Here we report that the Nogo66 receptor homolog NgR2 is essential for proper cutaneous innervation. NgR2−/− mice display increased density of nonpeptidergic nociceptors in the footpad and exhibit enhanced sensitivity to mechanical force and innocuous cold temperatures. These sensory deficits are not associated with any abnormality in morphology or density of DRG neurons. However, deletion of NgR2 renders nociceptive nonpeptidergic sensory neurons insensitive to the outgrowth repulsive activity of skin-derived Versican. Biochemical evidence shows that NgR2 specifically interacts with the G3 domain of Versican. The data suggest that Versican/NgR2 signaling at the dermo-epidermal junction acts in vivo as a local suppressor of axonal plasticity to control proper density of epidermal sensory fiber innervation. Our findings not only reveal the existence of a novel and unsuspected mechanism regulating epidermal target innervation, but also provide the first evidence for a physiological role of NgR2 in the peripheral nervous system. PMID:24478347

Nogo receptor homolog NgR2 expressed in sensory DRG neurons controls epidermal innervation by interaction with Versican.

PubMed

Bäumer, Bastian E; Kurz, Antje; Borrie, Sarah C; Sickinger, Stephan; Dours-Zimmermann, María T; Zimmermann, Dieter R; Bandtlow, Christine E

2014-01-29

Primary sensory afferents of the dorsal root ganglion (DRG) that innervate the skin detect a wide range of stimuli, such as touch, temperature, pain, and itch. Different functional classes of nociceptors project their axons to distinct target zones within the developing skin, but the molecular mechanisms that regulate target innervation are less clear. Here we report that the Nogo66 receptor homolog NgR2 is essential for proper cutaneous innervation. NgR2(-/-) mice display increased density of nonpeptidergic nociceptors in the footpad and exhibit enhanced sensitivity to mechanical force and innocuous cold temperatures. These sensory deficits are not associated with any abnormality in morphology or density of DRG neurons. However, deletion of NgR2 renders nociceptive nonpeptidergic sensory neurons insensitive to the outgrowth repulsive activity of skin-derived Versican. Biochemical evidence shows that NgR2 specifically interacts with the G3 domain of Versican. The data suggest that Versican/NgR2 signaling at the dermo-epidermal junction acts in vivo as a local suppressor of axonal plasticity to control proper density of epidermal sensory fiber innervation. Our findings not only reveal the existence of a novel and unsuspected mechanism regulating epidermal target innervation, but also provide the first evidence for a physiological role of NgR2 in the peripheral nervous system.

Renal denervation in male rats with heart failure improves ventricular sympathetic nerve innervation and function

PubMed Central

Pinkham, Maximilian I.; Loftus, Michael T.; Amirapu, Satya; Guild, Sarah-Jane; Quill, Gina; Woodward, William R.; Habecker, Beth A.

2017-01-01

Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, P < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart. PMID:28052866

BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section.

PubMed

Meng, Lingbin; Huang, Tao; Sun, Chengsan; Hill, David L; Krimm, Robin

2017-07-01

Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was unilaterally sectioned causing a loss of both taste buds and neurons, irrespective of BDNF levels. Eight weeks after nerve section, however, regeneration was differentially affected by Bdnf deletion. In control mice, there was regeneration of the chorda tympani nerve and taste buds reappeared with innervation. In contrast, few taste buds were reinnervated in mice lacking normal Bdnf expression such that taste bud number remained low. In all genotypes, taste buds that were reinnervated were normal-sized, but non-innervated taste buds remained small and atrophic. On the side of the tongue contralateral to the nerve section, taste buds for some genotypes became larger and all taste buds remained innervated. Our findings suggest that BDNF is required for nerve regeneration following gustatory nerve section. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase correlated adequate afferent action potentials as a drive of human spinal oscillators.

PubMed

Schalow, G

1993-12-01

1. By recording, with 2 pairs of wire electrodes, single-fibre action potentials (APs) from lower sacral nerve roots of a brain-dead human and a patient with spinal cord lesion, impulse patterns of afferent APs and impulse trains of oscillatory firing motoneurons could be identified and correlated. 2. Two highly activated secondary muscle spindle afferents increased and decreased their activity at about 0.3 Hz. The duration of the doublet interspike interval of a secondary spindle afferent fibre showed no correlation to the oscillation period of the motoneuron. 3. A continuously oscillatory firing motoneuron innervating the external and sphincter showed more transient breaks with the reduction of the number of phase correlated APs from 2 spindle afferents, indicating a looser oscillation. A transient brake of a 157 msec period alpha 2-oscillation could be correlated to the shift of a interspike interval distribution peak from 150 to 180 msec of the adequate afferent input, which suggests a transient loss of the necessary phase relation. 4. Oscillatory firing alpha 2-motoneurons innervating the external bladder and anal sphincters fired independently according to their phase correlated APs from the urinary bladder stretch receptor and muscle spindle afferents respectively; the bladder motoneuron slightly inhibited the anal motoneuron. 5. Receptors of the afferents and innervation sites of oscillatory firing motoneurons could be located within the urinary tract and the anal canal.

Temporal identity in axonal target layer recognition.

PubMed

Petrovic, Milan; Hummel, Thomas

2008-12-11

The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division but also connection diversity of projecting neurons.

Noradrenergic and cholinergic innervation of the bone marrow.

PubMed

Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

2002-07-01

Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

Follicle Microstructure and Innervation Vary between Pinniped Micro- and Macrovibrissae.

PubMed

Mattson, Erin E; Marshall, Christopher D

2016-01-01

Histological data from terrestrial, semiaquatic, and fully aquatic mammal vibrissa (whisker) studies indicate that follicle microstructure and innervation vary across the mystacial vibrissal array (i.e. medial microvibrissae to lateral macrovibrissae). However, comparative data are lacking, and current histological studies on pinniped vibrissae only focus on the largest ventrolateral vibrissae. Consequently, we investigated the microstructure, medial-to-lateral innervation, and morphometric trends in harp seal (Pagophilus groenlandicus) vibrissal follicle-sinus complexes (F-SCs). The F-SCs were sectioned either longitudinally or in cross-section and stained with a modified Masson's trichrome stain (microstructure) or Bodian's silver stain (innervation). All F-SCs exhibited a tripartite blood organization system. The dermal capsule thickness, the distribution of major branches of the deep vibrissal nerve, and the hair shaft design were more symmetrical in medial F-SCs, but these features became more asymmetrical as the F-SCs became more lateral. Overall, the mean axon count was 1,221 ± 422.3 axons/F-SC and mean axon counts by column ranged from 550 ± 97.4 axons/F-SC (medially, column 11) to 1,632 ± 173.2 axons/F-SC (laterally, column 2). These values indicate a total of 117,216 axons innervating the entire mystacial vibrissal array. The mean axon count of lateral F-SCs was 1,533 ± 192.9 axons/ F-SC, which is similar to values reported in the literature for other pinniped F-SCs. Our data suggest that conventional studies that only examine the largest ventrolateral vibrissae may overestimate the total innervation by ∼20%. However, our study also accounts for variation in quantification methods and shows that conventional analyses likely only overestimate innervation by ∼10%. The relationship between axon count and cross-sectional F-SC surface area was nonlinear, and axon densities were consistent across the snout. Our data indicate that harp seals exhibit microstructural and innervational differences between their microvibrissae (columns 8-11) and macrovibrissae (columns 1-7). We hypothesize that this feature is conserved among pinnipeds and may result in functional compartmentalization within their mystacial vibrissal arrays. © 2016 S. Karger AG, Basel.

Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

NASA Technical Reports Server (NTRS)

Baird, Richard A.; Schuff, N. R.

1994-01-01

Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely contacted Type B and Type C hair cells, particularly on the outer rows of the medial striola. Afferents supplying more central striolar regions innervated fewer Type B and larger numbers of Type E and Type F hair cells. Striolar afferents with thin parent axons largely supplied Type E hair cells with bulbed kniocilia in the innermost striolar rows.

Identification of neurons that express ghrelin receptors in autonomic pathways originating from the spinal cord.

PubMed

Furness, John B; Cho, Hyun-Jung; Hunne, Billie; Hirayama, Haruko; Callaghan, Brid P; Lomax, Alan E; Brock, James A

2012-06-01

Functional studies have shown that subsets of autonomic preganglionic neurons respond to ghrelin and ghrelin mimetics and in situ hybridisation has revealed receptor gene expression in the cell bodies of some preganglionic neurons. Our present goal has been to determine which preganglionic neurons express ghrelin receptors by using mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter for the ghrelin receptor (also called growth hormone secretagogue receptor). The retrograde tracer Fast Blue was injected into target organs of reporter mice under anaesthesia to identify specific functional subsets of postganglionic sympathetic neurons. Cryo-sections were immunohistochemically stained by using anti-EGFP and antibodies to neuronal markers. EGFP was detected in nerve terminal varicosities in all sympathetic chain, prevertebral and pelvic ganglia and in the adrenal medulla. Non-varicose fibres associated with the ganglia were also immunoreactive. No postganglionic cell bodies contained EGFP. In sympathetic chain ganglia, most neurons were surrounded by EGFP-positive terminals. In the stellate ganglion, neurons with choline acetyltransferase immunoreactivity, some being sudomotor neurons, lacked surrounding ghrelin-receptor-expressing terminals, although these terminals were found around other neurons. In the superior cervical ganglion, the ghrelin receptor terminals innervated subgroups of neurons including neuropeptide Y (NPY)-immunoreactive neurons that projected to the anterior chamber of the eye. However, large NPY-negative neurons projecting to the acini of the submaxillary gland were not innervated by EGFP-positive varicosities. In the celiaco-superior mesenteric ganglion, almost all neurons were surrounded by positive terminals but the VIP-immunoreactive terminals of intestinofugal neurons were EGFP-negative. The pelvic ganglia contained groups of neurons without ghrelin receptor terminal innervation and other groups with positive terminals around them. Ghrelin receptors are therefore expressed by subgroups of preganglionic neurons, including those of vasoconstrictor pathways and of pathways controlling gut function, but are absent from some other neurons, including those innervating sweat glands and the secretomotor neurons that supply the submaxillary salivary glands.

Imaging three-dimensional innervation zone distribution in muscles from M-wave recordings

NASA Astrophysics Data System (ADS)

Zhang, Chuan; Peng, Yun; Liu, Yang; Li, Sheng; Zhou, Ping; Zev Rymer, William; Zhang, Yingchun

2017-06-01

Objective. To localize neuromuscular junctions in skeletal muscles in vivo which is of great importance in understanding, diagnosing and managing of neuromuscular disorders. Approach. A three-dimensional global innervation zone imaging technique was developed to characterize the global distribution of innervation zones, as an indication of the location and features of neuromuscular junctions, using electrically evoked high-density surface electromyogram recordings. Main results. The performance of the technique was evaluated in the biceps brachii of six intact human subjects. The geometric centers of the distributions of the reconstructed innervation zones were determined with a mean distance of 9.4  ±  1.4 cm from the reference plane, situated at the medial epicondyle of the humerus. A mean depth was calculated as 1.5  ±  0.3 cm from the geometric centers to the closed points over the skin. The results are consistent with those reported in previous histology studies. It was also found that the volumes and distributions of the reconstructed innervation zones changed as the stimulation intensities increased until the supramaximal muscle response was achieved. Significance. Results have demonstrated the high performance of the proposed imaging technique in noninvasively imaging global distributions of the innervation zones in the three-dimensional muscle space in vivo, and the feasibility of its clinical applications, such as guiding botulinum toxin injections in spasticity management, or in early diagnosis of neurodegenerative progression of amyotrophic lateral sclerosis.

How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse

PubMed Central

SUZUKI, Maasa; EBARA, Satomi; KOIKE, Taro; TONOMURA, Sotatsu; KUMAMOTO, Kenzo

2012-01-01

Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4–54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10–32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1–3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement. PMID:23229751

How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse.

PubMed

Suzuki, Maasa; Ebara, Satomi; Koike, Taro; Tonomura, Sotatsu; Kumamoto, Kenzo

2012-01-01

Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4-54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10-32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1-3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement.

Autonomic innervation of the muscles in the wall of the bladder and proximal urethra of male rats.

PubMed Central

Watanabe, H; Yamamoto, T Y

1979-01-01

The muscular coat of the body of the rat bladder is innervated almost exclusively by cholinergic endings:adrenergic endings are rare. In the inner longitudinal muscle layer of the proximal urethra, 53% of 310 autonomic nerve endings observed in close relation to the smooth muscle cells were adrenergic and the remaining 47% cholinergic. The middle circular muscle layer of the proximal urethra was innervated predominantly by adrenergic endings: in this layer 86% of the total of 335 endings examined wre regarded as adrenergic. A similar predominantly adrenergic innervation was noted in the outer longitudinal layer of the proximal urethra. A number of striated muscle fibres arose from the outermost striated muscle layer of the proximal urethra and intruded deeply into the outer and middle smooth muscle layers. These intruding striated muscle fibres also received direct autonomic (mostly adrenergic) innervation. The significance of these findings in relation to the physiology of the lower urinary tracts is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:489473

Dopaminergic neurons encode a distributed, asymmetric representation of temperature in Drosophila.

PubMed

Tomchik, Seth M

2013-01-30

Dopaminergic circuits modulate a wide variety of innate and learned behaviors in animals, including olfactory associative learning, arousal, and temperature-preference behavior. It is not known whether distinct or overlapping sets of dopaminergic neurons modulate these behaviors. Here, I have functionally characterized the dopaminergic circuits innervating the Drosophila mushroom body with in vivo calcium imaging and conditional silencing of genetically defined subsets of neurons. Distinct subsets of PPL1 dopaminergic neurons innervating the vertical lobes of the mushroom body responded to decreases in temperature, but not increases, with rapidly adapting bursts of activity. PAM neurons innervating the horizontal lobes did not respond to temperature shifts. Ablation of the antennae and maxillary palps reduced, but did not eliminate, the responses. Genetic silencing of dopaminergic neurons innervating the vertical mushroom body lobes substantially reduced behavioral cold avoidance, but silencing smaller subsets of these neurons had no effect. These data demonstrate that overlapping dopaminergic circuits encode a broadly distributed, asymmetric representation of temperature that overlays regions implicated previously in learning, memory, and forgetting. Thus, diverse behaviors engage overlapping sets of dopaminergic neurons that encode multimodal stimuli and innervate a single anatomical target, the mushroom body.

Deficient Vasoactive Intestinal Peptide Innervation in the Sweat Glands of Cystic Fibrosis Patients

NASA Astrophysics Data System (ADS)

Heinz-Erian, Peter; Dey, Richard D.; Flux, Marinus; Said, Sami I.

1985-09-01

The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide--containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.

Endodontic periapical lesion-induced mental nerve paresthesia

PubMed Central

Shadmehr, Elham; Shekarchizade, Neda

2015-01-01

Paresthesia is a burning or prickling sensation or partial numbness, resulting from neural injury. The symptoms can vary from mild neurosensory dysfunction to total loss of sensation in the innervated area. Only a few cases have described apical periodontitis to be the etiological factor of impaired sensation in the area innervated by the inferior alveolar and mental nerves. The aim of the present paper is to report a case of periapical lesion-induced paresthesia in the innervation area of the mental nerve, which was successfully treated with endodontic retreatment. PMID:25878687

Behavior-dependent specialization of identified hippocampal interneurons

PubMed Central

Lapray, Damien; Lasztoczi, Balint; Lagler, Michael; Viney, Tim James; Katona, Linda; Valenti, Ornella; Hartwich, Katja; Borhegyi, Zsolt; Somogyi, Peter; Klausberger, Thomas

2012-01-01

A large variety of GABAergic interneurons control information processing in hippocampal circuits governing the formation of neuronal representations. Whether distinct hippocampal interneuron types contribute differentially to information-processing during behavior is not known. We employed a novel technique for recording and labeling interneurons and pyramidal cells in drug-free, freely-moving rats. Recorded parvalbumin-expressing basket interneurons innervate somata and proximal pyramidal cell dendrites, whereas nitric-oxide-synthase- and neuropeptide-Y-expressing ivy cells provide synaptic and extrasynaptic dendritic modulation. Basket and ivy cells showed distinct spike timing dynamics, firing at different rates and times during theta and ripple oscillations. Basket but not ivy cells changed their firing rates during movement, sleep and quiet wakefulness, suggesting that basket cells coordinate cell assemblies in a behavioral state-contingent manner, whereas persistently-firing ivy cells might control network excitability and homeostasis. Different interneuron types provide GABA to specific subcellular domains at defined times and rates, thus differentially controlling network activity during behavior. PMID:22864613

Anatomy and Neurophysiology of Cough

PubMed Central

Canning, Brendan J.; Chang, Anne B.; Bolser, Donald C.; Smith, Jaclyn A.; Mazzone, Stuart B.; Adams, Todd M.; Altman, Kenneth W.; Barker, Alan F.; Birring, Surinder S.; Blackhall, Fiona; Bolser, Donald, C.; Boulet, Louis-Philippe; Braman, Sidney S.; Brightling, Christopher; Callahan-Lyon, Priscilla; Canning, Brendan; Chang, Anne Bernadette; Coeytaux, Remy; Cowley, Terrie; Davenport, Paul; Diekemper, Rebecca L.; Ebihara, Satoru; El Solh, Ali A.; Escalante, Patricio; Feinstein, Anthony; Field, Stephen K.; Fisher, Dina; French, Cynthia T.; Gibson, Peter; Gold, Philip; Grant, Cameron; Harding, Susan M.; Harnden, Anthony; Hill, Adam T.; Irwin, Richard S.; Kahrilas, Peter J.; Keogh, Karina A.; Lane, Andrew P.; Lewis, Sandra Zelman; Lim, Kaiser; Malesker, Mark A.; Mazzone, Peter; Mazzone, Stuart; Molasiotis, Alex; Murad, M. Hassan; Newcombe, Peter; Nguyen, Huong Q.; Oppenheimer, John; Prezant, David; Pringsheim, Tamara; Restrepo, Marcos I.; Rosen, Mark; Rubin, Bruce; Ryu, Jay H.; Smith, Jaclyn; Tarlo, Susan M.; Turner, Ronald B.; Vertigan, Anne; Wang, Gang; Weir, Kelly

2014-01-01

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human. PMID:25188530

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction.

PubMed

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Besalduch, Nuria; Priego, Merche; Tomàs, Josep

2010-08-16

We use immunocytochemistry to show that the trophic molecule glial cell line-derived neurotrophic factor (GDNF) and its receptor GDNF family receptor alpha-1 (GFRalpha-1) are present in both neonatal (P6) and adult (P45) rodent neuromuscular junctions (NMJ) colocalized with several synaptic markers. However, incubation with exogenous GDNF (10-200ng/ml, 1-3h), does not affect spontaneous ACh release. Moreover, GDNF does not change the size of the evoked ACh release from the weak and the strong axonal inputs on dually innervated postnatal endplates nor in the most developed singly-innervated synapses at P6 and P45. Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Nanofibers implant functionalized by neural growth factor as a strategy to innervate a bioengineered tooth.

PubMed

Eap, Sandy; Bécavin, Thibault; Keller, Laetitia; Kökten, Tunay; Fioretti, Florence; Weickert, Jean-Luc; Deveaux, Etienne; Benkirane-Jessel, Nadia; Kuchler-Bopp, Sabine

2014-03-01

Current strategies for jaw reconstruction require multiple procedures, to repair the bone defect, to offer sufficient support, and to place the tooth implant. The entire procedure can be painful and time-consuming, and the desired functional repair can be achieved only when both steps are successful. The ability to engineer combined tooth and bone constructs, which would grow in a coordinated fashion with the surrounding tissues, could potentially improve the clinical outcomes and also reduce patient suffering. A unique nanofibrous and active implant for bone-tooth unit regeneration and also the innervation of this bioengineered tooth are demonstrated. A nanofibrous polycaprolactone membrane is functionalized with neural growth factor, along with dental germ, and tooth innervation follows. Such innervation allows complete functionality and tissue homeostasis of the tooth, such as dentinal sensitivity, odontoblast function, masticatory forces, and blood flow. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bilateral innervation of syringeal muscles by the hypoglossal nucleus in the jungle crow (Corvus macrorhynchos).

PubMed

Tsukahara, Naoki; Kamata, Naoki; Nagasawa, Miyuki; Sugita, Shoei

2009-08-01

Bird vocalizations are produced by contractions of syringeal muscles, which are controlled by the hypoglossal nucleus. In oscines, syringeal muscles are controlled by the hypoglossal nucleus ipsilaterally, whereas syringeal innervation is bilateral in non-oscines. We have determined the course of hypoglossal nerves in the jungle crow Corvus macrorhynchos. Our results indicate a cross-over of the hypoglossal nerve from the left side to the right side on the trachea 7 mm rostral to the Musculus sternotrachealis. We also investigated the innervation of the syringeal muscles of jungle crows from the hypoglossal nucleus using the horseradish peroxidase (HRP) method. After HRP was injected into the syringeal muscles on each side, HRP-labeled cells were found bilaterally in the hypoglossal nerve. These results suggest that the syringeal muscles of jungle crows are innervated bilaterally from the hypoglossal nucleus, although these birds are categorized as oscines.

Bilateral innervation of syringeal muscles by the hypoglossal nucleus in the jungle crow (Corvus macrorhynchos)

PubMed Central

Tsukahara, Naoki; Kamata, Naoki; Nagasawa, Miyuki; Sugita, Shoei

2009-01-01

Bird vocalizations are produced by contractions of syringeal muscles, which are controlled by the hypoglossal nucleus. In oscines, syringeal muscles are controlled by the hypoglossal nucleus ipsilaterally, whereas syringeal innervation is bilateral in non-oscines. We have determined the course of hypoglossal nerves in the jungle crow Corvus macrorhynchos. Our results indicate a cross-over of the hypoglossal nerve from the left side to the right side on the trachea 7 mm rostral to theMusculus sternotrachealis. We also investigated the innervation of the syringeal muscles of jungle crows from the hypoglossal nucleus using the horseradish peroxidase (HRP) method. After HRP was injected into the syringeal muscles on each side, HRP-labeled cells were found bilaterally in the hypoglossal nerve. These results suggest that the syringeal muscles of jungle crows are innervated bilaterally from the hypoglossal nucleus, although these birds are categorized as oscines. PMID:19490396

The luteinizing hormone-releasing hormone (LHRH) systems in the rat brain.

PubMed

Witkin, J W; Paden, C M; Silverman, A J

1982-12-01

Immunocytochemical procedures on thick, unembedded sections were used to visualize the neurons and their processes that contain LHRH-immunoreactive material in the rat central nervous system (CNS). In animals pretreated with colchicine (75 micrograms, intraventricularly), cell bodies could be observed as far anterior as the olfactory bulb and posterior to the retrochiasmatic area of the basal hypothalamus. Several new observations for the rat were made in this study, including LHRH neurons in the accessory olfactory bulb and other olfactory-related structures, and in the anterior hippocampus and the induseum griseum. As in studies from other laboratories, we observed many LHRH cells in the periventricular medial preoptic area, diagonal band of Broca and septal nuclei, and fewer positive cells in the anterior hypothalamic area and the region of the supraoptic commissure. The LHRH fibers from all of these cells are widely dispersed in the CNS. In addition to the dense innervation of the median eminence, positive fibers are found innervating other circumventricular organs, coursing close to the ependymal wall of the ventricular system or in close association with cerebral arteries and areas of the pia mater and subarachnoid space. LHRH fibers may also innervate neurons in several regions of the CNS. A novel projection of LHRH fibers for the rat was found originating from supracallosal neurons and coursing through both cingulate and neocortex. The possible distribution of efferents from each LHRH cell group is discussed.

Functional compatibility between Purkinje cell axon branches and their target neurons in the cerebellum.

PubMed

Yang, Zhilai; Chen, Na; Ge, Rongjing; Qian, Hao; Wang, Jin-Hui

2017-09-22

A neuron sprouts an axon, and its branches to innervate many target neurons that are divergent in their functions. In order to efficiently regulate the diversified cells, the axon branches should differentiate functionally to be compatible with their target neurons, i.e., a function compatibility between presynaptic and postsynaptic partners. We have examined this hypothesis by using electrophysiological method in the cerebellum, in which the main axon of Purkinje cell projected to deep nucleus cells and the recurrent axons innervated the adjacent Purkinje cells. The fidelity of spike propagation is superior in the recurrent branches than the main axon. The capabilities of encoding spikes and processing GABAergic inputs are advanced in Purkinje cells versus deep nucleus cells. The functional differences among Purkinje's axonal branches and their postsynaptic neurons are preset by the variable dynamics of their voltage-gated sodium channels. In addition, activity strengths between presynaptic and postsynaptic partners are proportionally correlated, i.e., active axonal branches innervate active target neurons, or vice versa. The physiological impact of the functional compatibility is to make the neurons in their circuits to be activated appropriately. In conclusion, each cerebellar Purkinje cell sprouts the differentiated axon branches to be compatible with the diversified target cells in their functions, in order to construct the homeostatic and efficient units for their coordinated activity in neural circuits.

Functional compatibility between Purkinje cell axon branches and their target neurons in the cerebellum

PubMed Central

Qian, Hao; Wang, Jin-Hui

2017-01-01

A neuron sprouts an axon, and its branches to innervate many target neurons that are divergent in their functions. In order to efficiently regulate the diversified cells, the axon branches should differentiate functionally to be compatible with their target neurons, i.e., a function compatibility between presynaptic and postsynaptic partners. We have examined this hypothesis by using electrophysiological method in the cerebellum, in which the main axon of Purkinje cell projected to deep nucleus cells and the recurrent axons innervated the adjacent Purkinje cells. The fidelity of spike propagation is superior in the recurrent branches than the main axon. The capabilities of encoding spikes and processing GABAergic inputs are advanced in Purkinje cells versus deep nucleus cells. The functional differences among Purkinje's axonal branches and their postsynaptic neurons are preset by the variable dynamics of their voltage-gated sodium channels. In addition, activity strengths between presynaptic and postsynaptic partners are proportionally correlated, i.e., active axonal branches innervate active target neurons, or vice versa. The physiological impact of the functional compatibility is to make the neurons in their circuits to be activated appropriately. In conclusion, each cerebellar Purkinje cell sprouts the differentiated axon branches to be compatible with the diversified target cells in their functions, in order to construct the homeostatic and efficient units for their coordinated activity in neural circuits. PMID:29069799

Assessment of cardiac sympathetic neuronal function using PET imaging.

PubMed

Bengel, Frank M; Schwaiger, Markus

2004-01-01

The autonomic nervous system plays a key role for regulation of cardiac performance, and the importance of alterations of innervation in the pathophysiology of various heart diseases has been increasingly emphasized. Nuclear imaging techniques have been established that allow for global and regional investigation of the myocardial nervous system. The guanethidine analog iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic mapping of presynaptic sympathetic innervation and is available today for imaging on a broad clinical basis. Not much later than MIBG, positron emission tomography (PET) has also been established for characterizing the cardiac autonomic nervous system. Although PET is methodologically demanding and less widely available, it provides substantial advantages. High spatial and temporal resolution along with routinely available attenuation correction allows for detailed definition of tracer kinetics and makes noninvasive absolute quantification a reality. Furthermore, a series of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands are available. Those are often more physiologic than MIBG and well understood with regard to their tracer physiologic properties. PET imaging of sympathetic neuronal function has been successfully applied to gain mechanistic insights into myocardial biology and pathology. Available tracers allow dissection of processes of presynaptic and postsynaptic innervation contributing to cardiovascular disease. This review summarizes characteristics of currently available PET tracers for cardiac neuroimaging along with the major findings derived from their application in health and disease.

Constructing a new nigrostriatal pathway in the Parkinsonian model with bridged neural transplantation in substantia nigra.

PubMed

Zhou, F C; Chiang, Y H; Wang, Y

1996-11-01

The physical repair and restoration of a completely damaged pathway in the brain has not been achieved previously. In a previous study, using excitatory amino acid bridging and fetal neural transplantation, we demonstrated that a bridged mesencephalic transplant in the substantia nigra generated an artificial nerve pathway that reinnervated the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the current study, we report that a bridged mesencephalic transplant can anatomically, neurochemically, and functionally reinstate the 6-OHDA-eradicated nigro-striatal pathway. An excitatory amino acid, kainic acid, laid down in a track during the transplant generated a trophic environment that effectively guided the robust growth of transplanted neuronal fibers in a bundle to innervate the distal striatum. Growth occurred at the remarkable speed of approximately 200 microm/d. Two separate and distinct types of dopamine (DA) innervation from the transplant have been achieved for the first time: (1) DA innervation of the striatum, and (2) DA innervation of the pars reticularis of the substantia nigra. In addition, neuronal tracing revealed that reciprocal connections were achieved. The grafted DA neurons in the SNr innervated the host's striatum, whereas the host's striatal neurons, in turn, innervated the graft within 3-8 weeks. Electrochemical volt- ammetry recording revealed the restoration of DA release and clearance in a broad striatal area associated with the DA reinnervation. Furthermore, the amphetamine-induced rotation was attenuated, which indicates that the artificial pathways were motor functional. This study provides additional evidences that our bridged transplantation technique is a potential means for the repair of a completely damaged neuronal pathway.

Efferent innervation to the auditory basilar papilla of scincid lizards.

PubMed

Wibowo, Erik; Brockhausen, Jennifer; Köppl, Christine

2009-09-01

Hair cells of the inner ear of vertebrates are innervated by afferent neurons that transmit sensory information to the brain as well as efferent neurons that receive feedback from the brainstem. The function of the efferent feedback system is poorly understood and may have changed during evolution when different tetrapod groups acquired sensitivity to airborne sound and extended their hearing ranges to higher frequencies. Lizards show a unique subdivision of their basilar papilla (homologous to the mammalian organ of Corti) into a low-frequency (<1 kHz) and a high-frequency (approximately 1-5 kHz) region. The high-frequency region was reported to have lost its efferent innervation, suggesting it was insignificant or even functionally detrimental at higher frequencies. We re-examined the innervation to the basilar papilla of five species of Australian scincid lizards, by using immunohistochemistry. Anti-choline acetyltransferase (ChAT) was used as an efferent marker. Co-localization with anti-synaptic vesicle protein 2 confirmed the synaptic identity of label. Cholinergic terminals were observed along the whole length of the basilar papilla, including the regions that had previously been described as devoid of efferent innervation. However, there was a clear decrease in terminal density from apical, low-frequency to basal, high-frequency locations. Our findings suggest that efferent innervation is a general feature of the hair cells in the basilar papilla of lizards, irrespective of tonotopic location. This re-enforces the notion that efferent feedback control of hair cells is a fundamental and important property of all vertebrate hearing organs. (c) 2009 Wiley-Liss, Inc.

Induced formation and maturation of acetylcholine receptor clusters in a defined 3D bio-artificial muscle.

PubMed

Wang, Lin; Shansky, Janet; Vandenburgh, Herman

2013-12-01

Dysfunction of the neuromuscular junction is involved in a wide range of muscular diseases. The development of neuromuscular junction through which skeletal muscle is innervated requires the functional modulation of acetylcholine receptor (AchR) clustering on myofibers. However, studies on AchR clustering in vitro are mostly done on monolayer muscle cell culture, which lacks a three-dimensional (3D) structure, a prominent limitation of the two-dimensional (2D) system. To enable a better understanding on the structure-function correlation underlying skeletal muscle innervation, a muscle system with a well-defined geometry mimicking the in vivo muscular setting is needed. Here, we report a 3D bio-artificial muscle (BAM) bioengineered from green fluorescent protein-transduced C3H murine myoblasts as a novel in vitro tissue-based model for muscle innervation studies. Our cell biological and molecular analysis showed that this BAM is structurally similar to in vivo muscle tissue and can reach the perinatal differentiation stage, higher than does 2D culture. Effective clustering and morphological maturation of AchRs on BAMs induced by agrin and laminin indicate the functional activity and plasticity of this BAM system toward innervation. Taken together, our results show that the BAM provides a favorable 3D environment that at least partially recapitulates real physiological skeletal muscle with regard to innervation. With a convenience of fabrication and manipulation, this 3D in vitro system offers a novel model for studying mechanisms underlying skeletal muscle innervation and testing therapeutic strategies for relevant nervous and muscular diseases.

The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior

PubMed Central

Zhao, Jun; Levy, Dan

2014-01-01

Headaches are thought to result from the activation and sensitization of nociceptors that innervate deep cephalic tissues. A large body of evidence supports the view that some types of headaches originate intracranially, from activation of sensory neurons that innervate the cranial meninges. However the notion of an extracranial origin of headaches continues to be entertained, although the identity of deep extracranial cephalic tissues which might contribute to headaches remains elusive. Here we employed anatomical, electrophysiological, and behavioral approaches in rats to test the hypothesis that the sensory innervation of the calvarial periosteum is nociceptive. Neural tracing indicated that the calvarial periosteum overlying the frontal and parietal bones is innervated primarily by small and medium-sized neurons in the trigeminal ganglion’s ophthalmic division. In vivo single unit recording in the trigeminal ganglion revealed that calvarial periosteal afferents have slowly conducting axons, are mechanosensitive and respond to inflammatory mediators, consistent with a nociceptive function. Two distinct neuronal populations were distinguished based on their peripheral axonal trajectory: one that reached the periosteum through extracranial branches of the trigeminal nerve, and another that took an intracranial trajectory, innervating the cranial dura and apparently reaching the periosteum via the calvarial sutures. In behavioral studies, inflammatory stimulation of these afferents promoted periorbital tactile hypersensitivity, a sensory change linked to primary headaches. Activation and sensitization of calvarial periosteal afferents could play a role in mediating primary headaches of extracranial and perhaps also intracranial origin, as well as secondary headaches such as post-craniotomy and post-traumatic headaches. Targeting calvarial periosteal afferents may be effective in ameliorating these headaches. PMID:24769138

Histologic Anatomy of the Anterior Vagina and Urethra.

PubMed

Mazloomdoost, Donna; Westermann, Lauren B; Mutema, George; Crisp, Catrina C; Kleeman, Steven D; Pauls, Rachel N

Vaginal and urethral histology is important to understanding the pathophysiology of the pelvic floor. En bloc removal of 4 female cadaveric pelvises was performed, with 18 to 25 serial sections obtained from each. The vaginal and urethral lengths were divided into distal and proximal sections; urethra was divided into anterior and posterior segments as well. Innervation and vasculature were qualified as small and large and quantified per high-power field. The mean vaginal length was 7.45 cm, and the mean urethral length was 3.38 cm. A distinct vaginal fibromuscular layer was noted, without evidence of a dense sheet of continuous collagen. An epithelial, lamina propria, and muscular layer surrounded the urethral lumen. Adipose and loose fibroconnective tissue separated the urethra from the anterior vagina in 41% of slides. Nerves and vasculature were concentrated in the lamina propria. More small nerves and vessels were grossly seen compared with larger counterparts in both the vagina and urethra. No significant differences in layer thickness, innervation, or vasculature were observed along the vaginal length. The posterior urethra had greater innervation than did the anterior (P = 0.012). The distal posterior urethra had more large vessels than did the proximal posterior urethra (P = 0.03). No other differences were noted in urethral sections. A vaginal fibromuscular layer was confirmed, refuting a true fascia. Innervation and vasculature were quantitatively the same along the anterior vagina. However, the posterior urethra had greater innervation than did anterior and is most innervated proximally. Nerve and vascular histology may relate to pelvic floor disorder etiology.

Parasympathetic, sympathetic, and sensory interactions in the iris: nerve growth factor regulates cholinergic ciliary ganglion innervation in vivo.

PubMed

Kessler, J A

1985-10-01

Interactions between peptidergic sensory nerves, noradrenergic sympathetic nerves, and cholinergic parasympathetic fibers were examined in the rat iris. The putative peptide neurotransmitter, substance P (SP), was used as an index of the trigeminal sensory innervation, tyrosine hydroxylase (TH) activity served to monitor the sympathetic fibers, and choline acetyltransferase (CAT) activity was used as an index of the parasympathetic innervation. Destruction of the sympathetic innervation by neonatal administration of 6-hydroxydopamine resulted in increased SP development and a smaller increase in CAT activity in the iris. Moreover, trigeminal ablation resulted in an increase in both TH and CAT activities. Finally, ciliary ganglionectomy resulted in increased SP and a smaller increase in TH activity in the iris. Administration of nerve growth factor (NGF) into the anterior chamber substantially increased both SP and TH activity in the iris and also increased CAT activity to a lesser extent. Moreover, administration of anti-NGF into the anterior chamber prevented both the sympathectomy-induced increases in SP and CAT, and the increases in TH and CAT activities after trigeminal ablation, suggesting that NGF mediated these increases. These observations suggest that the sympathetic, sensory, and parasympathetic innervations of the iris interact by altering availability of NGF elaborated by the iris. Regulation of iris CAT activity was examined in greater detail. Injection of the cholinergic toxin, AF64A, into the anterior chamber concurrently with ablation of the sympathetic and sensory innervations paradoxically increased CAT activity, whereas AF64A alone decreased CAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of innervation of the lacrimal gland with clinical application.

PubMed

Scott, Gabriel; Balsiger, Heather; Kluckman, Matthew; Fan, Jerry; Gest, Thomas

2014-11-01

Parasympathetic stimulation of the lacrimal gland is responsible for tear production, and this innervation originates from fibers conveyed in the facial nerve. After synapse in the pterygopalatine ganglion, postsynaptic parasympathetic fibers travel within the zygomatic and zygomaticotemporal nerves (ZTN) into the orbit. As described in most anatomy texts, ZTN communicates with the lacrimal nerve (LN) posterior to the gland and then secretomotor fibers enter the gland. This study was performed to gain a better understanding of the innervation of the lacrimal gland. Seventeen cadaver heads were bisected for a total of 34 sides, which then underwent dissection of the superolateral orbital region to observe the course for the LN and ZTN. Three variations of the course of the LN and ZTN were found. In 20 (60.6%) dissections it was documented that the ZTN entered directly into the lacrimal gland with no communication with the LN. In 12 (36.4%) of the bisected heads, ZTN had both a direct connection into the gland and a communicating branch with the LN. In only one (3.0%) bisected head, ZTN communicated with the LN before entering the gland as it is commonly described in anatomy texts. Our study reveals that the ZTN usually takes a different course than is classically described in most anatomy textbooks. A greater understanding of the typical course these nerves take may help surgeons identify them more easily and avoid damaging them. © 2014 Wiley Periodicals, Inc.

Pirt contributes to uterine contraction-induced pain in mice.

PubMed

Wang, Changming; Wang, Zhongli; Yang, Yan; Zhu, Chan; Wu, Guanyi; Yu, Guang; Jian, Tunyu; Yang, Niuniu; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Liu, Qin; Guan, Yun; Dong, Xinzhong; Duan, Jinao; Tang, Zongxiang

2015-09-17

Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt (+/+) and Pirt (-/-) mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt (-/-) mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt (+/+) and Pirt (-/-) mice. We found that the writhing responses were less intensive in Pirt (-/-) mice than in Pirt (+/+) mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt (-/-) mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain.

Expression of vesicular glutamate transporters in sensory and autonomic neurons innervating the mouse bladder.

PubMed

Brumovsky, Pablo R; Seal, Rebecca P; Lundgren, Kerstin H; Seroogy, Kim B; Watanabe, Masahiko; Gebhart, G F

2013-06-01

VGLUTs, which are essential for loading glutamate into synaptic vesicles, are present in various neuronal systems. However, to our knowledge the expression of VGLUTs in neurons innervating the bladder has not yet been analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons. We analyzed the expression of VGLUT1, VGLUT2 and calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled primary afferent and autonomic neurons of BALB/c mice after injecting fast blue in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in which VGLUT3 is identified by enhanced green fluorescent protein detection. Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2 immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2 immunoreactive nerves were detected in the bladder dome and trigone, and the urethra. VGLUT1 immunoreactive nerves were discretely present. We present what are to our knowledge novel data on VGLUT expression in sensory and autonomic neurons innervating the mouse bladder. The frequent association of VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests interactions between glutamatergic and peptidergic neurotransmissions, potentially influencing commonly perceived sensations in the bladder, such as discomfort and pain. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Ultrastructure of identified fast excitatory, slow excitatory and inhibitory neuromuscular junctions in the locust.

PubMed

Titmus, M J

1981-06-01

The specialized jumping muscle of the locust, the metathoracic extensor tibiae (ETi), is innervated by four physiologically different motoneurons, including FETi, a phasic excitor, SETi, a tonic excitor, and CI, a tonic common inhibitor. FETi neuromuscular junctions were examined in three phasic ETi bundles innervated by FETi. FETi terminals were characterized by patchy contacts on to granular sarcoplasm. The ETi accessory extensor, innervated by both SETi and CI, contains two morphologically different types of axon ending. When this muscle was soaked in horseradish peroxidase, stimulation of SETi led to selective uptake in vesicles in terminals similar to those of FETi axons but containing smaller vesicles, while stimulation by CI caused increased uptake into terminals with more extensive contact directly on to fibrillar sarcoplasm. As has been observed in excitatory and inhibitory synapses in some crustacean and vertebrate nervous systems, the synaptic vesicles in the locust excitatory endings are round and electron-lucent while those in the inhibitory endings are more irregular in shape. The tonic neuromuscular junctions, SETi and CI, are more densely packed with vesicles, larger in cross-sectional area and appear to be of more complex shape than the smaller, vesicle-sparse, phasic FETi terminals. Following long duration stimulation at 10 Hz, the tonic neuromuscular junctions showed little morphological change. FETi endings, which fatigue within minutes at the same stimulation frequency, showed a 20% decrease in synaptic vesicle density and an increase in irregularly shaped membrane inclusions.

Dopaminergic and Cholinergic Modulations of Visual-Spatial Attention and Working Memory: Insights from Molecular Genetic Research and Implications for Adult Cognitive Development

ERIC Educational Resources Information Center

Stormer, Viola S.; Passow, Susanne; Biesenack, Julia; Li, Shu-Chen

2012-01-01

Attention and working memory are fundamental for selecting and maintaining behaviorally relevant information. Not only do both processes closely intertwine at the cognitive level, but they implicate similar functional brain circuitries, namely the frontoparietal and the frontostriatal networks, which are innervated by cholinergic and dopaminergic…

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients.

PubMed

Manitt, C; Eng, C; Pokinko, M; Ryan, R T; Torres-Berrío, A; Lopez, J P; Yogendran, S V; Daubaras, M J J; Grant, A; Schmidt, E R E; Tronche, F; Krimpenfort, P; Cooper, H M; Pasterkamp, R J; Kolb, B; Turecki, G; Wong, T P; Nestler, E J; Giros, B; Flores, C

2013-12-17

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.

The subgenual organ complex in the cave cricket Troglophilus neglectus (Orthoptera: Rhaphidophoridae): comparative innervation and sensory evolution

PubMed Central

Strauß, Johannes; Stritih, Nataša; Lakes-Harlan, Reinhard

2014-01-01

Comparative studies of the organization of nervous systems and sensory organs can reveal their evolution and specific adaptations. In the forelegs of some Ensifera (including crickets and tettigoniids), tympanal hearing organs are located in close proximity to the mechanosensitive subgenual organ (SGO). In the present study, the SGO complex in the non-hearing cave cricket Troglophilus neglectus (Rhaphidophoridae) is investigated for the neuronal innervation pattern and for organs homologous to the hearing organs in related taxa. We analyse the innervation pattern of the sensory organs (SGO and intermediate organ (IO)) and its variability between individuals. In T. neglectus, the IO consists of two major groups of closely associated sensilla with different positions. While the distal-most sensilla superficially resemble tettigoniid auditory sensilla in location and orientation, the sensory innervation does not show these two groups to be distinct organs. Though variability in the number of sensory nerve branches occurs, usually either organ is supplied by a single nerve branch. Hence, no sensory elements clearly homologous to the auditory organ are evident. In contrast to other non-hearing Ensifera, the cave cricket sensory structures are relatively simple, consistent with a plesiomorphic organization resembling sensory innervation in grasshoppers and stick insects. PMID:26064547

The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

PubMed Central

Huettl, Rosa-Eva; Hanuschick, Philipp; Amend, Anna-Lena; Alberton, Paolo; Aszodi, Attila; Huber, Andrea B.

2016-01-01

ABSTRACT Correct innervation of the main respiratory muscle in mammals, namely the thoracic diaphragm, is a crucial pre-requisite for the functionality of this muscle and the viability of the entire organism. Systemic impairment of Sema3A–Npn-1 (Npn-1 is also known as NRP1) signaling causes excessive branching of phrenic nerves in the diaphragm and into the central tendon region, where the majority of misguided axons innervate ectopic musculature. To elucidate whether these ectopic muscles are a result of misguidance of myoblast precursors due to the loss of Sema3A–Npn-1 signaling, we conditionally ablated Npn-1 in somatic motor neurons, which led to a similar phenotype of phrenic nerve defasciculation and, intriguingly, also formation of innervated ectopic muscles. We therefore hypothesize that ectopic myocyte fusion is caused by additional factors released by misprojecting growth cones. Slit2 and its Robo receptors are expressed by phrenic motor axons and migrating myoblasts, respectively, during innervation of the diaphragm. In vitro analyses revealed a chemoattractant effect of Slit2 on primary diaphragm myoblasts. Thus, we postulate that factors released by motor neuron growth cones have an influence on the migration properties of myoblasts during establishment of the diaphragm. PMID:27466379

Differential TRPV1 and TRPV2 Channel Expression in Dental Pulp

PubMed Central

Gibbs, J.L.; Melnyk, J.L.; Basbaum, A.I.

2011-01-01

Hypersensitivity to thermal and mechanical stimuli can occur in painful pulpitis. To explore the neuro-anatomical basis of heat and mechanical sensitivity, we evaluated expression of TRPV1 (heat) and TRPV2 (heat/mechanical) channels in the cell bodies and terminal arborizations of neurons that innervate the dental pulp (DP) and periodontal tissues (PDL). We report that ~50% of trigeminal ganglion (TG) neurons retrogradely labeled from the DP express TRPV2, and this was significantly greater than the general expression of this channel in the TG (15%) and slightly more than what is expressed in the PDL by retrograde labeling (40%). The TRPV1 receptor, however, was less prevalent in neurons innervating the DP than their general expression in the TG (17% vs. 26%) and was more extensively expressed in neurons innervating the PDL (26%). Co-labeling studies showed that 70% of neurons that innervate the DP are myelinated. Approximately 1/3 of the retrogradely labeled neurons from the DP were calcitonin-gene-related-peptide-positive (peptide-expressing), but very few expressed the IB4 marker of non-peptidergic unmyelinated afferents. These findings suggest that the DP has a unique neurochemical innervation with regard to TRP receptor expression, which has significant implications for the mechanisms contributing to odontogenic pain and management strategies. PMID:21406609

Differential TRPV1 and TRPV2 channel expression in dental pulp.

PubMed

Gibbs, J L; Melnyk, J L; Basbaum, A I

2011-06-01

Hypersensitivity to thermal and mechanical stimuli can occur in painful pulpitis. To explore the neuro-anatomical basis of heat and mechanical sensitivity, we evaluated expression of TRPV1 (heat) and TRPV2 (heat/mechanical) channels in the cell bodies and terminal arborizations of neurons that innervate the dental pulp (DP) and periodontal tissues (PDL). We report that ~50% of trigeminal ganglion (TG) neurons retrogradely labeled from the DP express TRPV2, and this was significantly greater than the general expression of this channel in the TG (15%) and slightly more than what is expressed in the PDL by retrograde labeling (40%). The TRPV1 receptor, however, was less prevalent in neurons innervating the DP than their general expression in the TG (17% vs. 26%) and was more extensively expressed in neurons innervating the PDL (26%). Co-labeling studies showed that 70% of neurons that innervate the DP are myelinated. Approximately 1/3 of the retrogradely labeled neurons from the DP were calcitonin-gene-related-peptide-positive (peptide-expressing), but very few expressed the IB4 marker of non-peptidergic unmyelinated afferents. These findings suggest that the DP has a unique neurochemical innervation with regard to TRP receptor expression, which has significant implications for the mechanisms contributing to odontogenic pain and management strategies.

Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

PubMed

Biddinger, Jessica E; Fox, Edward A

2014-07-30

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

Recent Advances in Insect Olfaction, Specifically Regarding the Morphology and Sensory Physiology of Antennal Sensilla of the Female Sphinx Moth Manduca sexta

PubMed Central

SHIELDS, VONNIE D.C.; HILDEBRAND, JOHN G.

2008-01-01

The antennal flagellum of female Manduca sexta bears eight sensillum types: two trichoid, two basiconic, one auriculate, two coeloconic, and one styliform complex sensilla. The first type of trichoid sensillum averages 34 μm in length and is innervated by two sensory cells. The second type averages 26 μm in length and is innervated by either one or three sensory cells. The first type of basiconic sensillum averages 22 μm in length, while the second type averages 15 μm in length. Both types are innervated by three bipolar sensory cells. The auriculate sensillum averages 4 μm in length and is innervated by two bipolar sensory cells. The coeloconic type-A and type-B both average 2 μm in length. The former type is innervated by five bipolar sensory cells, while the latter type, by three bipolar sensory cells. The styliform complex sensillum occurs singly on each annulus and averages 38-40 μm in length. It is formed by several contiguous sensilla. Each unit is innervated by three bipolar sensory cells. A total of 2,216 sensilla were found on a single annulus (annulus 21) of the flagellum. Electrophysiological responses from type-A trichoid sensilla to a large panel of volatile odorants revealed three different subsets of olfactory receptor cells (ORCs). Two subsets responded strongly to only a narrow range of odorants, while the third responded strongly to a broad range of odorants. Anterograde labeling of ORCs from type-A trichoid sensilla revealed that their axons projected mainly to two large female glomeruli of the antennal lobe. PMID:11754510

Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

PubMed

Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

2018-04-01

To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

Anatomy of psoas muscle innervation: Cadaveric study.

PubMed

Mahan, Mark A; Sanders, Luke E; Guan, Jian; Dailey, Andrew T; Taylor, William; Morton, David A

2017-05-01

Hip flexion weakness is relatively common after lateral transpsoas surgery. Persistent weakness may result from injury to the innervation of the psoas major muscles (PMMs); however, anatomical texts have conflicting descriptions of this innervation, and the branching pattern of the nerves within the psoas major, particularly relative to vertebral anatomy, has not been described. The authors dissected human cadavers to describe the branching pattern of nerves supplying the PMMs. Sixteen embalmed cadavers were dissected, and the fine branching pattern of the innervation to the PMM was studied in 24 specimens. The number of branches and width and length of each branch of nerves to the PMMs were quantified. Nerve branches innervating the PMMs arose from spinal nerve levels L1-L4, with an average of 6.3 ± 1.1 branches per muscle. The L1 nerve branch was the least consistently present, whereas L2 and L3 branches were the most robust, the most numerous, and always present. The nerve branches to the psoas major commonly crossed the intervertebral (IV) disc obliquely prior to ramification within the muscle; 76%, 80%, and 40% of specimens had a branch to the PMM cross the midportion of the L2-3, L3-4, and L4-5 IV discs, respectively. The PMMs are segmentally innervated from the L2-L4 ventral rami branches, where these branches course obliquely across the L2-3, L3-4, and L4-5 IV discs. Knowledge of the mapping of nerve branches to the PMMs may reduce injury and the incidence of persistent weak hip flexion during lateral transpsoas surgery. Clin. Anat. 30:479-486, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory.

PubMed

Miyazaki, Taisuke; Yamasaki, Miwako; Takeuchi, Tomonori; Sakimura, Kenji; Mishina, Masayoshi; Watanabe, Masahiko

2010-11-10

Glutamate receptor GluRδ2 is exclusively expressed in Purkinje cells (PCs) from early development and plays key roles in parallel fiber (PF) synapse formation, elimination of surplus climbing fibers (CFs), long-term depression, motor coordination, and motor learning. To address its role in adulthood, we previously developed a mouse model of drug-induced GluRδ2 ablation in adult PCs (Takeuchi et al., 2005). In that study, we demonstrated an essential role to maintain the connectivity of PF-PC synapses, based on the observation that both mismatching of presynaptic and postsynaptic specializations and disconnection of PF-PC synapses are progressively increased after GluRδ2 ablation. Here, we pursued its role for CF wiring in adult cerebellum. In parallel with the disconnection of PF-PC synapses, ascending CF branches exhibited distal extension to innervate distal dendrites of the target and neighboring PCs. Furthermore, transverse CF branches, a short motile collateral rarely forming synapses in wild-type animals, displayed aberrant mediolateral extension to innervate distal dendrites of neighboring and remote PCs. Consequently, many PCs were wired by single main CF and other surplus CFs innervating a small part of distal dendrites. Electrophysiological recording further revealed that surplus CF-EPSCs characterized with slow rise time and small amplitude emerged after GluRδ2 ablation, and increased progressively both in number and amplitude. Therefore, GluRδ2 is essential for maintaining CF monoinnervation in adult cerebellum by suppressing aberrant invasion of CF branches to the territory of PF innervation. Thus, GluRδ2 fuels heterosynaptic competition and gives PFs the competitive advantages over CFs throughout the animal's life.

Adaptations in the structure and innervation of follicle-sinus complexes to an aquatic environment as seen in the Florida manatee (Trichechus manatus latirostris).

PubMed

Sarko, Diana K; Reep, Roger L; Mazurkiewicz, Joseph E; Rice, Frank L

2007-09-20

Florida manatees are large-bodied aquatic herbivores that use large tactile vibrissae for several purposes. Facial vibrissae are used to forage in a turbid water environment, and the largest perioral vibrissae can also grasp and manipulate objects. Other vibrissae distributed over the entire postfacial body appear to function as a lateral line system. All manatee vibrissae emanate from densely innervated follicle-sinus complexes (FSCs) like those in other mammals, although proportionately larger commensurate with the caliber of the vibrissae. As revealed by immunofluorescence, all manatee FSCs have many types of C, Adelta and Abeta innervation including Merkel, club, and longitudinal lanceolate endings at the level of the ring sinus, but they lack other types such as reticular and spiny endings at the level of the cavernous sinus. As in non-whisking terrestrial species, the inner conical bodies of facial FSCs are well innervated but lack Abeta-fiber terminals. Importantly, manatee FSCs have two unique types of Abeta-fiber endings. First, all of the FSCs have exceptionally large-caliber axons that branch to terminate as novel, gigantic spindle-like endings located at the upper ring sinus. Second, facial FSCs have smaller caliber Abeta fibers that terminate in the trabeculae of the cavernous sinus as an ending that resembles a Golgi tendon organ. In addition, the largest perioral vibrissae, which are used for grasping, have exceptionally well-developed medullary cores that have a structure and dense small-fiber innervation resembling that of tooth pulp. Other features of the epidermis and upper dermis structure and innervation differ from that seen in terrestrial mammals. Copyright (c) 2007 Wiley-Liss, Inc.

Innervation of the cricothyroid muscle by the recurrent laryngeal nerve.

PubMed

Masuoka, Hiroo; Miyauchi, Akira; Yabuta, Tomonori; Fukushima, Mitsuhiro; Miya, Akihiro

2016-04-01

The recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (SLN) are generally thought to innervate the endolaryngeal muscles and the cricothyroid muscle (CTM), respectively. Meticulous anatomic studies found communication between these nerves (ie, the human communicating nerve). In this study, we report the innervation of the CTM by the RLN. We performed electromyographic studies of 50 patients during thyroidectomy (20 total and 30 hemithyroidectomies). During surgery, the external branch of the SLN, RLN, and vagus nerve were stimulated. Responses were evaluated by visual observation of the CTM and by electromyographies through needle electrodes inserted into the CTM. Seventy CTMs were evaluated. The RLN stimulation yielded both visible contractions and clear electromyographic responses (>300 µV) in 27 (39%), either response in 24 (34%), and neither response in 19 (27%) of the CTMs. The vagus stimulation gave similar results. The RLN innervated the CTM at least in 39% cases. © 2015 Wiley Periodicals, Inc. Head Neck 38: E441-E445, 2016. © 2015 Wiley Periodicals, Inc.

A light and transmission electron microscope study of the distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the zebrafish eye.

PubMed

Chapman, G B; Tarboush, R; Eagles, D A; Connaughton, V P

2009-08-01

The distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the eyes of the zebrafish, Danio rerio (Hamilton), were investigated using light and transmission electron microscopy. A comparative study of the quality of preservation provided by three different fixation procedures revealed no consistently striking general differences. However, somewhat subjectively, the fixative containing Millonig's buffer did consistently provide better fixation of myelin. Overall, nerve processes, depending on the site studied, were distributed as either (1) bundles (in the choroid near the optic nerve head and in the choroid adjacent to the limbus), (2) linear arrays (in the junction between the sclera and cartilage and in the choroid adjacent to the retina) or (3) individual units (in the choroid under the cartilage or in the sclera). Both myelinated and unmyelinated processes were identified in these locations. Myelinated processes usually contained both neurofilaments and neurotubules, but a few apparently contained only neurofilaments. Unmyelinated processes usually contained mainly neurotubules, but a few apparently contained only neurofilaments. Taken together, these findings indicate innervation of extra-retinal structures, as seen in zebrafish, is highly conserved among vertebrates, further supporting the use of zebrafish as a model for the vertebrate visual system.

Immediate effects on electromyographic activity and pressure pain thresholds after a cervical manipulation in mechanical neck pain: a randomized controlled trial.

PubMed

de Camargo, Viviane Maduro; Alburquerque-Sendín, Francisco; Bérzin, Fausto; Stefanelli, Vinicius Cobos; de Souza, Daiana P Rodrigues; Fernández-de-las-Peñas, César

2011-05-01

The purpose of this study was to identify the immediate effects of a manipulation of C5/C6 level on electromyography (EMG) of the deltoid muscle and in pressure pain thresholds (PPTs) in patients with mechanical neck pain. Thirty-seven subjects with mechanical neck pain were randomly divided into 2 groups: manipulative group, which received a cervical spine manipulation targeted to C5/C6 segment, and a control group, which did not receive any procedure. Outcomes were EMG data of the deltoid muscle (rest, isometric contraction for 5 or 30 seconds, and isotonic contraction) and PPT over upper trapezius and deltoid muscles and C5 spinous process. They were assessed before and 5 minutes after treatment by a blinded assessor. A 3-way repeated-measures analysis of variance was used to examine the effects of the manipulation. A significant group time interaction for MF at the beginning of isometric contraction for 30 seconds (F = 7.957, P = .006) was also found: the manipulative group experienced a greater increase in MF at the beginning of the isometric contraction than did the control group. A significant group time interaction was also found for root mean square during isometric contraction for 30 seconds (P = .003); however, changes were small. Patients within the manipulative group experienced an increase on PPT over the deltoid (P = .010) and C5 spinous process (P = .025), but not over upper trapezius (P = .776). Manipulation at C5/C6 level in the study participants seemed to increase EMG amplitude signal and fatigue resistance in a nonspinal (deltoid) muscle innervated by the same segment in patients with mechanical neck pain. However, these changes were relative small. An increase on PPT over those tissues innervated by the manipulated segment was also found after the manipulative procedure. Copyright © 2011 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

[Immunocytochemical study of cholinergic innervation in the neurosensory epithelia of human vestibule].

PubMed

Kong, W; Hussl, B; Schrott-Fischer, A

1998-02-01

To investigate the cholinergic innervation of the neurosensory epithelia of human vestibule. A modified preembedding immunostaining technique for immunoelectronmicroscopy was applied to this study. A polyclonal antibody to choline acetyltransferase (ChAT) was used as the marker of cholinergic fibers. ChAT-immunoreactive products were restricted to the nerve fibers and terminals which were rich in synaptic vesicles. The ChAT-immunoreactive fibers synaps with afferent chalice as well as with type II sensory hair cells. This study demonstrates that cholinergic fibers innervate the neurosensory epithelia of human vestible. The cholinergic fibers of human vestibular sensory epithelia belong to the vestibular efferent system.

Cultured embryonic non-innervated mouse muzzle is capable of generating a whisker pattern.

PubMed

Andrés, F L; Van Der Loos, H

1983-01-01

The whisker pattern on the muzzle of the mouse is mapped in the contralateral parietal neocortex, each whisker follicle projecting to its own multineuronal unit ('barrel'). To determine the role, if any, of the peripheral innervation in the establishment of the vibrissal array, we cultured non-innervated prospective whiskerpads from 9- and 10-day-old embryos, mostly on chorioallantoic membrane. The results show that skin, alone, is capable of generating the whisker pattern, thus adducing a strong argument for the hypothesis that the central brain maps have their origin in the periphery. Copyright © 1983. Published by Elsevier Ltd.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Conversion of muscle fiber types in regenerating chicken muscles following cross-reinnervation.

PubMed

Kikuchi, T; Akiba, T; Ashmore, C R

1986-01-01

Slow-tonic anterior latissimus dorsi (ALD) and fast-twitch posterior latissimus dorsi (PLD) muscles of 7 to 10-day-old White Leghorn chickens were crushed and allowed to be reinnervated by their own nerve, or crushed and transplanted to the other side and allowed to be reinnervated by the nerve of the side to which they were transplanted. Following transplantation, changes in the weight of the muscle, fiber-type composition and innervation pattern during regeneration were investigated. Normal growth rate of PLD was about twice that of ALD. Regenerating PLD, however, atrophied rapidly after crushing and denervation whether innervated by its own nerve or the other nerve type, whereas ALD reinnervated by its own nerve showed marked hypertrophy. PLD fibers transformed rapidly to fast-twitch alpha or slow-tonic (ST) fibers when they were reinnervated by PLD or ALD nerve, respectively. When ALD fibers were reinnervated by their own nerve, they differentiated into ST fibers that were surrounded by smaller immature fibers. ALD fibers were, however, resistant to complete control by fast-twitch PLD nerve and contained a large number of slow fibers (ST and beta) long after transplantation. Slow fibers in regenerates were initially multiply innervated, but later transformed into fast-twitch alpha fibers that were focally innervated. The mode of differentiation and innervation pattern of different muscle fiber types in regenerating muscles are discussed.

[Motor nerves of the face. Surgical and radiologic anatomy of facial paralysis and their surgical repair].

PubMed

Vacher, C; Cyna-Gorse, F

2015-10-01

Motor innervation of the face depends on the facial nerve for the mobility of the face, on the mandibular nerve, third branch of the trigeminal nerve, which gives the motor innervation of the masticator muscles, and the hypoglossal nerve for the tongue. In case of facial paralysis, the most common palliative surgical techniques are the lengthening temporalis myoplasty (the temporal is innervated by the mandibular nerve) and the hypoglossal-facial anastomosis. The aim of this work is to describe the surgical anatomy of these three nerves and the radiologic anatomy of the facial nerve inside the temporal bone. Then the facial nerve penetrates inside the parotid gland giving a plexus. Four branches of the facial nerve leave the parotid gland: they are called temporal, zygomatic, buccal and marginal which give innervation to the cutaneous muscles of the face. Mandibular nerve gives three branches to the temporal muscles: the anterior, intermediate and posterior deep temporal nerves which penetrate inside the deep aspect of the temporal muscle in front of the infratemporal line. The hypoglossal nerve is only the motor nerve to the tongue. The ansa cervicalis, which is coming from the superficial cervical plexus and joins the hypoglossal nerve in the submandibular area is giving the motor innervation to subhyoid muscles and to the geniohyoid muscle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy

PubMed Central

Ling, Karen K. Y.; Gibbs, Rebecca M.; Feng, Zhihua; Ko, Chien-Ping

2012-01-01

Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy. PMID:21968514

Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4.

PubMed

Ito, Akira; Nosrat, Christopher A

2009-09-01

Taste buds and the peripheral nerves innervating them are two important components of the peripheral gustatory system. They require appropriate connections for the taste system to function. Neurotrophic factors play crucial roles in the innervation of peripheral sensory organs and tissues. Both brain-derived neurotrophic factor (BDNF) null-mutated and neurotrophin-4 (NT-4) null-mutated mice exhibit peripheral gustatory deficits. BDNF and NT-4 bind to a common high affinity tyrosine kinase receptor, TrkB (NTRK-2), and a common p75 neurotrophin receptor (NGFR). We are currently using a transgenic mouse model to study peripheral taste system development and innervation in the absence of both TrkB ligands. We show that taste cell progenitors express taste cell markers during early stages of taste bud development in both BDNF(-/-)xNT-4(-/-) and wild-type mice. At early embryonic stages, taste bud progenitors express Troma-1, Shh, and Sox2 in all mice. At later stages, lack of innervation becomes a prominent feature in BDNF(-/-)xNT-4(-/-) mice leading to a decreasing number of fungiform papillae and morphologically degenerating taste cells. A total loss of vallate taste cells also occurs in postnatal transgenic mice. Our data indicate an initial independence but a later permissive and essential role for innervation in taste bud development and maintenance.

Adaptive Plasticity of Vaginal Innervation in Term Pregnant Rats

PubMed Central

Liao, Zhaohui; Smith, Peter G.

2011-01-01

Changes in reproductive status place varied functional demands on the vagina. These include receptivity to male intromission and sperm transport in estrus, barrier functions during early pregnancy, and providing a conduit for fetal passage at parturition. Peripheral innervation regulates vaginal function, which in turn may be influenced by circulating reproductive hormones. We assessed vaginal innervation in diestrus and estrus (before and after the estrous cycle surge in estrogen), and in the early (low estrogen) and late (high estrogen) stages in pregnancy. In vaginal sections from cycling rats, axons immunoreactive for the pan-neuronal marker protein gene product 9.5 (PGP 9.5) showed a small reduction at estrus relative to diestrus, but this difference did not persist after correcting for changes in target size. No changes were detected in axons immunoreactive for tyrosine hydroxylase (sympathetic), vesicular acetylcholine transporter (parasympathetic), or calcitonin gene-related peptide and transient receptor potential vanilloid type 1 (TRPV-1; sensory nociceptors). In rats at 10 days of pregnancy, innervation was similar to that observed in cycling rats. However, at 21 days of pregnancy, axons immunoreactive for PGP 9.5 and each of the subpopulation-selective markers were significantly reduced both when expressed as percentage of sectional area or after correcting for changes in target size. Because peripheral nerves regulate vaginal smooth muscle tone, blood flow, and pain sensitivity, reductions in innervation may represent important adaptive mechanisms facilitating parturition. PMID:21666101

Parasympathetic innervation of vertebrobasilar arteries: is this a potential clinical target?

PubMed Central

Roloff, Eva v. L.; Tomiak‐Baquero, Ana M.; Kasparov, Sergey

2016-01-01

Abstract This review aims to summarise the contemporary evidence for the presence and function of the parasympathetic innervation of the cerebral circulation with emphasis on the vertebral and basilar arteries (the posterior cerebral circulation). We consider whether the parasympathetic innervation of blood vessels could be used as a means to increase cerebral blood flow. This may have clinical implications for pathologies associated with cerebral hypoperfusion such as stroke, dementia and hypertension. Relative to the anterior cerebral circulation little is known of the origins and neurochemical phenotypes of the parasympathetic innervation of the vertebrobasilar arteries. These vessels normally provide blood flow to the brainstem and cerebellum but can, via the Circle of Willis upon stenosis of the internal carotid arteries, supply blood to the anterior cerebral circulation too. We review the multiple types of parasympathetic fibres and their distinct transmitter mechanisms and how these vary with age, disease and species. We highlight the importance of parasympathetic fibres for mediating the vasodilatory response to sympathetic activation. Current trials are investigating the possibility of electrically stimulating the postganglionic parasympathetic ganglia to improve cerebal blood flow to reduce the penumbra following stroke. We conclude that although there are substantial gaps in our understanding of the origins of parasympathetic innervation of the vertebrobasilar arteries, activation of this system under some conditions might bring therapeutic benefits. PMID:27357059

Distribution and innervation of putative peripheral arterial chemoreceptors in the red-eared slider (Trachemys scripta elegans).

PubMed

Reyes, Catalina; Fong, Angelina Y; Milsom, William K

2015-06-15

Peripheral arterial chemoreceptors have been isolated to the common carotid artery, aorta, and pulmonary artery of turtles. However, the putative neurotransmitters associated with these chemoreceptors have not yet been described. The goal of the present study was to determine the neurochemical content, innervations, and distribution of putative oxygen-sensing cells in the central vasculature of turtles and to derive homologies with peripheral arterial chemoreceptors of other vertebrates. We used tract tracing together with immunohistochemical markers for cholinergic cells (vesicular acetylcholine transporter [VAChT]), tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis), and serotonin (5HT) to identify putative oxygen-sensing cells and to determine their anatomical relation to branches of the vagus nerve (Xth cranial nerve). We found potential oxygen-sensing cells in all three chemosensory areas innervated by branches of the Xth cranial nerve. Cells containing either 5HT or VAChT were found in all three sites. The morphology and size of these cells resemble glomus cells found in amphibians, mammals, tortoises, and lizards. Furthermore, we found populations of cholinergic cells located at the base of the aorta and pulmonary artery that are likely involved in efferent regulation of vessel resistance. Catecholamine-containing cells were not found in any of the putative chemosensitive areas. The presence of 5HT- and VAChT-immunoreactive cells in segments of the common carotid artery, aorta, and pulmonary artery appears to reflect a transition between cells containing the major neurotransmitters seen in fish (5HT) and mammals (ACh and adenosine). © 2015 Wiley Periodicals, Inc.

Can surface electromyography improve surgery planning? Electromyographic assessment and intraoperative verification of the nerve bundle entry point location of the gracilis muscle.

PubMed

Romaniszyn, Michal; Walega, Piotr; Nowakowski, Michal; Nowak, Wojciech

2016-06-01

To verify the precision of surface electromyography (sEMG) in locating the innervation zone of the gracilis muscle, by comparing the location of the IZ estimated by means of sEMG with in vivo location of the nerve bundle entry point in patients before graciloplasty procedure due to fecal incontinence. Nine patients who qualified for the graciloplasty procedure underwent sEMG on both gracilis muscle before their operations. During surgery the nerve bundle was identified by means of electrical stimulation. The distance between the proximal attachment and the nerve entry point into the muscle's body was measured. Both measurements (sEMG and in vivo identification) were compared for each subject. On average, the IZ was located 65.5mm from the proximal attachment. The mean difference in location of the innervation zones in each individual was 10±9.7mm, maximal - 30mm, the difference being statistically significant (p=0.017). It was intraoperatively confirmed, that the nerve entered the muscle an average of 62mm from the proximal attachment. The largest difference between the EMG IZ estimation and nerve bundle entry point was 5mm (mean difference 2.8mm, p=0.767). Preoperative surface electromyography of both gracilis muscles is a safe, precise and reliable method of assessing the location of the innervation zones of the gracilis muscles. The asymmetry of the IZ location in left and right muscles may be important in context of technical aspects of the graciloplasty procedure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

NASA Technical Reports Server (NTRS)

Fritzsch, B.; Signore, M.; Simeone, A.

2001-01-01

We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

Afferents to the Orexin Neurons of the Rat Brain

PubMed Central

YOSHIDA, KYOKO; McCORMACK, SARAH; ESPAÑA, RODRIGO A.; CROCKER, AMANDA; SCAMMELL, THOMAS E.

2008-01-01

Emotions, stress, hunger, and circadian rhythms all promote wakefulness and behavioral arousal. Little is known about the pathways mediating these influences, but the orexin-producing neurons of the hypothalamus may play an essential role. These cells heavily innervate many wake-promoting brain regions, and mice lacking the orexin neurons have narcolepsy and fail to rouse in response to hunger (Yamanaka et al. [2003] Neuron 38:701–713). To identify the afferents to the orexin neurons, we first injected a retrograde tracer into the orexin neuron field of rats. Retrogradely labeled neurons were abundant in the allocortex, claustrum, lateral septum, bed nucleus of the stria terminalis, and in many hypothalamic regions including the preoptic area, dorsomedial nucleus, lateral hypothalamus, and posterior hypothalamus. Retrograde labeling in the brainstem was generally more modest, but labeling was strong in the periaqueductal gray matter, dorsal raphe nucleus, and lateral parabrachial nucleus. Injection of an anterograde tracer confirmed that most of these regions directly innervate the orexin neurons, with some of the heaviest input coming from the lateral septum, preoptic area, and posterior hypothalamus. In addition, hypothalamic regions preferentially innervate orexin neurons in the medial and perifornical parts of the field, but most projections from the brainstem target the lateral part of the field. Inputs from the suprachiasmatic nucleus are mainly relayed via the subparaventricular zone and dorsomedial nucleus. These observations suggest that the orexin neurons may integrate a variety of interoceptive and homeostatic signals to increase behavioral arousal in response to hunger, stress, circadian signals, and autonomic challenges. PMID:16374809

Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system

PubMed Central

Schubert, Frank K.; Hagedorn, Nicolas; Yoshii, Taishi; Helfrich‐Förster, Charlotte

2018-01-01

Abstract Drosophila melanogaster is a long‐standing model organism in the circadian clock research. A major advantage is the relative small number of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor‐labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s‐LNv) and one ITP positive dorsolateral neuron (LNd). These two clock neurons share the same spatial and functional properties. We found both neurons innervating the same brain areas with similar pre‐ and postsynaptic sites in the brain. Here the anatomical findings support their shared function as a main evening oscillator in the clock network like also found in previous studies. A second quite surprising finding addresses the large lateral ventral PDF‐neurons (l‐LNvs). We could show that the four hardly distinguishable l‐LNvs consist of two subgroups with different innervation patterns. While three of the neurons reflect the well‐known branching pattern reproduced by PDF immunohistochemistry, one neuron per brain hemisphere has a distinguished innervation profile and is restricted only to the proximal part of the medulla‐surface. We named this neuron “extra” l‐LNv (l‐LNvx). We suggest the anatomical findings reflect different functional properties of the two l‐LNv subgroups. PMID:29424420

Circuits that Innervate Excitatory-Inhibitory Cells in the Inferior Colliculus Obtained with In-Vivo Whole Cell Recordings

PubMed Central

Li, Na; Pollak, George D.

2013-01-01

Neurons excited by stimulation of one ear and suppressed by the other, called EI neurons, are sensitive to interaural intensity disparities (IIDs), the cues animals use to localize high frequencies. EI neurons are first formed in lateral superior olive (LSO), which then sends excitatory projections to the dorsal nucleus of the lateral lemniscus (DNLL) and the inferior colliculus (IC), both of which contain large populations of EI cells. We evaluate the inputs that innervate EI cells in the IC of Mexican free-tailed bats, Tadarida brasilensis mexicana, with in vivo whole cell recordings from which we derived excitatory and inhibitory conductances. We show that the basic EI property in the majority of IC cells is inherited from LSO, but each type of EI cell is also innervated by the ipsi- or contralateral DNLL, as well as additional excitatory and inhibitory inputs from monaural nuclei. We identify three EI types, where each type receives a set of projections that are different from the other types. To evaluate the role that the various projections played in generating binaural responses, we used modeling to compute a predicted response from the conductances. We then omitted one of the conductances from the computation to evaluate the degree to which that input contributed to the binaural response. We show that formation of the EI property in the various types is complex, and that some projections exert such subtle influences that they could not have been detected with extracellular recordings or even from intracellular recordings of post-synaptic potentials. PMID:23575835

Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.

PubMed

Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia; Fanti, Stefano; Sambuceti, Gianmario

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT. Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. This work might contribute to identify imaging parameters that could predict the response to CRT therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Responses to magnetic stimuli recorded in peripheral nerves in the marine nudibranch mollusk Tritonia diomedea.

PubMed

Pavlova, Galina A; Glantz, Raymon M; Dennis Willows, A O

2011-10-01

Prior behavioral and neurophysiological studies provide evidence that the nudibranch mollusk Tritonia orients to the earth's magnetic field. Earlier studies of electrophysiological responses in certain neurons of the brain to changing ambient magnetic fields suggest that although certain identified brain cells fire impulses when the ambient field is changed, these neuron somata and their central dentritic and axonal processes are themselves not primary magnetic receptors. Here, using semi-intact animal preparations from which the brain was removed, we recorded from peripheral nerve trunks. Using techniques to count spikes in individual nerves and separately also to identify, then count individual axonal spikes in extracellular records, we found both excitatory and inhibitory axonal responses elicited by changes in the direction of ambient earth strength magnetic fields. We found responses in nerves from many locations throughout the body and in axons innervating the body wall and rhinophores. Our results indicate that primary receptors for geomagnetism in Tritonia are not focally concentrated in any particular organ, but appear to be widely dispersed in the peripheral body tissues.

Can the Nerve Growth Factor promote the reinnervation of the transplanted heart?

PubMed

Galli, Alessio

2014-02-01

The activity of the heart is widely regulated by the autonomous nervous system. This important mechanism of control may be impaired in chronic diseases such as heart failure or lost in those patients who undergo heart transplantation, owing to the surgical interruption of cardiac nerves in the transplanted heart. It has been demonstrated that spontaneous reinnervation can occur in transplanted hearts and is associated with an improvement in cardiac function. However, this process may require many years and the restoration of a proper cardiac innervation and functioning during exercise is never complete. In this perspective, the Nerve Growth Factor (NGF) and other neurotrophic hormones might ameliorate cardiac innervation in the transplanted heart and should be tried in animal models. Endothelial cells engineered with a viral vector to overexpress the NGF might be engrafted in the heart and integrate into cardiac small vessels, thus providing a source of neurotrophic factors which might promote and direct regrowth and axonal sprouting of cardiac nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. I. Effects upon amino acid uptake and incorporation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, M.R.; Edwards, J.S.

1982-11-01

Chronic cercal deafferentation of the terminal ganglion in developing crickets (Acheta domesticus), which is known to suppress normal development of giant interneuron dendritic arborizations is shown here to reduce (/sup 3/H)leucine uptake and incorporation into ganglion proteins. Short term deafferentation of adult crickets, in contrast, does not depress amino acid uptake and incorporation significantly. Following unilateral long term deafferentation of the terminal ganglion, a comparison was made of the (/sup 3/H)leucine incorporation into primary dendritic processes and somata of deafferented and normally innervated medial giant interneurons (MGIs) within the same ganglion by means of quantitative autoradiography. Grain densities within dendritesmore » of deafferented MGIs were significantly lower than in paired control MGIs' grain densities within somata of deafferented MGIs also were reduced, although the effects of deafferentation were less pronounced in somata than in target dendrites. These results imply a specific influence of afferent innervation on protein metabolism during growth and development of target postsynaptic elements.« less

Correlation between muscle structure and filter characteristics of the muscle-joint system in three orthopteran insect species

PubMed

BÄSsler; BÜSchges; Meditz; BÄSsler

1996-01-01

In orthopteran insects, neural networks for joint control exhibit different characteristics due to behavioural specializations. We investigated whether these differences are generated purely by the neuronal networks, or whether characteristics of the muscles or joint architecture (muscle­joint system) are also involved in these behavioural specializations. We compared the properties of the muscle system moving the femur­tibia joint of the middle and hindleg of three species, Carausius morosus, Cuniculina impigra and Locusta migratoria. Four aspects were analysed for the tibial extensor muscle: (i) the frequency-dependence of motoneuronal activity in response to sinusoidal stimulation of the femoral chordotonal organ (fCO), (ii) the muscle structure, (iii) the innervation pattern of the muscle and (iv) the histochemical properties of the muscle fibres. These aspects were compared with the filter characteristics of the open-loop femur­tibia control system and of the muscle­joint system involved. Whereas in both phasmid species (Carausius morosus and Cuniculina impigra) the motoneuronal activity steadily increases with sinusoidal stimulation of the fCO in the frequency range 0.01­5 Hz, in Locusta migratoria there is a decrease in motoneuronal activity between 0.01 and 0.3 Hz. The muscle structure is basically similar in all three species, as the number of singly innervated muscle fibres (supplied by the fast extensor tibiae motor neurone, FETi) decreases from proximal to distal. The number of triply innervated fibres supplied by the FETi, the slow extensor tibiae (SETi) and the common inhibitor 1 (CI1) is maximal in the middle of the muscle, and the number of dually innervated fibres (supplied by SETi, CI1) increases from proximal to distal. Differences between the locust and the two phasmid species exist in the distal portion of the muscle. The phasmid extensor tibiae muscle contains a morphologically distinct bundle of muscle fibres, not present in the locust, which is mostly dually innervated and which is larger in Cuniculina impigra. Similar results were obtained for the histochemical characterisation of the muscle fibres as revealed from their staining for myofibrillar ATPase activity. The number of histochemically identified fast fibres decreased from proximal to distal, while the number of slow fibres increased. In Carausius morosus and Locusta migratoria, the percentage of slow fibres increased by up to 60­70 % at the distal end, while this increase was to almost 100 % in Cuniculina impigra. Apparently, the larger this distal region and the higher the percentage of slow, dually innervated fibres in it, the lower is the upper corner frequency (the stimulus frequency at which the joint control system produces a movement with 70 % of its maximal response amplitude) of the muscle­joint system. In summary, it appears that the upper corner frequency of the open-loop system in Locusta migratoria (<0.05 Hz) results at least in part from properties of the neuronal joint control network, but in Carausius morosus (0.5­1.0 Hz) and Cuniculina impigra (0.1­0.2 Hz) it results from the upper corner frequency of the muscle­joint system.

The density of parasympathetic axons is reduced in the exocrine pancreas of individuals recently diagnosed with type 1 diabetes.

PubMed

Lundberg, Marcus; Lindqvist, Andreas; Wierup, Nils; Krogvold, Lars; Dahl-Jørgensen, Knut; Skog, Oskar

2017-01-01

To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes. Density of parasympathetic axons was assessed by immunofluorescence and morphometry. Our main finding was a reduced density of parasympathetic axons in the exocrine, but not endocrine compartment of the pancreas in individuals with recent onset type 1 diabetes. The reduced density of parasympathetic axons in the exocrine compartment could have functional implications, e.g. be related to the exocrine insufficiency reported in type 1 diabetes patients. Further studies are needed to understand whether reduced parasympathetic innervation is a cause or consequence of type 1 diabetes.

In vitro 3D corneal tissue model with epithelium, stroma, and innervation.

PubMed

Wang, Siran; Ghezzi, Chiara E; Gomes, Rachel; Pollard, Rachel E; Funderburgh, James L; Kaplan, David L

2017-01-01

The interactions between corneal nerve, epithelium, and stroma are essential for maintaining a healthy cornea. Thus, corneal tissue models that more fully mimic the anatomy, mechanical properties and cellular components of corneal tissue would provide useful systems to study cellular interactions, corneal diseases and provide options for improved drug screening. Here a corneal tissue model was constructed to include the stroma, epithelium, and innervation. Thin silk protein film stacks served as the scaffolding to support the corneal epithelial and stromal layers, while a surrounding silk porous sponge supported neuronal growth. The neurons innervated the stromal and epithelial layers and improved function and viability of the tissues. An air-liquid interface environment of the corneal tissue was also mimicked in vitro, resulting in a positive impact on epithelial maturity. The inclusion of three cell types in co-culture at an air-liquid interface provides an important advance for the field of in vitro corneal tissue engineering, to permit improvements in the study of innervation and corneal tissue development, corneal disease, and tissue responses to environmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuropeptide Y in the adult and fetal human pineal gland.

PubMed

Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

Neuropeptide Y in the Adult and Fetal Human Pineal Gland

PubMed Central

Møller, Morten; Phansuwan-Pujito, Pansiri

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally. PMID:24757681

Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults

PubMed Central

Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P.; Nicklas, Barbara

2016-01-01

Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults. PMID:26447161

Acetylcholine receptor distribution and synapse elimination at the developing neuromuscular junction of mdx mice.

PubMed

Minatel, Elaine; Neto, Humberto Santo; Marques, Maria Julia

2003-11-01

The pattern of innervation of the vertebrate neuromuscular junction is established during early development, when junctions go from multiple to single innervation in the phenomenon of synapse elimination, suggesting that changes at the molecular level in the postsynaptic cell lead to the removal of nerve terminals. The mdx mouse is deficient in dystrophin and associated proteins that are part of the postsynaptic cytoskeleton. We used rhodamine-alpha-bungarotoxin and anti-neurofilament IgG-FITC to stain acetylcholine receptors and nerve terminals of the sternomastoid muscle during postnatal development in mdx and control C57BL/10 mice. Using fluorescence confocal microscopy, we observed that, 7 days after birth, 86.7% of the endplates of mdx mice were monoinnervated (n = 200) compared with 41.4% in control mice (n = 200). By the end of the second postnatal week, all endplates were innervated singly (100% mdx and 94.7% controls, n = 200 per group). These results show that dystrophic fibers achieve single innervation earlier, perhaps because dystrophin or a normal cytoskeletal complex is implicated in this phenomenon.

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

PubMed Central

Ashton, Jesse L.; Burton, Rebecca A. B.; Bub, Gil; Smaill, Bruce H.; Montgomery, Johanna M.

2018-01-01

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation. PMID:29615932

The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

PubMed

Chartier, Stephane R; Mitchell, Stefanie A T; Majuta, Lisa A; Mantyh, Patrick W

2018-02-10

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle.

PubMed Central

O'Brien, R A; Ostberg, A J; Vrbová, G

1978-01-01

1. The mechanism responsible for the elimination of polyneuronal innervation in developing rat soleus muscles was studied electrophysiologically and histologically. 2. Initially all the axons contacting a single end-plate have simple bulbous terminals. As elimination proceeds one axon develops terminal branches while the other terminals remain bulbous and may be seen in contact with, or a short distance away from, the end-plate. It is suggested that the branched terminal remains in contact with the muscle fibre while the other terminals withdraw. 3. At a time when polyneuronal innervation can no longer be detected electrophysiologically, the histological technique still shows the presence of end-plates contacted by more than one nerve terminal. 4. The effect of activity on the disappearance of polyneuronal innervation was examined. Activity was increased by electrical stimulation of the right sciatic nerve. This procedure also produced reflex activity in the contralateral limb. In both cases polyneuronal innervation was eliminated more rapidly in the active muscles. 5. The finding that proteolytic enzymes are released from muscles treated with acetylcholine (ACh), and the observation of the more rapid elimination of supernumerary terminals at the end-plates of active muscles, lead to the suggestion that superfluous nerve-muscle contacts are removed by the proteolytic enzymes in response to neuromuscular activity. The selective stabilization of only one of the terminals is discussed in the light of these results. Images Plate 1 Plate 2 PMID:722562

Compartmental Innervation of the Superior Oblique Muscle in Mammals.

PubMed

Le, Alan; Poukens, Vadims; Ying, Howard; Rootman, Daniel; Goldberg, Robert A; Demer, Joseph L

2015-10-01

Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action.

Phosphorylation of p38 in Trigeminal Ganglion Neurons Contributes to Tongue Heat Hypersensitivity in Mice.

PubMed

Maruno, Mitsuru; Shinoda, Masamichi; Honda, Kuniya; Ito, Reio; Urata, Kentaro; Watanabe, Masahiro; Okada, Shinji; Lee, Jun; Gionhaku, Nobuhito; Iwata, Koichi

2017-01-01

To develop a tongue pain model with no mucosal pathologic changes and to examine whether phosphorylation of p38 in trigeminal ganglion (TG) neurons innervating the tongue is associated with tongue heat hypersensitivity in mice. Tongue heat sensitivity in mice was assessed following application of the irritant 2,4,6-trinitrobenzene sulfonic acid (TNBS) to the tongue. After TNBS application, the expressions of p38, phosphorylated p38 (pp38), and transient receptor potential vanilloid 1 (TRPV1) were examined in TG neurons innervating the tongue. To further assess changes in tongue heat sensitivity and TRPV1 expression, a specific inhibitor of p38 phosphorylation (SB203580) was also administered into the TG. Student t test or two-way repeated-measures analysis of variance followed by Sidak multiple comparison test were used for statistical analysis, and P < .05 was considered statistically significant. TNBS application to the tongue induced noninflammatory heat hypersensitivity accompanied by the enhancement of p38 phosphorylation in TG neurons innervating the tongue and by an increase in the number of TRPV1 and pp38-immunoreactive (IR) TG neurons innervating the tongue. Intra-TG administration of SB203580 suppressed the increase in the TRPV1 and pp38-IR TG neurons and alleviated the noninflammatory tongue heat hypersensitivity induced by TNBS. p38 signaling cascades are involved in tongue heat hyperalgesia in association with TRPV1 upregulation in TG neurons innervating the TNBS-treated tongue.

Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity

PubMed Central

Brauer, M. Mónica; Smith, Peter G.

2014-01-01

The female reproductive tract undergoes remarkable functional and structural changes associated with cycling, conception and pregnancy, and it is likely advantageous to both individual and species to alter relationships between reproductive tissues and innervation. For several decades, it has been appreciated that the mammalian uterus undergoes massive sympathetic axon depletion in late pregnancy, possibly representing an adaptation to promote smooth muscle quiescence and sustained blood flow. Innervation to other structures such as cervix and vagina also undergo pregnancy-related changes in innervation that may facilitate parturition. These tissues provide highly tractable models for examining cellular and molecular mechanisms underlying peripheral nervous system plasticity. Studies show that estrogen elicits rapid degeneration of sympathetic terminal axons in myometrium, which regenerate under low-estrogen conditions. Degeneration is mediated by the target tissue: under estrogen's influence, the myometrium produces proteins repulsive to sympathetic axons including BDNF, neurotrimin, semaphorins, and pro-NGF, and extracellular matrix components are remodeled. Interestingly, nerve depletion does not involve diminished levels of classical sympathetic neurotrophins that promote axon growth. Estrogen also affects sympathetic neuron neurotrophin receptor expression in ways that appear to favor pro-degenerative effects of the target tissue. In contrast to the uterus, estrogen depletes vaginal autonomic and nociceptive axons, with the latter driven in part by estrogen-induced suppression BMP4 synthesis. These findings illustrate that hormonally mediated physiological plasticity is a highly complex phenomenon involving multiple, predominantly repulsive target-derived factors acting in concert to achieve rapid and selective reductions in innervation. PMID:25530517

Gray Matter NG2 Cells Display Multiple Ca2+-Signaling Pathways and Highly Motile Processes

PubMed Central

Haseleu, Julia; Pohle, Jörg; Karram, Khalad; Trotter, Jacqueline; Seifert, Gerald; Frotscher, Michael; Steinhäuser, Christian; Jabs, Ronald

2011-01-01

NG2 cells, the fourth type of glia in the mammalian CNS, receive synaptic input from neurons. The function of this innervation is unknown yet. Postsynaptic changes in intracellular Ca2+-concentration ([Ca2+]i) might be a possible consequence. We employed transgenic mice with fluorescently labeled NG2 cells to address this issue. To identify Ca2+-signaling pathways we combined patch-clamp recordings, Ca2+-imaging, mRNA-transcript analysis and focal pressure-application of various substances to identified NG2-cells in acute hippocampal slices. We show that activation of voltage-gated Ca2+-channels, Ca2+-permeable AMPA-receptors, and group I metabotropic glutamate-receptors provoke [Ca2+]i-elevations in NG2 cells. The Ca2+-influx is amplified by Ca2+-induced Ca2+-release. Minimal electrical stimulation of presynaptic neurons caused postsynaptic currents but no somatic [Ca2+]i elevations, suggesting that [Ca2+]i elevations in NG2 cells might be restricted to their processes. Local Ca2+-signaling might provoke transmitter release or changes in cell motility. To identify structural prerequisites for such a scenario, we used electron microscopy, immunostaining, mRNA-transcript analysis, and time lapse imaging. We found that NG2 cells form symmetric and asymmetric synapses with presynaptic neurons and show immunoreactivity for vesicular glutamate transporter 1. The processes are actin-based, contain ezrin but not glial filaments, microtubules or endoplasmic reticulum. Furthermore, we demonstrate that NG2 cell processes in situ are highly motile. Our findings demonstrate that gray matter NG2 cells are endowed with the cellular machinery for two-way communication with neighboring cells. PMID:21455301

Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

PubMed

Seifert, P; Spitznas, M

1999-06-01

This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

PubMed Central

Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

2016-01-01

Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

Functional reconstruction of total lower lip defects using innervated gracilis flap in the setting of high-energy ballistic injury to the lower face: preliminary report.

PubMed

Gurunluoglu, Raffi; Glasgow, Mark; Williams, Susan A; Gurunluoglu, Aslin; Antrobus, Jarod; Eusterman, Vincent

2012-10-01

Reconstruction of total full-thickness lower lip defects combined with extensive composite mandibular defects particularly in the setting of close-range high-energy ballistic injury presents a formidable challenge for the reconstructive plastic surgeon. While the fibular flap has been widely accepted for its usefulness in the reconstruction of composite mandibular defects, to date, there is no definitive widely established method of total lower lip reconstruction. The article presents authors' approach using innervated gracilis muscle flap for total lower lip reconstruction in the setting of high-energy gunshot injuries to the face. Three patients underwent composite mandibular defect reconstruction using fibular osteocutaneous flap and functional lower lip reconstruction using innervated gracilis muscle flap. Lip lining was reconstructed using the skin paddle of the fibular flap. The external surface of the gracilis muscle was skin-grafted. Facial artery myomucosal flap provided vermilion reconstruction in two patients. All fibular (n=3) and gracilis flap transfers (n=3) were viable. An electromyographic study at 1 year postoperatively demonstrated successful re-innervation of the gracilis muscle. Starting at about 10 weeks postoperatively, patients exhibited voluntary lip movements and oral competence. In addition, all patients achieved near-normal speech, evidence of recovered protective sensitivity and satisfactory appearance. The mean follow-up was 16.1 months. Our preliminary report in three patients demonstrated that innervated gracilis muscle transfer combined with fibular flap provides a successful reconstruction of extensive composite mandibular and total lower lip defects resulting from gunshot injuries to the face. Oral continence was achieved by combination of regained tonicity and voluntary movement of the gracilis muscle following re-innervation and assistance of the cheek muscles on the gracilis muscle. The described technique was reliable and the results were promising. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Effects of surgical lesions on choline acetyltransferase activity in the cat cochlea.

PubMed

Frilling, Mark J; Wiet, Gregory J; Godfrey, Donald A; Parli, Judy A; Dunn, Jon D; Ross, C David

2017-12-01

Although it is well established that the choline acetyltransferase (ChAT, the enzyme for acetylcholine synthesis) in the mammalian cochlea is associated with its olivocochlear innervation, the distribution of this innervation in the cochlea varies somewhat among mammalian species. The quantitative distribution of ChAT activity in the cochlea has been reported for guinea pigs and rats. The present study reports the distribution of ChAT activity within the organ of Corti among the three turns of the cat cochlea and the effects of removing olivocochlear innervation either by a lateral cut aimed to totally transect the left olivocochlear bundle or a more medial cut additionally damaging the superior olivary complex on the same side. Similarly to results for guinea pig and rat, the distribution of ChAT activity in the cat outer hair cell region showed a decrease from base to apex, but, unlike in the guinea pig and rat, the cat inner hair cell region did not. As in the rat, little ChAT activity was measured in the outer supporting cell region. As previously reported for whole cat cochlea and for rat cochlear regions, transection of the olivocochlear bundle resulted in almost total loss of ChAT activity in the hair cell regions of the cat cochlea. Lesions of the superior olivary complex resulted in loss of ChAT activity in the inner hair cell region of all cochlear turns only on the lesion side but bilateral losses in the outer hair cell region of all turns. The results are consistent with previous evidence that virtually all cholinergic synapses in the mammalian cochlea are associated with its olivocochlear innervation, that the olivocochlear innervation to the inner hair cell region is predominantly ipsilateral, and that the olivocochlear innervation to the outer hair cells is bilateral. Copyright © 2017 Elsevier B.V. All rights reserved.

Somatotopy in the Medullary Dorsal Horn As a Basis for Orofacial Reflex Behavior

PubMed Central

Panneton, W. Michael; Pan, BingBing; Gan, Qi

2017-01-01

The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I–V. Projections to lamina II exhibited the most focused somatotopy when individual cases were compared. Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus resulted in labeled neurons almost solely in lamina V of the trigeminocervical complex. The distribution of these labeled neurons paralleled the somatotopy of primary afferent fibers, e.g., those labeled after FG injections into a functional group of motoneurons innervating lip musculature were found most rostrally while those labeled after injections into motoneurons innervating snout, periocular and preauricular muscles, respectively, were found at progressively more caudal levels. Anterograde transport of injections of biotinylated dextran amine into lamina V at different rostrocaudal levels of the trigeminocervical complex confirmed the notion that the somatotopy of orofacial sensory fields parallels the musculotopy of facial motor neurons. These data suggest that neurons in lamina V are important interneurons in a simple orofacial reflex circuit consisting of a sensory neuron, interneuron and motor neuron. Moreover, the somatotopy of primary afferent fibers from the head and neck confirms the “onion skin hypothesis” and suggests rostral cervical dermatomes blend seamlessly with “cranial dermatomes.” The transition area between subnucleus interpolaris and subnucleus caudalis is addressed while the paratrigeminal nucleus is discussed as an interface between the somatic and visceral nervous systems. PMID:29066998

Expression of TRPV1 channels by Cajal-Retzius cells and layer-specific modulation of synaptic transmission by capsaicin in the mouse hippocampus.

PubMed

Anstötz, Max; Lee, Sun Kyong; Maccaferri, Gianmaria

2018-05-28

By taking advantage of calcium imaging and electrophysiology, we provide direct pharmacological evidence for the functional expression of TRPV1 channels in hippocampal Cajal-Retzius cells. Application of the TRPV1 activator capsaicin powerfully enhances spontaneous synaptic transmission in the hippocampal layers that are innervated by the axons of Cajal-Retzius cells. Capsaicin-triggered calcium responses and membrane currents in Cajal-Retzius cells, as well as layer-specific modulation of spontaneous synaptic transmission, are absent when the drug is applied to slices prepared from TRPV1 - / - animals. We discuss the implications of the functional expression of TRPV1 channels in Cajal-Retzius cells and of the observed TRPV1-dependent layer-specific modulation of synaptic transmission for physiological and pathological network processing. The vanilloid receptor TRPV1 forms complex polymodal channels that are expressed by sensory neurons and play a critical role in nociception. Their distribution pattern and functions in cortical circuits are, however, much less understood. Although TRPV1 reporter mice have suggested that, in the hippocampus, TRPV1 is predominantly expressed by Cajal-Retzius cells (CRs), direct functional evidence is missing. As CRs powerfully excite GABAergic interneurons of the molecular layers, TRPV1 could play important roles in the regulation of layer-specific processing. Here, we have taken advantage of calcium imaging with the genetically encoded indicator GCaMP6s and patch-clamp techniques to study the responses of hippocampal CRs to the activation of TRPV1 by capsaicin, and have compared the effect of TRPV1 stimulation on synaptic transmission in layers innervated or non-innervated by CRs. Capsaicin induced both calcium responses and membrane currents in ∼50% of the cell tested. Neither increases of intracellular calcium nor whole-cell currents were observed in the presence of the TRPV1 antagonists capsazepine/Ruthenium Red or in slices prepared from TRPV1 knockout mice. We also report a powerful TRPV1-dependent enhancement of spontaneous synaptic transmission onto interneurons with dendritic trees confined to the layers innervated by CRs. In conclusion, our work establishes that functional TRPV1 is expressed by a significant fraction of CRs and we propose that TRPV1 activity may regulate layer-specific synaptic transmission in the hippocampus. Lastly, as CR density decreases during postnatal development, we also propose that functional TRPV1 receptors may be related to mechanisms involved in CR progressive reduction by calcium-dependent toxicity/apoptosis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Distribution of vesicular glutamate transporter 1 (VGLUT1) in the mouse esophagus.

PubMed

Kraus, T; Neuhuber, W L; Raab, M

2007-08-01

In rat and mouse esophagus, vesicular glutamate transporter 2 (VGLUT2) has been demonstrated to identify vagal intraganglionic laminar endings (IGLEs); this has recently also been shown for VGLUT1 in rat esophagus. In this study, we have investigated the distribution of VGLUT1 in the mouse esophagus and compared these results with the recently published data from the rat esophagus. Unexpectedly, we have discovered that VGLUT1 mostly fails to identify IGLEs in the mouse esophagus. This is surprising, since the distribution of VGLUT2 shows comparable results in both species. Confocal imaging has revealed substantial colocalization of VGLUT1 immunoreactivity (-ir) with cholinergic and nitrergic/peptidergic markers within the myenteric neuropil and in both cholinergic and nitrergic myenteric neuronal cell bodies. VGLUT1 and cholinergic markers have also been colocalized in fibers of the muscularis mucosae, whereas VGLUT1 and nitrergic markers have never been colocalized in fibers of the muscularis mucosae, although this does occur in fibers of the muscularis running to motor endplates. Thus, VGLUT1 is contained in the nitrergic innervation of mouse esophageal motor endplates, another difference from the rat esophagus. VGLUT1-ir is therefore present in extrinsic and intrinsic innervation of the mouse esophagus, but the significant differences from the rat indicate species variations concerning the distribution of VGLUTs in the peripheral nervous system.

Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro

PubMed Central

Maccaferri, Gianmaria; David, J; Roberts, B; Szucs, Peter; Cottingham, Carol A; Somogyi, Peter

2000-01-01

Inhibitory postsynaptic currents (IPSCs) evoked in CA1 pyramidal cells (n = 46) by identified interneurones (n = 43) located in str. oriens were recorded in order to compare their functional properties and to determine the effect of synapse location on the apparent IPSC kinetics as recorded using somatic voltage clamp at −70 mV and nearly symmetrical [Cl−]. Five types of visualised presynaptic interneurone, oriens-lacunosum moleculare (O-LMC), basket (BC), axo-axonic (AAC), bistratified (BiC) and oriens-bistratified (O-BiC) cells, were distinguished by immunocytochemistry and/or synapse location using light and electron microscopy. Somatostatin immunoreactive O-LMCs, innervating the most distal dendritic shafts and spines, evoked the smallest amplitude (26 ± 10 pA, s.e.m., n = 8) and slowest IPSCs (10–90 % rise time, 6.2 ± 0.6 ms; decay, 20.8 ± 1.7 ms, n = 8), with no paired-pulse modulation of the second IPSC (93 ± 4 %) at 100 ms interspike interval. In contrast, parvalbumin-positive AACs evoked larger amplitude (308 ± 103 pA, n = 7) and kinetically faster (rise time, 0.8 ± 0.1 ms; decay 11.2 ± 0.9 ms, n = 7) IPSCs showing paired-pulse depression (to 68 ± 5 %, n = 6). Parvalbumin- or CCK-positive BCs (n = 9) terminating on soma/dendrites, BiCs (n = 4) and O-BiCs (n = 7) innervating dendrites evoked IPSCs with intermediate kinetic parameters. The properties of IPSCs and sensitivity to bicuculline indicated that they were mediated by GABAA receptors. In three cases, kinetically complex, multiphasic IPSCs, evoked by an action potential in the recorded basket cells, suggested that coupled interneurones, possibly through electrotonic junctions, converged on the same postsynaptic neurone. The population of O-BiCs (4 of 4 somatostatin positive) characterised in this study had horizontal dendrites restricted to str. oriens/alveus and innervated stratum radiatum and oriens. Other BiCs had radial dendrites as described earlier. The parameters of IPSCs evoked by BiCs and O-BiCs showed the largest cell to cell variation, and a single interneurone could evoke both small and slow as well as large and relatively fast IPSCs. The kinetic properties of the somatically recorded postsynaptic current are correlated with the innervated cell surface domain. A significant correlation of rise and decay times for the overall population of unitary IPSCs suggests that electrotonic filtering of distal responses is a major factor for the location and cell type specific differences of unitary IPSCs, but molecular heterogeneity of postsynaptic GABAA receptors may also contribute to the observed kinetic differences. Furthermore, domain specific differences in the short-term plasticity of the postsynaptic response indicate a differentiation of interneurones in activity-dependent responses. PMID:10747186

Plasticity of serotonergic innervation of the inferior colliculus in mice following acoustic trauma

PubMed Central

Papesh, Melissa A.; Hurley, Laura M.

2012-01-01

Acoustic trauma often results in permanent damage to the cochlea, triggering changes in processing within central auditory structures such as the inferior colliculus (IC). The serotonergic neuromodulatory system, present in the IC, is responsive to chronic changes in the activity of sensory systems. The current study investigated whether the density of serotonergic innervation in the IC is changed following acoustic trauma. The trauma stimulus consisted of an 8 kHz pure tone presented at a level of 113 dB SPL for six consecutive hours to anesthetized CBA/J mice. Following a minimum recovery period of three weeks, serotonergic fibers were visualized via histochemical techniques targeting the serotonin reuptake transporter (SERT) and quantified using stereologic probes. SERT-positive fiber densities were then compared between the traumatized and protected hemispheres of unilaterally traumatized subjects and those of controls. A significant effect of acoustic trauma was found between the hemispheres of unilaterally traumatized subjects such that the IC contralateral to the ear of exposure contained a lower density of SERT-positive fibers than the IC ipsilateral to acoustic trauma. No significant difference in density was found between the hemispheres of control subjects. Additional dimensions of variability in serotonergic fibers were seen among subdivisions of the IC and with age. The central IC had a slightly but significantly lowered density of serotonergic fibers than other subdivisions of the IC, and serotonergic fibers also declined with age. Overall, the results indicate that acoustic trauma is capable of producing modest but significant decreases in the density of serotonergic fibers innervating the IC. PMID:22101024

Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells

PubMed Central

Miyazaki, Taisuke; Yamasaki, Miwako; Hashimoto, Kouichi; Kohda, Kazuhisa; Yuzaki, Michisuke; Shimamoto, Keiko; Tanaka, Kohichi; Kano, Masanobu; Watanabe, Masahiko

2017-01-01

Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the l-glutamate/l-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF–PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10–90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted from PC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs. PMID:28655840

Mixed input to olfactory glomeruli from two subsets of ciliated sensory neurons does not impede relay neuron specificity in the crucian carp.

PubMed

Hansson, Kenth-Arne; Døving, Kjell B; Skjeldal, Frode M

2015-10-01

The consensus view of olfactory processing is that the axons of receptor-specific primary olfactory sensory neurons (OSNs) converge to a small subset of glomeruli, thus preserving the odour identity before the olfactory information is processed in higher brain centres. In the present study, we show that two different subsets of ciliated OSNs with different odorant specificities converge to the same glomeruli. In order to stain different ciliated OSNs in the crucian carp Carassius carassius we used two different chemical odorants, a bile salt and a purported alarm substance, together with fluorescent dextrans. The dye is transported within the axons and stains glomeruli in the olfactory bulb. Interestingly, the axons from the ciliated OSNs co-converge to the same glomeruli. Despite intermingled innervation of glomeruli, axons and terminal fields from the two different subsets of ciliated OSNs remained mono-coloured. By 4-6 days after staining, the dye was transported trans-synaptically to separately stained axons of relay neurons. These findings demonstrate that specificity of the primary neurons is retained in the olfactory pathways despite mixed innervation of the olfactory glomeruli. The results are discussed in relation to the emerging concepts about non-mammalian glomeruli. © 2015. Published by The Company of Biologists Ltd.

More a finger than a nose: the trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.

PubMed

Amey-Özel, Monique; von der Emde, Gerhard; Engelmann, Jacob; Grant, Kirsty

2015-04-01

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied. © 2014 Wiley Periodicals, Inc.

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons in Drosophila fertility

PubMed Central

Castellanos, Monica C.; Tang, Jonathan C. Y.; Allan, Douglas W.

2013-01-01

In Drosophila melanogaster, much of our understanding of sexually dimorphic neuronal development and function comes from the study of male behavior, leaving female behavior less well understood. Here, we identify a post-embryonic population of Insulin-like peptide 7 (Ilp7)-expressing neurons in the posterior ventral nerve cord that innervate the reproductive tracts and exhibit a female bias in their function. They form two distinct dorsal and ventral subsets in females, but only a single dorsal subset in males, signifying a rare example of a female-specific neuronal subset. Female post-embryonic Ilp7 neurons are glutamatergic motoneurons innervating the oviduct and are required for female fertility. In males, they are serotonergic/glutamatergic neuromodulatory neurons innervating the seminal vesicle but are not required for male fertility. In both sexes, these neurons express the sex-differentially spliced fruitless-P1 transcript but not doublesex. The male fruitless-P1 isoform (fruM) was necessary and sufficient for serotonin expression in the shared dorsal Ilp7 subset, but although it was necessary for eliminating female-specific Ilp7 neurons in males, it was not sufficient for their elimination in females. By contrast, sex-specific RNA-splicing by female-specific transformer is necessary for female-type Ilp7 neurons in females and is sufficient for their induction in males. Thus, the emergence of female-biased post-embryonic Ilp7 neurons is mediated in a subset-specific manner by a tra- and fru-dependent mechanism in the shared dorsal subset, and a tra-dependent, fru-independent mechanism in the female-specific subset. These studies provide an important counterpoint to studies of the development and function of male-biased neuronal dimorphism in Drosophila. PMID:23981656

Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area

PubMed Central

Lasztóczi, Bálint; Tukker, John J.; Somogyi, Peter; Klausberger, Thomas

2015-01-01

Hippocampal oscillations reflect coordinated neuronal activity on many timescales. Distinct types of GABAergic interneuron participate in the coordination of pyramidal cells over different oscillatory cycle phases. In the CA3 area, which generates sharp waves and gamma oscillations, the contribution of identified GABAergic neurons remains to be defined. We have examined the firing of a family of cholecystokinin-expressing interneurons during network oscillations in urethane-anesthetized rats and compared them with firing of CA3 pyramidal cells. The position of the terminals of individual visualized interneurons was highly diverse, selective, and often spatially coaligned with either the entorhinal or the associational inputs to area CA3. The spike timing in relation to theta and gamma oscillations and sharp waves was correlated with the innervated pyramidal cell domain. Basket and dendritic-layer-innervating interneurons receive entorhinal and associational inputs and preferentially fire on the ascending theta phase, when pyramidal cell assemblies emerge. Perforant-path-associated cells, driven by recurrent collaterals of pyramidal cells fire on theta troughs, when established pyramidal cell assemblies are most active. In the CA3 area, slow and fast gamma oscillations occurred on opposite theta oscillation phases. Perforant-path-associated and some COUP-TFII-positive interneurons are strongly coupled to both fast and slow gamma oscillations, but basket and dendritic-layer-innervating cells are weakly coupled to fast gamma oscillations only. During sharp waves, different interneuron types are activated, inhibited, or remain unaffected. We suggest that specialization in pyramidal cell domain and glutamatergic input-specific operations, reflected in the position of GABAergic terminals, is the evolutionary drive underlying the diversity of cholecystokinin-expressing interneurons. PMID:22159120

Embryonic development of the innervation of the locust extensor tibiae muscle by identified neurons: formation and elimination of inappropriate axon branches.

PubMed

Myers, C M; Whitington, P M; Ball, E E

1990-01-01

Intracellular dye fills have been used to reveal the pattern of embryonic growth of each of the four neurons which innervate the extensor tibiae muscle (ETi) of the hind leg of the locust. The growth cone of the slow extensor tibiae motoneuron (SETi), the first of the four neurons to leave the central nervous system, pioneers nerve 3 (N3). The fast extensor motoneuron (FETi), the next neuron to grow out, follows earlier outgrowing motoneurons into the periphery in nerve 5 (N5) and then rejoins SETi in N3. As it transfers from N5 to N3, it is transiently dye-coupled to the Tr1 pioneer neuron which spans the gap between the two nerves. It then follows SETi onto the ETi muscle in the femur. The common inhibitory neuron and the dorsal unpaired median neuron (DUMETi) follow SETi and FETi in nerves 3B2 and 5B1, respectively. SETi's growth cone requires almost twice as long to reach ETi as those of the three later motoneurons, all of which follow preexisting neural pathways. At least three of the four developing motoneurons form one or more axon branches not found in the adult. These branches may occur (1) at segmental boundaries; (2) where the nerve, which the growth cone is following, itself branches or the growth cone encounters another nerve; or (3) when the axon continues to grow beyond its target muscle. These findings contrast with the apparent absence of inappropriate axon branches in another developing locust neuromuscular system and during the innervation of zebrafish myotomes, but resemble in some ways the transient production of inappropriate axonal branches reported for embryonic leech motoneurons.

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

PubMed

Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

2016-04-01

To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Disorders of the autonomic nervous system in patients with Brugada syndrome: a pilot study.

PubMed

Kostopoulou, Anna; Koutelou, Maria; Theodorakis, Georgios; Theodorakos, Athanasios; Livanis, Efthimios; Maounis, Themistoklis; Chaidaroglou, Antigoni; Degiannis, Dimitrios; Voudris, Vassilis; Kremastinos, Dimitrios; Cokkinos, Dennis

2010-07-01

The aim of this study was to examine autonomic disorders in patients with Brugada syndrome by performing a cardiac sympathetic innervation evaluation, a head-up tilt-test (HUT) and heart rate variability (HRV) analysis. We enrolled 20 patients with Brugada syndrome (mean age 42.5 +/- 8.8 years), 9 with spontaneous and 11 with an induced type 1 electrocardiogram (ECG) in the setting of symptoms and 20 age-matched controls. All subjects underwent a HUT with parallel measurements of plasma catecholamines and cortisol, a (123)I-metaiodobenzylguanidine single photon emission tomography, and HRV evaluation. Ten control subjects participated in the innervation portion of the study. The tilt-test with clomipramine challenge was positive in 15 of 20 (75%) patients (7 spontaneous, 8 induced) and in 1 in controls (P < 0.01). A sympathoadrenal imbalance was shown in positive tests. The pattern of innervation in all groups was heterogenic and similar to controls with a trend towards lower measurements in patients with a spontaneous type 1 ECG and a positive HUT. HRV analysis did not reveal any significant differences during day and night. Four patients (20%) had sustained ventricular arrhythmias during a follow-up of 31.1 +/- 8.6 months, but no correlations with innervation or response to tilting were found. A high susceptibility to vasovagal syncope was observed in patients with Brugada syndrome, which could be disease-related symptoms. Conversely, sympathetic innervation was observed to follow a physiological, heterogenic pattern; however, these factors did not have prognostic value for life-threatening arrhythmias.

Efficacy of lateral- versus medial-approach hip joint capsule denervation as surgical treatments of the hip joint pain; a neuronal tract tracing study in the sheep

PubMed Central

Sienkiewicz, Waldemar; Dudek, Agnieszka; Czaja, Krzysztof; Janeczek, Maciej; Chrószcz, Aleksander; Kaleczyc, Jerzy

2018-01-01

Objective To evaluate efficacy of denervation of the of the hip joint capsule (HJC), as a treatment of hip joint pain. Specifically, we tested the hypothesis that HJC denervation will significantly reduce the number of sensory neurons innervating the capsule. Study design Denervation of the HJC from a medial or lateral approach was followed by retrograde tracing of sensory neurons innervating the capsule. Animals Twenty adult male sheep (30–40 kg of body weight; Polish merino breed) were used in the study. Methods The hip joint was denervated from medial (n = 5) or lateral (n = 5) surgical approaches. Immediately after denervation, the retrograde neural tract tracer Fast Blue (FB) was injected into the HJC. An additional ten animals (n = 5 for medial and n = 5 for lateral approach) received the same treatment without HJC denervation to provide the appropriate controls. Results Results of the study revealed that the vast majority of retrogradely labelled sensory neurons innervating the HJC originate from fifth lumbar to second sacral dorsal root ganglia. Both the medial and the lateral denervations significantly reduced the number of sensory neurons innervating the HJC (39.2% and 69.0% reduction respectively). Conclusions These results show that denervation of the HJC is an effective surgical procedure for reduction of the sensory neuronal input to the HJC. Moreover, the lateral approach was found to be significantly more effective for reducing sensory innervation as compared to the medial one. PMID:29329303

Variant BDNF-Val66Met Polymorphism is Associated with Layer-Specific Alterations in GABAergic Innervation of Pyramidal Neurons, Elevated Anxiety and Reduced Vulnerability of Adolescent Male Mice to Activity-Based Anorexia.

PubMed

Chen, Yi-Wen; Surgent, Olivia; Rana, Barkha S; Lee, Francis; Aoki, Chiye

2017-08-01

Previously, we determined that rodents' vulnerability to food restriction (FR)-evoked wheel running during adolescence (activity-based anorexia, ABA) is associated with failures to increase GABAergic innervation of hippocampal and medial prefrontal pyramidal neurons. Since brain-derived neurotrophic factor (BDNF) promotes GABAergic synaptogenesis, we hypothesized that individual differences in this vulnerability may arise from differences in the link between BDNF bioavailability and FR-evoked wheel running. We tested this hypothesis in male BDNF-Val66Met knock-in mice (BDNFMet/Met), known for reduction in the activity-dependent BDNF secretion and elevated anxiety-like behaviors. We found that 1) in the absence of FR or a wheel (i.e., control), BDNFMet/Met mice are more anxious than wild-type (WT) littermates, 2) electron microscopically verified GABAergic innervations of pyramidal neurons of BDNFMet/Met mice are reduced at distal dendrites in hippocampal CA1 and medial prefrontal cortex, 3) following ABA, WT mice exhibit anxiety equal to those of the BDNFMet/Met mice and have lost GABAergic innervation along distal dendrites, 4) BDNFMet/Met mice show blunted ABA vulnerability, and 5) unexpectedly, GABAergic innervation is higher at somata of BDNFMet/Met mice than of WT. We conclude that lamina-specific GABAergic inhibition is important for regulating anxiety, whether arising from environmental stress, such as food deprivation, or genetically, such as BDNFMet/Met single nucleotide polymorphism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sympathetic reinnervation of peripheral targets following bilateral axotomy of the adult superior cervical ganglion

PubMed Central

Hesp, Zoe C.; Zhu, Zheng; Morris, Teresa A.; Walker, Ryan G.; Isaacson, L.G.

2012-01-01

The ability of adult injured postganglionic axons to reinnervate cerebrovascular targets is unknown, yet these axons can influence cerebral blood flow, particularly during REM sleep. The objective of the present study was to assess quantitatively the sympathetic reinnervation of vascular as well as non-vascular targets following bilateral axotomy of the superior cervical ganglion (SCG) at short term (1 day, 7 days) and long term (8 weeks, 12 weeks) survival time points. The sympathetic innervation of representative extracerebral blood vessels [internal carotid artery (ICA), basilar artery (BA), middle cerebral artery (MCA)], the submandibular gland (SMG), and pineal gland was quantified following injury using an antibody to tyrosine hydroxylase (TH). Changes in TH innervation were related to TH protein content in the SCG. At 7 days following bilateral SCG axotomy, all targets were significantly depleted of TH innervation, and the exact site on the BA where SCG input was lost could be discerned. Complete sympathetic reinnervation of the ICA was observed at long term survival times, yet TH innervation of other vascular targets showed significant decreases even at 12 weeks following axotomy. The SMG was fully reinnervated by 12 weeks, yet TH innervation of the pineal gland remained significantly decreased. TH protein in the SCG was significantly decreased at both short term and long term time points and showed little evidence of recovery. Our data demonstrate a slow reinnervation of most vascular targets following axotomy of the SCG with only minimal recovery of TH protein in the SCG at 12 weeks following injury. PMID:22842079

Distribution, Innervation, and Cellular Organization of Taste Buds in the Sea Catfish, Plotosus japonicus.

PubMed

Nakamura, Tatsufumi; Matsuyama, Naoki; Kirino, Masato; Kasai, Masanori; Kiyohara, Sadao; Ikenaga, Takanori

2017-01-01

The gustatory system of the sea catfish Plotosus japonicus, like that of other catfishes, is highly developed. To clarify the details of the morphology of the peripheral gustatory system of Plotosus, we used whole-mount immunohistochemistry to investigate the distribution and innervation of the taste buds within multiple organs including the barbels, oropharyngeal cavity, fins (pectoral, dorsal, and caudal), and trunk. Labeled taste buds could be observed in all the organs examined. The density of the taste buds was higher along the leading edges of the barbels and fins; this likely increases the chance of detecting food. In all the fins, the taste buds were distributed in linear arrays parallel to the fin rays. Labeling of nerve fibers by anti-acetylated tubulin antibody showed that the taste buds within each sensory field are innervated in different ways. In the barbels, large nerve bundles run along the length of the organ, with fascicles branching off to innervate polygonally organized groups of taste buds. In the fins, nerve bundles run along the axis of fin rays to innervate taste buds lying in a line. In each case, small fascicles of fibers branch from large bundles and terminate within the basal portions of the taste buds. Serotonin immunohistochemistry demonstrated that most of the taste buds in all the organs examined contained disk-shaped serotonin-immunopositive cells in their basal region. This indicates a similar organization of the taste buds, in terms of the existence of serotonin-immunopositive basal cells, across the different sensory fields in this species. © 2017 S. Karger AG, Basel.

Evaluation of muscle hyperactivity of the grimacing muscles by unilateral tight eyelid closure and stapedius muscle tone.

PubMed

Shiba, Masato; Matsuo, Kiyoshi; Ban, Ryokuya; Nagai, Fumio

2012-10-01

Muscle hyperactivity of grimacing muscles, including the orbicularis oculi and corrugator supercilii muscles that cause crow's feet and a glabellar frown line with ageing, cannot be accurately evaluated by surface observation. In 71 subjects, this study investigated the extent to which grimacing muscles are innervated by the bilateral motor cortices, whether the corticofacial projection to the grimacing muscles affects the facially innervated stapedius muscle tone by measuring static compliance of the tympanic membrane, and whether unilateral tight eyelid closure with contraction of the grimacing muscles changes static compliance. Unilateral tight eyelid closure and its subsequent change in the contralateral vertical medial eyebrow position revealed that motor neurons of the orbicularis oculi and corrugator supercilii muscles were innervated by the bilateral motor cortices with weak-to-strong contralateral dominance. The orbicularis oculi, corrugator supercilii, and stapedius muscles innervated by the bilateral motor cortices had increased muscle hyperactivity, which lowered the vertical medial eyebrow position and decreased the static compliance of the tympanic membrane more than those innervated by the unilateral motor cortex. Unilateral enhanced tight eyelid closure with contraction of the grimacing muscles in certain subjects ipsilaterally decreased the static compliance with increased contraction of the stapedius muscle, which probably occurs to immobilise the tympanic membrane and protect the inner ear from loud sound. Evaluation of unilateral tight eyelid closure and the subsequent change in the contralateral vertical medial eyebrow position as well as a measurement of the static compliance for the stapedius muscle tone has revealed muscle hyperactivity of grimacing muscles.

Innervation of the cow's inner ear derived from micro-computed tomography

NASA Astrophysics Data System (ADS)

Costeur, Loic; Mennecart, Bastien; Khimchenko, Anna; Müller, Bert; Schulz, Georg

2017-09-01

The innervation of the inner ear has been thoroughly investigated in humans and in some animal models such as the guinea pig, the rabbit, the cat, the dog, the rat, the pig and some monkeys. Ruminant inner ears are still poorly known and their innervation was never investigated despite its potential interest in phylogenetic reconstructions. Following earlier works on the ontogeny of the cow's ear, we expand our understanding of this structure by reconstructing the fine innervation pattern of the inner ear of the cow in two ontogenetic stages, at 7 months gestation and at an adult age. Since we work on dry skeletal specimens, only the endocast of the innervation inside the petrosal bone was reconstructed up to the internal acoustic meatus. The paths of the facial and vestibulocochlear nerves could be reconstructed together with that of the spiral ganglion canal. The nerves have a very fibrous pattern. The bony cavities of the ampular and utricular branches of the vestibulocochlear nerve could also be reconstructed. Our observations confirm that not all bony structures are present in foetal stages since the branch of cranial nerve VII is not visible on the foetus but very broad on the adult stage. The fibrous pattern within the modiolus connecting the spiral canal to the cochlear nerve is also less dense than in the adult stage. The shape of the branch of cranial nerve VII is very broad in the cow ending in a large hiatus Fallopii; this, together with the above-mentioned particularities, could constitute relevant observations for phylogenetical purposes when more data will be made available.

Effects of hindlimb unloading on neuromuscular development of neonatal rats

NASA Technical Reports Server (NTRS)

Huckstorf, B. L.; Slocum, G. R.; Bain, J. L.; Reiser, P. M.; Sedlak, F. R.; Wong-Riley, M. T.; Riley, D. A.

2000-01-01

We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.

Avoiding Complications in Abdominal Wall Surgery: A Mathematical Model to Predict the Course of the Motor Innervation of the Rectus Abdominis.

PubMed

Tessone, Ariel; Nava, Maurizio; Blondeel, Phillip; Spano, Andrea

2016-02-01

Ever since its introduction, the transverse rectus abdominis myocutaneous flap has become the mainstay of autologous breast reconstruction. However, concerns regarding donor site morbidity due to the breach of abdominal wall musculature integrity soon followed. Muscle-sparing techniques, eventually eliminating the muscle from the flap all-together with the deep inferior epigastric artery perforator flap, did not eliminate the problem of abdominal wall weakness. This led to the conclusion that motor innervation might be at fault. Studies have shown that even in the presence of an intact rectus abdominis muscle, and an intact anterior rectus sheath, denervation of the rectus abdominis muscle results in significant abdominal wall weakness leading to superior and inferior abdominal bulges, and abdominal herniation. Our aim was to establish a mathematical model to predict the location of the motor innervation to the rectus abdominis muscle, and thus provide surgeons with a tool that will allow them to reduce abdominal morbidity during deep inferior epigastric artery perforator and free muscle-sparing transverse rectus abdominis myocutaneous surgery. We dissected 42 cadaveric hemiabdomens and mapped the course of the thoracolumbar nerves. We then standardized and analyzed our findings and presented them as a relative map which can be adjusted to body type and dimensions. Our dissections show that the motor innervation is closely related to the lateral vascular supply. Thus, when possible, we support the preferred utilization of the medial vascular supply, and the preservation of the lateral supply and motor innervation.

Neuroanatomical Evidence for Catecholamines as Modulators of Audition and Acoustic Behavior in a Vocal Teleost.

PubMed

Forlano, Paul M; Sisneros, Joseph A

2016-01-01

The plainfin midshipman fish (Porichthys notatus) is a well-studied model to understand the neural and endocrine mechanisms underlying vocal-acoustic communication across vertebrates. It is well established that steroid hormones such as estrogen drive seasonal peripheral auditory plasticity in female Porichthys in order to better encode the male's advertisement call. However, little is known of the neural substrates that underlie the motivation and coordinated behavioral response to auditory social signals. Catecholamines, which include dopamine and noradrenaline, are good candidates for this function, as they are thought to modulate the salience of and reinforce appropriate behavior to socially relevant stimuli. This chapter summarizes our recent studies which aimed to characterize catecholamine innervation in the central and peripheral auditory system of Porichthys as well as test the hypotheses that innervation of the auditory system is seasonally plastic and catecholaminergic neurons are activated in response to conspecific vocalizations. Of particular significance is the discovery of direct dopaminergic innervation of the saccule, the main hearing end organ, by neurons in the diencephalon, which also robustly innervate the cholinergic auditory efferent nucleus in the hindbrain. Seasonal changes in dopamine innervation in both these areas appear dependent on reproductive state in females and may ultimately function to modulate the sensitivity of the peripheral auditory system as an adaptation to the seasonally changing soundscape. Diencephalic dopaminergic neurons are indeed active in response to exposure to midshipman vocalizations and are in a perfect position to integrate the detection and appropriate motor response to conspecific acoustic signals for successful reproduction.

Tibial and fibular nerves evaluation using intraoperative electromyography in rats.

PubMed

Nepomuceno, André Coelho; Politani, Elisa Landucci; Silva, Eduardo Guandelini da; Salomone, Raquel; Longo, Marco Vinicius Losso; Salles, Alessandra Grassi; Faria, José Carlos Marques de; Gemperli, Rolf

2016-08-01

To evaluate a new model of intraoperative electromyographic (EMG) assessment of the tibial and fibular nerves, and its respectives motor units in rats. Eight Wistar rats underwent intraoperative EMG on both hind limbs at two different moments: week 0 and week 12. Supramaximal electrical stimulation applied on sciatic nerve, and compound muscle action potential recorded on the gastrocnemius muscle (GM) and the extensor digitorum longus muscle (EDLM) through electrodes at specifics points. Motor function assessment was performaced through Walking Track Test. Exposing the muscles and nerves for examination did not alter tibial (p=0.918) or fibular (p=0.877) function between the evaluation moments. Electromyography of the GM, innervated by the tibial nerve, revealed similar amplitude (p=0.069) and latency (p=0.256) at week 0 and at 12 weeks, creating a standard of normality. Meanwhile, electromyography of the EDLM, innervated by the fibular nerve, showed significant differences between the amplitudes (p=0.003) and latencies (p=0.021) at the two different moments of observation. Intraoperative electromyography determined and quantified gastrocnemius muscle motor unit integrity, innervated by tibial nerve. Although this study was not useful to, objectively, assess extensor digitorum longus muscle motor unit, innervated by fibular nerve.

Slit/Robo Signaling Mediates Spatial Positioning of Spiral Ganglion Neurons during Development of Cochlear Innervation

PubMed Central

Wang, Sheng-zhi; Ibrahim, Leena A.; Kim, Young J.; Gibson, Daniel A.; Leung, Haiwen C.; Yuan, Wei; Zhang, Ke K.; Tao, Huizhong W.

2013-01-01

During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations. PMID:23884932

Genetically identified spinal interneurons integrating tactile afferents for motor control

PubMed Central

Panek, Izabela; Farah, Carl

2015-01-01

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing. PMID:26445867

Origins of serotonin innervation of forebrain structures

NASA Technical Reports Server (NTRS)

Kellar, K. J.; Brown, P. A.; Madrid, J.; Bernstein, M.; Vernikos-Danellis, J.; Mehler, W. R.

1977-01-01

The tryptophan hydroxylase activity and high-affinity uptake of (3H) serotonin ((3H)5-HT) were measured in five discrete brain regions of rats following lesions of the dorsal or median raphe nuclei. Dorsal raphe lesions reduced enzyme and uptake activity in the striatum only. Median raphe lesions reduced activities in the hippocampus, septal area, frontal cortex, and, to a lesser extent, in the hypothalamus. These data are consistent with the suggestion that the dorsal and median raphe nuclei are the origins of two separate ascending serotonergic systems - one innervating striatal structures and the other mesolimbic structures, predominantly. In addition, the data suggest that measurements of high-affinity uptake of (3H)5-HT may be a more reliable index of innervation than either 5-HT content or tryptophan hydroxylase activity.

Comparative study of the innervation of the facila disc of selected mammals.

PubMed

Montagna, W; Roman, N A; Macpherson, E

1975-11-01

The greatest concentration of sensory nerves in the muzzle and facial disc of mammals is in the nose. In most nocturnal mammals, these nerves penetrate the epidermis of the naked nose either or in bundles which resemble the corpuscles of Eimer. The hair follicles around the nose, lips, and eyes, as well as the heaviply innervated vibrissae follicles found in all hairy mammals except man, are well innervated; those elsewhaere are not. Everywhere on the human body both large and small follicles abound in sensory nerves. These morphologic observations suggest that in most mammals the most sensitivie areas of the skin are at the anterior and posterior ends (not reported here), and that human skin is better equipped for cutaneous sensibility than that of any other mammal.

The kidney in the pathogenesis of hypertension: the role of renal nerves.

PubMed

DiBona, G F

1985-04-01

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.

Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

PubMed Central

Hegedus, J; Putman, C T; Tyreman, N; Gordon, T

2008-01-01

The present study investigated motor unit (MU) loss in a murine model of familial amyotrophic lateral sclerosis (ALS). The fast-twitch tibialis anterior (TA) and medial gastrocnemius (MG) muscles of transgenic SOD1G93A and SOD1WT mice were studied during the presymptomatic phase of disease progression at 60 days of age. Whole muscle maximum isometric twitch and tetanic forces were 80% lower (P < 0.01) in the TA muscles of SOD1G93A compared to SOD1WT mice. Enumeration of total MU numbers within TA muscles showed a 60% reduction (P < 0.01) within SOD1G93A mice (38 ± 7) compared with SOD1WT controls (95 ± 12); this was attributed to a lower proportion of the most forceful fast-fatigable (FF) MU in SOD1G93A mice, as seen by a significant (P < 0.01) leftward shift in the cumulative frequency histogram of single MU forces. Similar patterns of MU loss and corresponding decreases in isometric twitch force were observed in the MG. Immunocytochemical analyses of the entire cross-sectional area (CSA) of serial sections of TA muscles stained with anti-neural cell adhesion molecule (NCAM) and various monoclonal antibodies for myosin heavy chain (MHC) isoforms showed respective 65% (P < 0.01) and 28% (P < 0.05) decreases in the number of innervated IIB and IID/X muscle fibres in SOD1G93A, which paralleled the 60% decrease (P < 0.01) in the force generating capacity of individual fibres. The loss of fast MUs was partially compensated by activity-dependent fast-to-slower fibre type transitions, as determined by increases (P < 0.04) in the CSA and proportion of IIA fibres (from 4% to 14%) and IID/X fibres (from 31% to 39%), and decreases (P < 0.001) in the CSA and proportion of type IIB fibres (from 65% to 44%). We conclude that preferential loss of IIB fibres is incomplete at 60 days of age, and is consistent with a selective albeit gradual loss of FF MUs that is not fully compensated by sprouting of the remaining motoneurons that innervate type IIA or IID/X muscle fibres. Our findings indicate that disease progression in fast-twitch muscles of SOD1G93A mice involves parallel processes: (1) gradual selective motor axon die-back of the FF motor units that contain large type IIB muscle fibres, and of fatigue-intermediate motor units that innervate type IID/X muscle fibres, and (2) activity-dependent conversion of motor units to those innervated by smaller motor axons innervating type IIA fatigue-resistant muscle fibres. PMID:18467368

Task-Evoked Pupillary Responses and Cognitive Processing.

DTIC Science & Technology

1980-02-01

Yingling, C.D., and Skinner, J.E. Gating of thalanic input to cerebral cortex by nucleus reticularis thalami. In J.E. Desmedt (Ed.), Attention, voluntary...innervated. Peripheral control of these muscles originates In the nucleus Edinger-Westphal (located within the third nerve nucleus at the level of the...thalamus is a thin neuronal shell, the reticular nucleus of the thalamus (Carpenter, 1978). Most of the axons from this shell enter the dorsal thalamus

Nerve Repulsion by the Lens and Cornea during Cornea Innervation is Dependent on Robo-Slit Signaling and Diminishes with Neuron Age

PubMed Central

Schwend, Tyler; Lwigale, Peter Y.; Conrad, Gary W.

2012-01-01

The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5-8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slit 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation, thus allowing nerves to find the Slit-expressing cornea permissive for growth cones. PMID:22236962

The Physiology of Bone Pain. How Much Do We Really Know?

PubMed Central

Nencini, Sara; Ivanusic, Jason J.

2016-01-01

Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID:27199772

The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease

PubMed Central

Razgado-Hernandez, Luis F.; Espadas-Alvarez, Armando J.; Reyna-Velazquez, Patricia; Sierra-Sanchez, Arturo; Anaya-Martinez, Veronica; Jimenez-Estrada, Ismael; Bannon, Michael J.; Martinez-Fong, Daniel; Aceves-Ruiz, Jorge

2015-01-01

The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson’s disease. PMID:25693197

Effects of Microgravity on Quail Eye Development

NASA Technical Reports Server (NTRS)

Conrad, Gary W.

1996-01-01

During embryonic development, the most exposed tissue of the eye, the cornea, becomes differentially bulged outward because of constant intraocular pressure (IOP). The component cells of the cornea secrete a unique, paracrystalline extracellular matrix (the stroma) composed of orthogonal plies of collagen fibrils and proteoglycans. The cornea remains avascular, becomes transparent, and becomes more densely innervated than any other region on the surface of the body. Corneas from chicken embryos that flew on STS-47 contain many more cellular processes in the outermost region of the stroma (Bowman's Layer) than any corresponding region of control corneas. These processes appear to be cross-sections of cytoplasmic extensions of cells and are found in that region of Bowman's Layer immediately beneath the basal lamina of the corneal epithelium. Here, we propose to compare corneas of quail that flew in space on Mir-1 with those of ground controls to determine if the same unusual cellular processes are seen as in the space-flown chicken corneas. In the central regions of such space-flown corneas, the processes appear to be either portions of basal epithelial cells whose pseudopodial extensions have migrated down through their own basal lamina into the stroma, or corneal nerves that have innervated the corneal stroma in an unusual manner. Eyeballs of embryos fixed on Mir-1, control embryos fixed at KSC and clinostated embryos fixed at KSU, will provide corneas for this study. Electron microscopy will be used to assess the distribution of the cellular processes in Bowman's Layer in the central region of each cornea. Attempts also will be made to determine the relative glycosaminoglycan distributions in the corneal stromas by indirect immunofluorscence and to record whole-mount staining patterns of the corneal nerves.

Fate of 3H-thymidine labelled myogenic cells in regeneration of muscle isografts.

PubMed

Gutmann, E; Mares, V; Stichová, J

1976-03-05

Intact and denervated extensor digitorum longus (EDL) muscles of 20-day-old inbred Lewis-Wistar rats were labelled with 3H-thymidine. Ninety minutes after the injection of the isotope 4.0% of the nuclei were labelled in the intact (i.e. innervated) and 9.6% in the muscles, denervated 3 days before administration of the isotope. The labelled EDL muscles were grafted into the bed of the previously removed EDL muscles of inbred animals and these isografts were studied 30 days later. In the EDL muscles, regenerated from innervated isografts only occasionally labelled endothelial cells were found whereas in the muscles regenerated from denervated isografts also parenchymal muscle nuclei were regularly labelled. The incidence of labelled nuclei in the regenerated EDL muscles was, however, about 20 times lower than in the donor EDL muscles. The presen experiments provide a direct proof of utilization of donor satelite cell nuclei for regeneration in grafted muscle tissue. With respect to the low incidence of labelled nuclei in regenerated EDL muscles, other sources of cells apparently also contribute to the regeneration process.

Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor (CaSR)

PubMed Central

Vizard, Thomas N.; O'Keeffe, Gerard W.; Gutierrez, Humberto; Kos, Claudine H.; Riccardi, Daniela; Davies, Alun M.

2009-01-01

The extracellular calcium-sensing receptor (CaSR) monitors the systemic extracellular free ionized calcium level ([Ca2+]o) in organs involved in systemic [Ca2+]o homeostasis. However, the CaSR is also expressed in the nervous system where its role is unknown. Here we find high levels of the CaSR in perinatal mouse sympathetic neurons when their axons are innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca2+]o, using CaSR agonists and antagonists or expressing a dominant-negative CaSR markedly affects neurite growth in vitro Sympathetic neurons lacking the CaSR have smaller neurite arbors in vitro, and sympathetic innervation density is reduced in CaSR-deficient mice in vivo. Hippocampal pyramidal neurons, which also express the CaSR, have smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for the CaSR in regulating the growth of neural processes in the peripheral and central nervous systems. PMID:18223649

Development and regeneration of the electric organ.

PubMed

Zakon, H H; Unguez, G A

1999-05-01

The electric organ has evolved independently from muscle in at least six lineages of fish. How does a differentiated muscle cell change its fate to become an electrocyte? Is the process by which this occurs similar in different lineages? We have begun to answer these questions by studying the formation and maintenance of electrocytes in the genus Sternopygus, a weakly electric teleost. Electrocytes arise from the fusion of fully differentiated muscle fibers, mainly those expressing fast isoforms of myosin. Electrocytes briefly co-express sarcomeric proteins, such as myosin and tropomyosin, and keratin, a protein not found in mature muscle. The sarcomeric proteins are subsequently down-regulated, but keratin expression persists. We investigated whether the maintenance of the electrocyte phenotype depends on innervation. We found that, after spinal cord transection, which silences the electromotor neurons that innervate the electrocytes, or destruction of the spinal cord, which denervates the electrocytes, mature electrocytes re-express sarcomeric myosin and tropomyosin, although keratin expression persists. Ultrastructural examination of denervated electrocytes revealed nascent sarcomeres. Thus, the maintenance of the electrocyte phenotype depends on neural activity.

Nervous control of photophores in luminescent fishes.

PubMed

Zaccone, Giacomo; Abelli, Luigi; Salpietro, Lorenza; Zaccone, Daniele; Macrì, Battesimo; Marino, Fabio

2011-07-01

Functional studies of the autonomic innervation in the photophores of luminescent fishes are scarce. The majority of studies have involved either the stimulation of isolated photophores or the modulatory effects of adrenaline-induced light emission. The fish skin is a highly complex organ that performs a wide variety of physiological processes and receives extensive nervous innervations. The latter includes autonomic nerve fibers of spinal sympathetic origin having a secretomotor function. More recent evidence indicates that neuropeptide-containing nerve fibers, such as those that express tachykinin and its NK1 receptor, neuropeptide Y, or nitric oxide, may also play an important role in the nervous control of photophores. There is no anatomical evidence that shows that nNOS positive (nitrergic) neurons form a population distinct from the secretomotor neurons with perikarya in the sympathetic ganglia. The distribution and function of the nitrergic nerves in the luminous cells, however, is less clear. It is likely that the chemical properties of the sympathetic postganglionic neurons in the ganglia of luminescent fishes are target-specific, such as observed in mammals. Copyright © 2010 Elsevier GmbH. All rights reserved.

Beyond Columnar Organization: Cell Type- and Target Layer-Specific Principles of Horizontal Axon Projection Patterns in Rat Vibrissal Cortex

PubMed Central

Narayanan, Rajeevan T.; Egger, Robert; Johnson, Andrew S.; Mansvelder, Huibert D.; Sakmann, Bert; de Kock, Christiaan P.J.; Oberlaender, Marcel

2015-01-01

Vertical thalamocortical afferents give rise to the elementary functional units of sensory cortex, cortical columns. Principles that underlie communication between columns remain however unknown. Here we unravel these by reconstructing in vivo-labeled neurons from all excitatory cell types in the vibrissal part of rat primary somatosensory cortex (vS1). Integrating the morphologies into an exact 3D model of vS1 revealed that the majority of intracortical (IC) axons project far beyond the borders of the principal column. We defined the corresponding innervation volume as the IC-unit. Deconstructing this structural cortical unit into its cell type-specific components, we found asymmetric projections that innervate columns of either the same whisker row or arc, and which subdivide vS1 into 2 orthogonal [supra-]granular and infragranular strata. We show that such organization could be most effective for encoding multi whisker inputs. Communication between columns is thus organized by multiple highly specific horizontal projection patterns, rendering IC-units as the primary structural entities for processing complex sensory stimuli. PMID:25838038

Targeted taste cell-specific overexpression of brain-derived neurotrophic factor in adult taste buds elevates phosphorylated TrkB protein levels in taste cells, increases taste bud size, and promotes gustatory innervation.

PubMed

Nosrat, Irina V; Margolskee, Robert F; Nosrat, Christopher A

2012-05-11

Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-gustducin promoter coupling BDNF expression to the postnatal expression of gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system.

Innervation of the cricothyroid muscle by extralaryngeal branches of the recurrent laryngeal nerve.

PubMed

Miyauchi, Akira; Masuoka, Hiroo; Nakayama, Ayako; Higashiyama, Takuya

2016-05-01

A major concern in thyroid surgery is possible changes in the patient's voice due to dysfunction of the laryngeal muscles. The classical understanding of the anatomy is that the cricothyroid muscle (CTM) is innervated solely by the external branch of the superior laryngeal nerve (EBSLN), and the endolaryngeal muscles are covered only by the recurrent laryngeal nerve (RLN). Meticulous anatomical studies found communication between these nerves. Recent neurophysiological studies revealed cross-innervations among these nerve-muscle sets. Here, we report innervation of the CTM by extralaryngeal branches of the RLN. Clinical observation during thyroid surgery at a hospital center for thyroid diseases. During thyroid cancer surgeries, we encountered four adult Japanese patients who had an extralaryngeal branch of the RLN, the electrical stimulation of which showed contraction of the CTM. The EBSLN and RLN were electrically stimulated. Responses were evaluated by visual observation of contraction of the CTM and palpable laryngeal twitch of the endolaryngeal muscles. Electromyographic studies were also performed in two patients. Five of the seven RLNs examined showed contraction of the CTM on stimulation. Four of these five RLNs had an extralaryngeal branch that showed contraction of the CTM on stimulation. Stimulation of the RLN proximal to the branch yielded contraction of the CTM and laryngeal twitch, whereas stimulation of the RLN distal to the branch yielded only laryngeal twitch. Extralaryngeal branches of the RLN innervated the CTM in four patients. This phenomenon might influence voice changes following thyroid surgery. 4. Laryngoscope, 126:1157-1162, 2016. Laryngoscope published by Wiley on behalf of the American Laryngological, Rhinological and Otological Society, Inc, “The Triological Society” and American Laryngological Association (the “Owner”).

Targeted Taste Cell-specific Overexpression of Brain-derived Neurotrophic Factor in Adult Taste Buds Elevates Phosphorylated TrkB Protein Levels in Taste Cells, Increases Taste Bud Size, and Promotes Gustatory Innervation*

PubMed Central

Nosrat, Irina V.; Margolskee, Robert F.; Nosrat, Christopher A.

2012-01-01

Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-gustducin promoter coupling BDNF expression to the postnatal expression of gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system. PMID:22442142

Developing grasshopper neurons show variable levels of guanylyl cyclase activity on arrival at their targets.

PubMed

Ball, E E; Truman, J W

1998-04-27

The ability of certain grasshopper neurons to respond to exogenously applied donors of nitric oxide (NO) by producing cyclic GMP (cGMP) depends on their developmental state. ODQ, a selective blocker of NO-sensitive guanylyl cyclase, blocks cGMP production at 10(-5) M, thus confirming the nature of the response. Experiments in which the distal axon is separated from its proximal stump before application of an NO donor show that guanylyl cyclase is distributed uniformly throughout the neuron. In the locust abdomen, where segments are formed sequentially, the pattern of guanylyl cyclase up-regulation is predictable and sequential from anterior to posterior. There are two patterns of innervation by cGMP-expressing motor neurons. In the first, typified by muscle 187, an innervating neuron begins to be NO responsive on arrival at its muscle and continues to be so over most of the remainder of embryonic development, including the formation of motor end plates. In the second, typified by a neuron innervating muscle 191, the neuron extends well along the muscle, apparently laying down a number of sites of contact with it, before it becomes NO responsive. In both patterns, however, NO responsiveness marks the neuron's transition from growth cone elongation to the production of lateral branches. Individual muscles receive innervation from multiple motor neurons, some of which express transient NO sensitivity during development and others which do not. With the exception of the leg motor neuron SETi, the first motor neuron to reach any muscle is usually not NO responsive. We suggest that cGMP plays a role in, or reflects, the early stages of communication between a target and specific innervating neurons.

Analysis of fiber-type differences in reporter gene expression of β-gal transgenic muscle.

PubMed

Tai, Phillip W L; Smith, Catherine L; Angello, John C; Hauschka, Stephen D

2012-01-01

β-galactosidase (β-gal) is among the most frequently used markers for studying a wide variety of biological mechanisms, e.g., gene expression, cell migration, stem cell conversion to different cell types, and gene silencing. Many of these studies require the histochemical detection of relative β-gal levels in tissue cross-sections mounted onto glass slides and visualized by microscopy. This is particularly useful for the analysis of promoter activity in skeletal muscle tissue since the β-gal levels can vary dramatically between different anatomical muscles and myofiber types. The differences in promoter activity can be due to a myofiber's developmental history, innervation, response to normal or experimental physiological signals, and its disease state. It is thus important to identify the individual fiber types within muscle cross-sections and to correlate these with transgene expression signals. Here, we provide a detailed description of how to process and analyze muscle tissues to determine the fiber-type composition and β-gal transgene expression within cryosections.

The neurobiology of social play and its rewarding value in rats

PubMed Central

Vanderschuren, Louk J.M.J.; Achterberg, E.J. Marijke; Trezza, Viviana

2016-01-01

In the young of many mammalian species, including humans, a vigorous and highly rewarding social activity is abundantly expressed, known as social play behaviour. Social play is thought to be important for the development of social, cognitive and emotional processes and their neural underpinnings, and it is disrupted in pediatric psychiatric disorders. Here, we summarize recent progress in our understanding of the brain mechanisms of social play behaviour, with a focus on its rewarding properties. Opioid, endocannabinoid, dopamine and noradrenaline systems play a prominent role in the modulation of social play. Of these, dopamine is particularly important for the motivational properties of social play. The nucleus accumbens has been identified as a key site for opioid and dopamine modulation of social play. Endocannabinoid influences on social play rely on the basolateral amygdala, whereas noradrenaline modulates social play through the basolateral amygdala, habenula and prefrontal cortex. In sum, social play behaviour is the result of coordinated activity in a network of corticolimbic structures, and its monoamine, opioid and endocannabinoid innervation. PMID:27587003

The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies.

PubMed

Lehner, Małgorzata; Taracha, Ewa; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Kołomańska, Paulina; Skórzewska, Anna; Maciejak, Piotr; Szyndler, Janusz; Bidziński, Andrzej; Płaźnik, Adam

2008-10-10

In this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear-freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS--high sensitivity rats, and LS--low sensitivity rats, selected arbitrarily according to their behavior in the 'flinch-jump' pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.

Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice.

PubMed

Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan; Rehfeld, Jens F; Friis-Hansen, Lennart

2010-09-01

The suprachiasmatic nucleus (SCN) is the principal pacemaker driving circadian rhythms of physiology and behaviour. Neurons within the SCN express both classical and neuropeptide transmitters which regulate clock functions. Cholecyctokinin (CCK) is a potent neurotransmitter expressed in neurons of the mammalian SCN, but its role in circadian timing is not known. In the present study, CCK was demonstrated in a distinct population of neurons located in the shell region of the SCN and in a few cells in the core region. The CCK neurons did not express vasopressin or vasoactive intestinal peptide. However, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of cFOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar τ, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting of the clock or in regulating core clock function. The expression of CCK in a subpopulation of neurons, which do not belonging to either the VIP or AVP cells but which have synaptic contacts to both cell types and reverse innervation of CCK neurons from VIP neurons, suggests that the CCK neurons may act in non-photic regulation within the clock and/or, via CCK projections, mediate clock information to hypothalamic nuclei. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Short and long sympathetic-sensory feedback loops in white fat

PubMed Central

Ryu, Vitaly

2014-01-01

We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129+PRV152-colocalized neurons (∼50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (>60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions. PMID:24717676

Lesions of the dopaminergic innervation of the nucleus accumbens medial shell delay the generation of preference for sucrose, but not of sexual pheromones.

PubMed

Martínez-Hernández, José; Lanuza, Enrique; Martínez-García, Fernando

2012-01-15

Male sexual pheromones are rewarding stimuli for female mice, able to induce conditioned place preference. To test whether processing these natural reinforcing stimuli depends on the dopaminergic innervation of the nucleus accumbens, as for other natural rewards, we compare the effects of specific lesions of the dopaminergic innervation of the medial shell of the nucleus accumbens on two different appetitive behaviours, 'pheromone seeking' and sucrose preferential intake. Female mice, with no previous experience with either adult male chemical stimuli or with sucrose, received injections of 6-hydroxydopamine (or vehicle) in the medial shell of the accumbens. Then, we analyzed their preference for male soiled-bedding and their preferential intake of a sucrose solution, with particular emphasis on the dynamics of acquisition of both natural rewards. The results indicate that both lesioned and sham animals showed similar preference for male sexual pheromones, which was constant along the test (linear dynamics). In contrast, lesioned animals differed from sham operated mice in the dynamics of sucrose consumption in their first test of sucrose preference. Sham animals showed an initial sucrose preference followed by preference for water, which can be interpreted as sucrose neophobia. Lesioned animals showed no preference at the beginning of the test, and a delayed sucrose preference appeared followed by a delayed neophobia. The next day, during a second sucrose-preference test, both groups displayed comparable and sustained preferential sucrose intake. Therefore, dopamine in the medial shell of the nucleus accumbens has a different role on the reward of sexual pheromones and sucrose. Copyright © 2011 Elsevier B.V. All rights reserved.

Dopamine Innervation in the Thalamus: Monkey versus Rat

PubMed Central

García-Cabezas, Miguel Ángel; Martínez-Sánchez, Patricia; Sánchez-González, Miguel Ángel; Garzón, Miguel

2009-01-01

We recently identified the thalamic dopaminergic system in the human and macaque monkey brains, and, based on earlier reports on the paucity of dopamine in the rat thalamus, hypothesized that this dopaminergic system was particularly developed in primates. Here we test this hypothesis using immunohistochemistry against the dopamine transporter (DAT) in adult macaque and rat brains. The extent and density of DAT-immunoreactive (-ir) axons were remarkably greater in the macaque dorsal thalamus, where the mediodorsal association nucleus and the ventral motor nuclei held the densest immunolabeling. In contrast, sparse DAT immunolabeling was present in the rat dorsal thalamus; it was mainly located in the mediodorsal, paraventricular, ventral medial, and ventral lateral nuclei. The reticular nucleus, zona incerta, and lateral habenular nucleus held numerous DAT-ir axons in both species. Ultrastructural analysis in the macaque mediodorsal nucleus revealed that thalamic interneurons are a main postsynaptic target of DAT-ir axons; this suggests that the marked expansion of the dopamine innervation in the primate in comparison to the rodent thalamus may be related to the presence of a sizable interneuron population in primates. We remark that it is important to be aware of brain species differences when using animal models of human brain disease. PMID:18550594

The structure and function of serially homologous leg motor neurons in the locust. I. Anatomy.

PubMed

Wilson, J A

1979-01-01

Twenty-one prothoracic and 17 mesothoracic motor neurons innervating leg muscles have been identified physiologically and subsequently injected with dye from a microelectrode. A tract containing the primary neurites of motor neurons innervating the retractor unquis, levator and depressor tarsus, flexor tibiae, and reductor femora is described. All motor neurons studied have regions in which their dendritic branches overlap with those of other leg motor neurons. Identified, serially homologous motor neurons in the three thoracic ganglia were found to have: (1) cell bodies at similar locations and morphologically similar primary neurites (e.g., flexor tibiae motor neurons), (2) cell bodies at different locations in each ganglion and morphologically different primary neurites in each ganglion (e.g., fast retractor unguis motor neurons), or (3) cell bodies at similar locations and morphologically similar primary neurites but with a functional switch in one ganglion relative to the function of the neurons in the other two ganglia. As an example of the latter, the morphology of the metathoracic slow extensor tibiae (SETi) motor neurons was similar to that of pro- and mesothoracic fast extensor tibiae (FETi) motor neurons. Similarly the metathoracic FETi bears a striking resemblance to the pro- and the mesothoracic SETi. It is proposed that in the metathoracic ganglion the two extensor tibiae motor neurons have switched functions while retaining similar morphologies relative to the structure and function of their pro- and mesothoracic serial homologues.

How many mechanosensory organs in the bushcricket leg? Neuroanatomy of the scolopidial accessory organ in Tettigoniidae (Insecta: Orthoptera).

PubMed

Strauß, Johannes; Riesterer, Anja S; Lakes-Harlan, Reinhard

2016-01-01

The subgenual organ and associated scolopidial organs are well studied in Orthoptera and related taxa. In some insects, a small accessory organ or Nebenorgan is described posterior to the subgenual organ. In Tettigoniidae (Ensifera), the accessory organ has only been noted in one species though tibial sensory organs are well studied for neuroanatomy and physiology. Here, we use axonal tracing to analyse the posterior subgenual organ innervated by the main motor nerve. Investigating seven species from different groups of Tettigoniidae, we describe a small group of scolopidial sensilla (5-9 sensory neurons) which has features characteristic of the accessory organ: posterior tibial position, innervation by the main leg nerve rather than by the tympanal nerve, orientation of dendrites in proximal or ventro-proximal direction in the leg, and commonly association with a single campaniform sensillum. The neuroanatomy is highly similar between leg pairs. We show differences in the innervation in two species of the genus Poecilimon as compared to the other species. In Poecilimon, the sensilla of the accessory organ are innervated by one nerve branch together with the subgenual organ. The results suggest that the accessory organ is part of the sensory bauplan in the leg of Tettigoniidae and probably Ensifera. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of vestibular function: biochemical, morphological and electronystagmographical assessment in the rat.

PubMed

Meza, G; Acuña, D; Gutiérrez, A; Merchan, J M; Rueda, J

1996-07-01

Glutamate decarboxylase and choline acetyltransferase were measured in homogenated ampullar cristae of rats during development from postnatal day 13 to 60 to determine changes in levels of these enzymes during early postnatal development. Afferent and efferent innervation of the hair cells of the developing cristae were studied using electron microscopy. In parallel, groups of rats, postrotatory nystagmus were used to assess the development of semicircular canal function during the same time interval. The level of glutamate decarboxylase was high on postnatal day 15 and did not change notably over the remaining days to day 60. Activity of choline acetyltransferase was nearly absent at day 15, but reached levels seen in mature animals by day 17, and remained almost unchanged thereafter. In contrast, as revealed by electronmicroscopy, afferent and efferent innervation appeared to be mature by day 8. Postrotatory nystagmus presented the adult-like features from day 19 onward. According to these results, a role for glutamate decarboxylase in afferent transmission is suggested by the parallel development of levels of glutamate decarboxylase and afferent innervation of the ampullary cristae. The finding of a similar time course of development of choline acetyltransferase levels and postrotatory nystagmus suggests that a cholinergic efferent innervation is involved in the onset of vestibular-ocular function.

Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

PubMed

Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

2016-10-01

Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?

PubMed

Spang, C; Alfredson, H

2017-06-01

Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin and eosin, H and E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. IV.

Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow – Implication for treatment?

PubMed Central

Spang, C.; Alfredson, H.

2017-01-01

Background: Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Methods: Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin & eosin, H&E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). Results: All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. Conclusion: The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. Level of Evidence: IV. PMID:28574416

[Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

PubMed

Chertok, V M; Kotsiuba, A E; Babich, E V

2009-01-01

Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

PubMed Central

Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C.H.

2016-01-01

Abstract. The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs. PMID:27921067

Retrograde double-labeling demonstrates convergent afferent innervation of the prostate and bladder.

PubMed

Lee, Sanghee; Yang, Guang; Xiang, William; Bushman, Wade

2016-06-01

Prostatic inflammation is a common histologic finding in men with lower urinary tract symptoms (LUTS). It has been postulated that prostatic inflammation could sensitize afferent neurons innervating the bladder and thereby produce changes in voiding behavior. In support of this, we demonstrate an anatomic basis for pelvic cross-talk involving the prostate and bladder. Retrograde labeling was performed by an application of a neuro-tracer Fast Blue (FB) to one side of either the anterior prostate (AP), dorsal lateral prostate (DLP)/ventral prostate (VP), bladder, or seminal vesicle (SV). Examination of dorsal root ganglion (DRG) neuron labeling revealed shared afferent innervation of the prostate and bladder at spinal segments of T13, L1, L2, L6, and S1. Dual labeling was performed by an application of FB and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyaine perchlorate (DiI) to the AP and bladder, respectively. We observed double-labeled DRG neurons at T13, L1, L2, L6, and S1--a finding that proves convergent innervation of prostate and bladder. Our observations demonstrate the potential for neural cross-talk between the prostate and bladder and support a postulated mechanism that prostatic inflammation may induce hyper-sensitization of bladder afferents and produce irritative LUTS. © 2016 Wiley Periodicals, Inc.

Sensory Arsenal on the Stinger of the Parasitoid Jewel Wasp and Its Possible Role in Identifying Cockroach Brains

PubMed Central

Gal, Ram; Kaiser, Maayan; Haspel, Gal; Libersat, Frederic

2014-01-01

The parasitoid jewel wasp uses cockroaches as live food supply for its developing larva. To this end, the adult wasp stings a cockroach and injects venom directly inside its brain, turning the prey into a submissive ‘zombie’. Here, we characterize the sensory arsenal on the wasp’s stinger that enables the wasp to identify the brain target inside the cockroach’s head. An electron microscopy study of the stinger reveals (a) cuticular depressions innervated by a single mechanosensory neuron, which are presumably campaniform sensilla; and (b) dome-shaped structures innervated by a single mechanosensory neuron and 4–5 chemosensory neurons, which are presumably contact-chemoreceptive sensilla. Extracellular electrophysiological recordings from stinger afferents show increased firing rate in response to mechanical stimulation with agarose. This response is direction-selective and depends upon the concentration (density) of the agarose, such that the most robust response is evoked when the stinger is stimulated in the distal-to-proximal direction (concomitant with the penetration during the natural stinging behavior) and penetrating into relatively hard (0.75%–2.5%) agarose pellets. Accordingly, wasps demonstrate a normal stinging behavior when presented with cockroaches in which the brain was replaced with a hard (2.5%) agarose pellet. Conversely, wasps demonstrate a prolonged stinging behavior when the cockroach brain was either removed or replaced by a soft (0.5%) agarose pellet, or when stinger sensory organs were ablated prior to stinging. We conclude that the parasitoid jewel wasp uses at least mechanosensory inputs from its stinger to identify the brain within the head capsule of the cockroach prey. PMID:24586962

Follistatin: A Potential Anabolic Treatment for Re-Innervated Muscle

DTIC Science & Technology

2017-09-01

Observations: ELISA , muscle histology, nerve histology, etc.are pending and no final conclusions can be made. 1. 3-month Protein: a. Muscle Weight: No...and virus needed for the study and also helped in Pilot Study- ELISA . He presented the following abstract in VCU School of Medicine Student Research...denervation groups (1-6): ▪ Follistatin ELISA – Run the assay, collect data, and prepare to present data ▪ Muscle Histology – Process tissue, image the

Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

NASA Technical Reports Server (NTRS)

Zardetto-Smith, Andrea M.; Johnson, Alan Kim

1995-01-01

This study examined efferent output from the median preoptic nucleus (MNPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions. In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed. The results indicate the MNPO provides a topographic innervation of monoaminergic groups in the upper brainstem.

Standard operating procedures for neurophysiologic assessment of male sexual dysfunction.

PubMed

Giuliano, Francois; Rowland, David L

2013-05-01

Can neurophysiological testing in male patients with sexual dysfunction benefit the decision-making process? The answer remains unclear. To provide standard operating procedures for the neurophysiologic assessment of male sexual dysfunction. Medical literature was reviewed and combined with expert opinion of the authors. Bulbocavernosus reflex latency time, pudendal somatosensory evoked potentials, and sympathetic skin responses have been considered as potential candidates for the diagnosis and assessment of erectile dysfunction (ED). Currently, there is no consensus on a standardized methodology for these neurophysiological investigations in the overall assessment of ED. These procedures are unable to assess the integrity of the efferent parasympathetic proerectile penile innervation; accordingly, none of these assessment procedures is recommended for ED patients. Corpus cavernosum electromyography (CC-EMG) can detect abnormalities in cavernous smooth muscle although these alterations can be attributed both to damage to autonomic penile innervation and to degenerative processes of the cavernous smooth muscle. CC-EMG is still considered experimental. Evidence does not support that men with premature ejaculation (PE) are consistently characterized by penile hypersensitivity; accordingly, penile threshold determination is not recommended to in the diagnosis of PE. Neurophysiological investigation of other components of the penile sensory pathways in PE patients has not provided any definitive contribution to the diagnosis. No neurophysiological assessment procedures yield additional information that consistently aids in the assessment of PE and ED. © 2013 International Society for Sexual Medicine.

Schaffer Collateral Inputs to CA1 Excitatory and Inhibitory Neurons Follow Different Connectivity Rules.

PubMed

Kwon, Osung; Feng, Linqing; Druckmann, Shaul; Kim, Jinhyun

2018-05-30

Neural circuits, governed by a complex interplay between excitatory and inhibitory neurons, are the substrate for information processing, and the organization of synaptic connectivity in neural network is an important determinant of circuit function. Here, we analyzed the fine structure of connectivity in hippocampal CA1 excitatory and inhibitory neurons innervated by Schaffer collaterals (SCs) using mGRASP in male mice. Our previous study revealed spatially structured synaptic connectivity between CA3 and CA1 pyramidal cells (PCs). Surprisingly, parvalbumin-positive interneurons (PVs) showed a significantly more random pattern spatial structure. Notably, application of Peters' rule for synapse prediction by random overlap between axons and dendrites enhanced structured connectivity in PCs, but, by contrast, made the connectivity pattern in PVs more random. In addition, PCs in a deep sublayer of striatum pyramidale appeared more highly structured than PCs in superficial layers, and little or no sublayer specificity was found in PVs. Our results show that CA1 excitatory PCs and inhibitory PVs innervated by the same SC inputs follow different connectivity rules. The different organizations of fine scale structured connectivity in hippocampal excitatory and inhibitory neurons provide important insights into the development and functions of neural networks. SIGNIFICANCE STATEMENT Understanding how neural circuits generate behavior is one of the central goals of neuroscience. An important component of this endeavor is the mapping of fine-scale connection patterns that underlie, and help us infer, signal processing in the brain. Here, using our recently developed synapse detection technology (mGRASP and neuTube), we provide detailed profiles of synaptic connectivity in excitatory (CA1 pyramidal) and inhibitory (CA1 parvalbumin-positive) neurons innervated by the same presynaptic inputs (CA3 Schaffer collaterals). Our results reveal that these two types of CA1 neurons follow different connectivity patterns. Our new evidence for differently structured connectivity at a fine scale in hippocampal excitatory and inhibitory neurons provides a better understanding of hippocampal networks and will guide theoretical and experimental studies. Copyright © 2018 the authors 0270-6474/18/385140-13$15.00/0.

Anatomical study of the final common pathway for vocalization in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert

1989-01-01

Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

Responses of motor and sensory neurons of rodents to spaceflight

NASA Technical Reports Server (NTRS)

Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Edgerton, V. R.

2000-01-01

Spinal motoneurons innervating skeletal muscles comprised predominantly of high oxidative fibers, i.e. slow oxidative and fast oxidative glycolytic, have higher oxidative enzyme activities than motoneurons innervating skeletal muscles comprised primarily of low oxidative fibers, i.e. fast glycolytic. These findings suggest that there is a close relationship between the oxidative phosphorylation capacity of a motoneuron and of the muscle fibers that it innervates. Since some skeletal muscles become faster and less oxidative after 4-14 days of spaceflight, it might be expected that oxidative enzyme activities in some motoneurons also may decrease after spaceflight. In addition, there is significant muscular atrophy after even short spaceflights and, therefore, it may be expected that some motoneurons associated with these muscles also would atrophy. In the present paper, we examine the issue of whether spaceflight induces changes in the oxidative enzyme activity and/or size of spinal motoneurons.

Innervation of taste buds revealed with Brainbow-labeling in mouse.

PubMed

Zaidi, Faisal N; Cicchini, Vanessa; Kaufman, Daniel; Ko, Elizabeth; Ko, Abraham; Van Tassel, Heather; Whitehead, Mark C

2016-12-01

Nerve fibers that surround and innervate the taste bud were visualized with inherent fluorescence using Brainbow transgenic mice that were generated by mating the founder line L with nestin-cre mice. Multicolor fluorescence revealed perigemmal fibers as branched within the non-taste epithelium and ending in clusters of multiple rounded swellings surrounding the taste pore. Brainbow-labeling also revealed the morphology and branching pattern of single intragemmal fibers. These taste bud fibers frequently innervated both the peripheral bud, where immature gemmal cells are located, and the central bud, where mature, differentiated cells are located. The fibers typically bore preterminal and terminal swellings, growth cones with filopodia, swellings, and rounded retraction bulbs. These results establish an anatomical substrate for taste nerve fibers to contact and remodel among receptor cells at all stages of their differentiation, an interpretation that was supported by staining with GAP-43, a marker for growing fibers and growth cones. © 2016 Anatomical Society.

Development of Postural Muscles and Their Innervation

PubMed Central

IJkema-Paassen, J.; Gramsbergen, A.

2005-01-01

Control of posture is a prerequisite for efficient motor performance. Posture depends on muscles capable of enduring contractions, whereas movements often require quick, forceful muscle actions. To serve these different goals, muscles contain fibers that meet these different tasks. Muscles with strong postural functions mainly consist of slow muscle fibers with a great resistance against fatigue. Flexor muscles in the leg and arm muscles are mainly composed of fast muscle fibers producing relatively large forces that are rapidly fatigable. Development of the neuromuscular system continues after birth. We discuss in the human baby and in animal experiments changes in muscle fiber properties, regression from polyneural into mononeural innervation, and developmental changes in the motoneurons of postural muscles during that period. The regression of poly-neural innervation in postural muscles and the development of dendrite bundles of their motoneurons seem to be linked to the transition from the immature into the adult-like patterns of moving and postural control. PMID:16097482

Reduced sympathetic innervation after alteration of target cell neurotransmitter phenotype in transgenic mice.

PubMed Central

Cho, S; Son, J H; Park, D H; Aoki, C; Song, X; Smith, G P; Joh, T H

1996-01-01

Neurotransmitters play a variety of important roles during nervous system development. In the present study, we hypothesized that neurotransmitter phenotype of both projecting and target cells is an important factor for the final synaptic linkage and its specificity. To test this hypothesis, we used transgenic techniques to convert serotonin/melatonin-producing cells of the pineal gland into cells that also produce dopamine and investigated the innervation of the phenotypically altered target cells. This phenotypic alteration markedly reduced the noradrenergic innervation originating from the superior cervical ganglia. Although the mechanism by which the reduction occurs is presently unknown, quantitative enzyme-linked immunoassay showed the presence of the equivalent amounts of nerve growth factor (NGF) in the control and transgenic pineal glands, suggesting that it occurred in a NGF-independent manner. The results suggest that target neurotransmitter phenotype influences the formation of afferent connections during development. Images Fig. 3 Fig. 4 PMID:8610132

Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

NASA Technical Reports Server (NTRS)

Misulis, K. E.; Dettbarn, W. D.

1985-01-01

An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

T1 Radiculopathy: Electrodiagnostic Evaluation

PubMed Central

Radecki, Jeffrey; Zimmer, Zachary R.

2008-01-01

Electromyography (EMG) studies are useful in the anatomical localization of nerve injuries and, in most cases, isolating lesions to a single nerve root level. Their utility is important in identifying specific nerve-root-level injuries where surgical or interventional procedures may be warranted. In this case report, an individual presented with right upper extremity radicular symptoms consistent with a clinical diagnosis of cervical radiculopathy. EMG studies revealed that the lesion could be more specifically isolated to the T1 nerve root and, furthermore, provided evidence that the abductor pollicis brevis receives predominantly T1 innervation. PMID:19083061

A quantitative study of skeletofusimotor innervation in the cat peroneus tertius muscle.

PubMed Central

Jami, L; Murthy, K S; Petit, J

1982-01-01

1. Physiological tests were used to identify skeletofusimotor or beta axons to the cat peroneus tertius muscle in order to assess the proportion of beta axons in the motor supply to this muscle. 2. Static beta axons (beta S) were identified by: (a) observation of a delay between the complete block of extrafusal contraction and the failure of spindle activation upon prolonged stimulation, (b) increase of spindle excitation with stimulation frequencies above that eliciting maximal extrafusal contraction, (c) observation of 'unfused' frequencygram of spindle primary afferent discharge during stimulation of the axon at frequencies above that eliciting complete fusion of extrafusal contraction and (d) static action exerted on the response of the spindle afferent to ramp stretch. 3. Dynamic beta axons (beta D) were identified by the persistence of spindle activation after selective block of extrafusal neuromuscular junctions and by their dynamic action on spindle primary endings. 4. The actions of 116 motor axons (conduction velocity 56-104 m/sec) on ninety-five spindle afferents (fifty-seven from primary and thirty-eight from secondary endings) were examined in ten experiments. Thirty-six beta axons (31% of the total sample) were identified: twenty-four beta S (conduction velocity 69-104 m/sec) and twelve beta D (conduction velocity 56-91 m/sec). 5. Twenty (35%) primary endings were activated by a beta S and sixteen (28%) by a beta D axon. Nineteen (45%) secondary endings were activated by a beta S and five (13%) by a beta D axon. Convergence of beta D and beta S axons on the same spindle occurred in 10% of instances. beta-innervated spindles were also supplied by gamma axons. 6. Most of the beta S motor units were of the fast-fatigue resistant (FR) type, with a few units of the fast-fatigable (FF) type, and nearly all the beta D motor units were of the slow (S) type. PMID:6213764

Innervation of the mammalian esophagus.

PubMed

Neuhuber, Winfried L; Raab, Marion; Berthoud, Hans-Rudolf; Wörl, Jürgen

2006-01-01

Understanding the innervation of the esophagus is a prerequisite for successful treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Although, at first glance, functions of the esophagus are relatively simple, their neuronal control is considerably complex. Vagal motor neurons of the nucleus ambiguus and preganglionic neurons of the dorsal motor nucleus innervate striated and smooth muscle, respectively. Myenteric neurons represent the interface between the dorsal motor nucleus and smooth muscle but they are also involved in striated muscle innervation. Intraganglionic laminar endings (IGLEs) represent mechanosensory vagal afferent terminals. They also establish intricate connections with enteric neurons. Afferent information is implemented by the swallowing central pattern generator in the brainstem, which generates and coordinates deglutitive activity in both striated and smooth esophageal muscle and orchestrates esophageal sphincters as well as gastric adaptive relaxation. Disturbed excitation/inhibition balance in the lower esophageal sphincter results in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents disrupts adaptation of deglutitive motor programs to bolus variables, eventually leading to megaesophagus. Both spinal and vagal afferents appear to contribute to painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons may be involved in intramural reflexes using acetylcholine, nitric oxide, substance P, CGRP and glutamate as main transmitters. In addition, other molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate these neuronal functions.

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

PubMed Central

Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

2016-01-01

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine.

PubMed

Vicentini, Geraldo E; Fracaro, Luciane; de Souza, Sara R G; Martins, Heber A; Guarnier, Flávia A; Zanoni, Jacqueline N

2016-01-01

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress.

The COP9 Signalosome Converts Temporal Hormone Signaling to Spatial Restriction on Neural Competence

PubMed Central

Huang, Yi-Chun; Lu, Yu-Nung; Wu, June-Tai; Chien, Cheng-Ting; Pi, Haiwei

2014-01-01

During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM. PMID:25393278

Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.

PubMed

Pai, Man-Hui; Ko, Tsui-Ling; Chou, Hsiu-Chu

2007-01-01

Some studies have documented taste changes in patients with diabetes mellitus (DM). In order to understand the relationships between taste disorders caused by DM and the innervation and morphologic changes in the taste buds, we studied the vallate papillae and their taste buds in rats with DM. DM was induced in these rats with streptozotocin (STZ), which causes the death of beta cells of the pancreas. The rats were sacrificed and the vallate papillae were dissected for morphometric and quantitative immunohistochemical analyses. The innervations of the vallate papillae and taste buds in diabetic and control rats were detected using immunohistochemistry employing antibodies directed against protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of diabetic vallate papillae, as well as taste cells in the taste buds, gradually decreased both intragemmally and intergemmally. The morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds per papilla (per animal). The quantification of innervation in taste buds of the diabetic rats supported the visual assessment of immunohistochemical labeling, that the innervation of taste cells was significantly reduced in diabetic animals. These findings suggest that taste impairment in diabetic subjects may be caused by neuropathy defects and/or morphological changes in the taste buds.

Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus

PubMed Central

Somogyi, Peter; Katona, Linda; Klausberger, Thomas; Lasztóczi, Bálint; Viney, Tim J.

2014-01-01

The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states. PMID:24366131

Involvement of transient receptor potential vanilloid 2 in intra-oral incisional pain.

PubMed

Urata, K; Shinoda, M; Ikutame, D; Iinuma, T; Iwata, K

2018-03-05

To examine whether transient receptor potential vanilloid 2 (TRPV2) contributes to the changes in intra-oral thermal and mechanical sensitivity following the incision of buccal mucosa. Buccal mucosal pain threshold was measured after the incision. Changes in the number of TRPV2-immunoreactive (IR) trigeminal ganglion (TG) neurons which innervate the whisker pad skin and buccal mucosa, changes in the number of isolectin B4-negative/isolectin B4-positive TRPV2-IR TG neurons which innervate the whisker pad skin and the buccal mucosa, and the effect of peripheral TRPV2 antagonism on the pain threshold of incisional whisker pad skin and buccal mucosa were examined after these injuries. Buccal mucosal pain hypersensitivities were induced on day 3 following the incision. The total number of TRPV2-IR TG neurons and the number of isolectin B4-negative TRPV2-IR TG neurons which innervate the whisker pad skin and buccal mucosa were increased. Buccal mucosal TRPV2 antagonism completely suppressed the heat and mechanical hypersensitivities, but not cold hypersensitivity. TRPV2 antagonist administration to the incisional whisker pad skin only partially suppressed pain hypersensitivities. The increased expression of TRPV2 in peptidergic TG neurons innervating the incisional buccal mucosa is predominantly involved in buccal mucosal heat hyperalgesia and mechanical allodynia following buccal mucosal incision. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

EGR-1 Expression in Catecholamine-synthesizing Neurons Reflects Auditory Learning and Correlates with Responses in Auditory Processing Areas.

PubMed

Dai, Jennifer B; Chen, Yining; Sakata, Jon T

2018-05-21

Distinguishing between familiar and unfamiliar individuals is an important task that shapes the expression of social behavior. As such, identifying the neural populations involved in processing and learning the sensory attributes of individuals is important for understanding mechanisms of behavior. Catecholamine-synthesizing neurons have been implicated in sensory processing, but relatively little is known about their contribution to auditory learning and processing across various vertebrate taxa. Here we investigated the extent to which immediate early gene expression in catecholaminergic circuitry reflects information about the familiarity of social signals and predicts immediate early gene expression in sensory processing areas in songbirds. We found that male zebra finches readily learned to differentiate between familiar and unfamiliar acoustic signals ('songs') and that playback of familiar songs led to fewer catecholaminergic neurons in the locus coeruleus (but not in the ventral tegmental area, substantia nigra, or periaqueductal gray) expressing the immediate early gene, EGR-1, than playback of unfamiliar songs. The pattern of EGR-1 expression in the locus coeruleus was similar to that observed in two auditory processing areas implicated in auditory learning and memory, namely the caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting a contribution of catecholamines to sensory processing. Consistent with this, the pattern of catecholaminergic innervation onto auditory neurons co-varied with the degree to which song playback affected the relative intensity of EGR-1 expression. Together, our data support the contention that catecholamines like norepinephrine contribute to social recognition and the processing of social information. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle

PubMed Central

Van Daele, Douglas J.; Cassell, Martin D.

2009-01-01

The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguous (NA) by 3 days post-inoculation., PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii (NTS), the Botzinger complex, and the parvocellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvocellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggest PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex central nervous system control over the multi-functional thyroarytenoid muscle.[297 words] PMID:19426785

A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation

PubMed Central

Nakano, Yukiko; Chayama, Kazuaki; Ochi, Hidenori; Toshishige, Masaaki; Hayashida, Yasufumi; Miki, Daiki; Hayes, C. Nelson; Suzuki, Hidekazu; Tokuyama, Takehito; Oda, Noboru; Suenari, Kazuyoshi; Uchimura-Makita, Yuko; Kajihara, Kenta; Sairaku, Akinori; Motoda, Chikaaki; Fujiwara, Mai; Watanabe, Yoshikazu; Yoshida, Yukihiko; Ohkubo, Kimie; Watanabe, Ichiro; Nogami, Akihiko; Hasegawa, Kanae; Watanabe, Hiroshi; Endo, Naoto; Aiba, Takeshi; Shimizu, Wataru; Ohno, Seiko; Horie, Minoru; Arihiro, Koji; Tashiro, Satoshi; Makita, Naomasa; Kihara, Yasuki

2013-01-01

Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67–5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA. PMID:23593010

Refinement of myotome values in the upper limb: Evidence from brachial plexus injuries.

PubMed

Bell, S W; Brown, M J C; Hems, T J

2017-02-01

We reviewed patients with partial supraclavicular brachial plexus injuries in order to refine the myotome values of the upper limb. Forty-two patients with defined partial injuries to the supraclavicular brachial plexus were reviewed from a prospective database. The injuries patterns covered C5, C5-6, C5-7, C5-8, C7-T1 and C8-T1 roots. Upper plexus injuries were classified on the basis of surgical exploration and intraoperative stimulation and lower plexus injuries from MRI. Flexor Carpi Radialis (FCR) was paralyzed in C5-7 injuries, in addition to paralysis of deltoid, supraspinatus, infraspinatus and biceps, when compared to C5-6 injuries. Complete paralysis of Flexor Digitorum Profundus (FDP) and Flexor Digitorum Superficialis (FDS) to all digits was identified in C7-T1 injuries. In C5-8 injuries weakness was noted in FDP of ulnar digits and intrinsics innervated by the ulnar nerve, while in C8-T1 injuries paralysis was noted in the FDP to the radial digits. All patients with C8-T1 injuries had paralysis of FDS and the thenar muscles. In upper plexus injuries paralysis of FCR indicated involvement of C7 root in addition to C5 and C6 roots. The results provide new detail of innervation of muscles acting on the hand. Flexor muscles and intrinsic muscles of the thumb and radial fingers (median nerve) have an important contribution from T1, while for those acting on the ulnar digits (ulnar nerve) the main contribution is from C8 with some input from C7. T1 also gives consistent innervation to extensor pollicis longus. A revised myotome chart for the upper limb is proposed. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Development of the nervous system in Phoronopsis harmeri (Lophotrochozoa, Phoronida) reveals both deuterostome- and trochozoan-like features

PubMed Central

2012-01-01

Background Inferences concerning the evolution of invertebrate nervous systems are often hampered by the lack of a solid data base for little known but phylogenetically crucial taxa. In order to contribute to the discussion concerning the ancestral neural pattern of the Lophotrochozoa (a major clade that includes a number of phyla that exhibit a ciliated larva in their life cycle), we investigated neurogenesis in Phoronopsis harmeri, a member of the poorly studied Phoronida, by using antibody staining against serotonin and FMRFamide in combination with confocal microscopy and 3D reconstruction software. Results The larva of Phoronopsis harmeri exhibits a highly complex nervous system, including an apical organ that consists of four different neural cell types, such as numerous serotonin-like immunoreactive flask-shaped cells. In addition, serotonin- and FMRFamide-like immunoreactive bi- or multipolar perikarya that give rise to a tentacular neurite bundle which innervates the postoral ciliated band are found. The preoral ciliated band is innervated by marginal serotonin-like as well as FMRFamide-like immunoreactive neurite bundles. The telotroch is innervated by two neurite bundles. The oral field is the most densely innervated area and contains ventral and ventro-lateral neurite bundles as well as several groups of perikarya. The digestive system is innervated by both serotonin- and FMRFamide-like immunoreactive neurites and perikarya. Importantly, older larvae of P. harmeri show a paired ventral neurite bundle with serial commissures and perikarya. Conclusions Serotonin-like flask-shaped cells such as the ones described herein for Phoronopsis harmeri are found in the majority of lophotrochozoan larvae and therefore most likely belong to the ground pattern of the last common lophotrochozoan ancestor. The finding of a transitory paired ventral neurite bundle with serially repeated commissures that disappears during metamorphosis suggests that such a structure was part of the “ur-phoronid” nervous system, but was lost in the adult stage, probably due to its acquired sessile benthic lifestyle. PMID:22827441

Differential effects of unilateral olfactory deprivation on noradrenergic and cholinergic systems in the main olfactory bulb of the rat.

PubMed

Gómez, C; Briñón, J G; Colado, M I; Orio, L; Vidal, M; Barbado, M V; Alonso, J R

2006-09-15

The lack of environmental olfactory stimulation produced by sensory deprivation causes significant changes in the deprived olfactory bulb. Olfactory transmission in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems. The present report examines the effects of unilateral deprivation on the noradrenergic and cholinergic centrifugal systems innervating the MOB. The morphology, distribution, and density of positive axons were studied in the MOBs of control and deprived rats, using dopamine-beta-hydroxylase (DBH)-immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial sections. Catecholamine content was compared among the different groups of MOBs (control, contralateral, and ipsilateral to the deprivation) using high-performance liquid chromatography analysis. Sensory deprivation revealed that the noradrenergic system developed adaptive plastic changes after olfactory deprivation, including important modifications in its fiber density and distribution, while no differences in cholinergic innervation were observed under the same conditions. The noradrenergic system underwent an important alteration in the glomerular layer, in which some glomeruli showed a dense noradrenergic innervation that was not detected in control animals. The DBH-positive glomeruli with the highest noradrenergic fiber density were compared with AChE-stained sections and it was observed that the strongly noradrenergic-innervated glomeruli were always atypical glomeruli (characterized by their strong degree of cholinergic innervation). In addition to the morphological findings, our biochemical data revealed that olfactory deprivation caused a decrease in the content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ipsilateral MOB in comparison to the contralateral and control MOBs, together with an increase in noradrenaline levels in both the ipsilateral and contralateral MOBs. Our results show that regulation of the noradrenergic centrifugal system in the MOB depends on environmental olfactory stimulation and that it is highly reactive to sensory deprivation. By contrast, the cholinergic system is fairly stable and does not exhibit clear changes after the loss of sensory inputs.

Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

PubMed

Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

2015-10-01

Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Anatomic evidence for peripheral neural processing in mammalian graviceptors

NASA Technical Reports Server (NTRS)

Ross, M. D.

1985-01-01

Ultrastructural study of utricular and saccular maculas demonstrates that their innervation patterns are complex. There is a clustering of type I and type II hair cells based upon a sharing of afferents, a system of efferent-type beaded fibers that is of intramacular (mostly calyceal) origin, and a plexus-like arrangement of afferents and efferents at many sites in the neuroepithelium. Results suggest that information concerning linear acceleration is processed peripherally, beginning at the hair cell level, before being sent to the central nervous system. The findings may supply a structural basis for peripheral adaptation to a constant stimulus, and for lateral inhibition to improve signal relative to noise.

Chemical activation of Wnt/β-catenin signalling inhibits innervation and causes skeletal tissue malformations during axolotl limb regeneration.

PubMed

Wischin, Sabina; Castañeda-Patlán, Cristina; Robles-Flores, Martha; Chimal-Monroy, Jesús

2017-04-01

Limb regeneration involves several interrelated physiological processes in which a particular signalling pathway may play a variety of functions. Blocking the function of Wnt/β-catenin signalling during limb regeneration inhibits regeneration in axolotls (Ambystoma mexicanum). Limb development shares many features with limb regeneration, and Wnt/β-catenin activation has different effects depending on the developmental stage. The aim of this study was to evaluate whether Wnt/β-catenin signalling activation during axolotl limb regeneration has different effects when activated at different stages of regeneration. To evaluate this hypothesis, we treated amputated axolotls with a Wnt agonist chemical at different stages of limb regeneration. The results showed that limb regeneration was inhibited when the treatment began before blastema formation. Under these conditions, blastema formation was hindered, possibly due to the lack of innervation. On the other hand, when axolotls were treated after blastema formation and immediately before the onset of morphogenesis, we observed structural disorganization in skeletal formation. In conclusion, we found that limb regeneration was differentially affected depending on the stage at which the Wnt signalling pathway was activated. Copyright © 2017 Elsevier B.V. All rights reserved.

Alteration of corneal epithelial ion transport by sympathectomy.

PubMed

Klyce, S D; Beuerman, R W; Crosson, C E

1985-04-01

The cornea is dually innervated, receiving afferent nerves from the trigeminal ganglion and efferent nerves from the superior cervical ganglion. This study examines the specific effects of superior cervical ganglionectomy (SCGX) on the in vitro ion transport characteristics of the rabbit corneal epithelium. Two weeks after SCGX, epithelial Cl--dependent transport and total ionic conductance were increased in comparison to values obtained in paired control eyes. This increased transport level appeared to be independent of membrane receptor activity as demonstrated by lack of responsiveness to alpha-adrenergic, beta-adrenergic, serotonergic, dopaminergic, nicotinic cholinergic, or muscarinic cholinergic blockade. Nevertheless, SCGX produced a supersensitivity to epinephrine-stimulated transport as measured by the responsiveness of the ion transport current. Furthermore, SCGX abolished the responsiveness of the epithelium to serotonin. On the basis of these and earlier findings, the authors conclude that corneal sympathetic innervation influences membrane and receptor properties. Autonomic neurotrophic effects in the corneal epithelium include suppression of apical membrane Cl- permeability and of beta-adrenoreceptor sensitivity to biogenic amines. It is proposed that the corneal serotonergic receptors that activate Cl- transport lie on the sympathetic nerve terminals and stimulate this transport process by causing the neural release of a catecholamine.

Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

PubMed

Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

2017-05-17

The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help modulate autonomic function. By contrast, the anterior cingulate cortex innervates other amygdalar parts, activating circuits to help avoid danger. Most IM neurons in primates label for the protein DARPP-32, known to be activated or inhibited based on the level of dopamine. Stress markedly increases dopamine release and inhibits IM neurons, compromises prefrontal control of the amygdala, and sets off a general alarm system as seen in affective disorders, such as chronic anxiety and post-traumatic stress disorder. Copyright © 2017 the authors 0270-6474/17/375051-14$15.00/0.

Reconstruction of totally degloved fingers: a novel application of the bilobed spiraled innervated radial artery superficial palmar branch perforator flap design provides for primary donor-site closure.

PubMed

Chi, Zhenglin; Yang, Peng; Song, Dajiang; Li, Zan; Tang, Liang; Gao, Weiyang; Song, Yonghuan; Chu, Tingang

2017-05-01

To investigate the results of resurfacing completely degloved digits using bilobed innervated radial artery superficial palmar branch (RASPB) perforator flap in a spiral fashion. A detailed anatomic study on 30 adult fresh frozen cadavers preinjected with silicone rubber compound to demarcate arterial anatomy documented locations, numbers, and diameters of arteries and skin perforators with surrounding nerves. The flap-raising procedure was performed using four fresh cadaver specimen. We reviewed the reconstruction of 12 digits by using a bilobed spiraled innervated RASPB free perforator flap after non-replantable degloving injury. Two skin paddles were marked out using standard points of reference. At least two separate cutaneous perforator vessels were identified using a hand-held Doppler and were dissected back to the RASPB in retrograde fashion. The skin paddles were then divided between the two cutaneous perforators to provide two separate paddles with a common vascular supply. The skin paddles were stacked in a spiral fashion on the flap inset, effectively increasing the width of the flap to cover the totally degloved finger while still allowing closure of the primary donor-site. The RASPB was present within the flap in all cadavers. The direct perforator and the musculocutaneous perforator were available in 93.33 and 76.67 %, respectively, with neither of them in 6.67 % of the cases. The constantly present two perforators allowed the design of a new bilobed spiraled innervated radial artery superficial palmar branch perforator flap. We used the proposed flap to reconstruct completely degloved digits in 12 patients (mean age 28.6 years; range 17-35 years). With our proposed flap, no flap failure or re-exploration occurred and the donor site was closed primarily in all cases. All the flaps survived uneventfully. Total active motion ranged from 92° to 140° and 111° to 155° in the cases with and without metacarpophalangeal joint involvement, respectively. The static 2 point discrimination test varied from 6 to 11 mm. All the patients were satisfied with the overall results. The bilobed flap is large enough to cover totally degloved finger defects and contain direct skin perforators, provides a bespoke cover for complex soft tissue defects of completely degloved digits while also improving morbidity and cosmesis of the donor site. Level IV, retrospective series.

The Trigeminal (V) and Facial (VII) Cranial Nerves

PubMed Central

Sanders, Richard D.

2010-01-01

There are close functional and anatomical relationships between cranial nerves V and VII in both their sensory and motor divisions. Sensation on the face is innervated by the trigeminal nerves (V) as are the muscles of mastication, but the muscles of facial expression are innervated mainly by the facial nerve (VII) as is the sensation of taste. This article briefly reviews the anatomy of these cranial nerves, disorders of these nerves that are of particular importance to psychiatry, and some considerations for differential diagnosis. PMID:20386632

Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

PubMed Central

Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

2015-01-01

Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

Characterisation of putative oxygen chemoreceptors in bowfin (Amia calva).

PubMed

Porteus, Cosima S; Wright, Patricia A; Milsom, William K

2014-04-15

Serotonin containing neuroepithelial cells (NECs) are putative oxygen sensing cells found in different locations within the gills of fish. In this study we wished to determine the effect of sustained internal (blood) hypoxaemia versus external (aquatic) hypoxia on the size and density of NECs in the first gill arch of bowfin (Amia calva), a facultative air breather. We identified five different populations of serotonergic NECs in this species (Types I-V) based on location, presence of synaptic vesicles (SV) that stain for the antibody SV2, innervation and labelling with the neural crest marker HNK-1. Cell Types I-III were innervated, and these cells, which participate in central O2 chemoreflexes, were studied further. Although there was no change in the density of any cell type in bowfin after exposure to sustained hypoxia (6.0 kPa for 7 days) without access to air, all three of these cell types increased in size. In contrast, only Type II and III cells increased in size in bowfin exposed to sustained hypoxia with access to air. These data support the suggestion that NECs are putative oxygen-sensing cells, that they occur in several locations, and that Type I cells monitor only hypoxaemia, whereas both other cell types monitor hypoxia and hypoxaemia.

Quantitative analysis of pre-and postsynaptic sex differences in the nucleus accumbens

PubMed Central

Forlano, Paul M.; Woolley, Catherine S.

2010-01-01

The nucleus accumbens (NAc) plays a central role in motivation and reward. While there is ample evidence for sex differences in addiction-related behaviors, little is known about the neuroanatomical substrates that underlie these sexual dimorphisms. We investigated sex differences in synaptic connectivity of the NAc by evaluating pre- and postsynaptic measures in gonadally intact male and proestrous female rats. We used DiI labeling and confocal microscopy to measure dendritic spine density, spine head size, dendritic length and branching of medium spiny neurons (MSNs) in the NAc, and quantitative immunofluorescence to measure glutamatergic innervation using pre- (vesicular glutamate transporter 1 and 2) and postsynaptic (post synaptic density 95) markers, as well as dopaminergic innervation of the NAc. We also utilized electron microscopy to complement the above measures. Clear but subtle sex differences were identified, namely in distal dendritic spine density and the proportion of large spines on MSNs, both of which are greater in females. Sex differences in spine density and spine head size are evident in both the core and shell subregions, but are stronger in the core. This study is the first demonstration of neuroanatomical sex differences in the NAc and provides evidence that structural differences in synaptic connectivity and glutamatergic input may contribute to behavioral sex differences in reward and addiction. PMID:20151363

Anatomical study of the opossum (Didelphis albiventris) extraocular muscles.

PubMed Central

Matheus, S M; Soares, J C; da Silva, A M; Seullner, G

1995-01-01

The anatomy of the extraocular muscles was studied in 10 adult opossums (Didelphis albiventris) of both sexes. Eight extraocular muscles were identified: 4 rectus muscles, 2 oblique muscles, the levator palpebrae superioris and the retractor ocular bulbi. The rectus muscles originate very close one to another between the orbital surfaces of the presphenoid and palatine bones. These muscles diverge on the way to their insertion which occurs at about 2 mm from the limbus. The levator palpebrae superioris originates with the dorsal rectus and is positioned dorsally in relation to it. The retractor ocular bulbi forms a cone which embraces the optic nerve and is located internally in relation to the rectus muscles. The dorsal oblique originates on the presphenoid bone and after a tendinous trajectory through a trochlea on the medial wall of the orbit, inserts into the ocular bulb. The only muscle arising from the anterior orbital floor is the ventral oblique. The main nerve supply for these muscles is the oculomotor, except for the dorsal oblique which is innervated by the trochlear nerve, and the lateral rectus which is innervated by the abducens nerve. The retractor ocular bulbi receives branches from the inferior division of the oculomotor nerve and some branches from the abducens nerve. Images Fig. 1 Fig. 2 Fig. 3 PMID:7649843

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

PubMed

Martino, G; Ivanenko, Y; Serrao, M; Ranavolo, A; Draicchio, F; Rinaldi, M; Casali, C; Lacquaniti, F

2018-03-01

A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Functional mapping of the pelvic floor and sphincter muscles from high-density surface EMG recordings.

PubMed

Peng, Yun; He, Jinbao; Khavari, Rose; Boone, Timothy B; Zhang, Yingchun

2016-11-01

Knowledge of the innervation of pelvic floor and sphincter muscles is of great importance to understanding the pathophysiology of female pelvic floor dysfunctions. This report presents our high-density intravaginal and intrarectal electromyography (EMG) probes and a comprehensive innervation zone (IZ) imaging technique based on high-density EMG readings to characterize the IZ distribution. Both intravaginal and intrarectal probes are covered with a high-density surface electromyography electrode grid (8 × 8). Surface EMG signals were acquired in ten healthy women performing maximum voluntary contractions of their pelvic floor. EMG decomposition was performed to separate motor-unit action potentials (MUAPs) and then localize their IZs. High-density surface EMG signals were successfully acquired over the vaginal and rectal surfaces. The propagation patterns of muscle activity were clearly visualized for multiple muscle groups of the pelvic floor and anal sphincter. During each contraction, up to 218 and 456 repetitions of motor units were detected by the vaginal and rectal probes, respectively. MUAPs were separated with their IZs identified at various orientations and depths. The proposed probes are capable of providing a comprehensive mapping of IZs of the pelvic floor and sphincter muscles. They can be employed as diagnostic and preventative tools in clinical practices.

Laser ablation of Drosophila embryonic motoneurons causes ectopic innervation of target muscle fibers

NASA Technical Reports Server (NTRS)

Chang, T. N.; Keshishian, H.

1996-01-01

We have tested the effects of neuromuscular denervation in Drosophila by laser-ablating the RP motoneurons in intact embryos before synaptogenesis. We examined the consequences of this ablation on local synaptic connectivity in both 1st and 3rd instar larvae. We find that the partial or complete loss of native innervation correlates with the appearance of alternate inputs from neighboring motor endings and axons. These collateral inputs are found at ectopic sites on the denervated target muscle fibers. The foreign motor endings are electrophysiologically functional and are observed on the denervated muscle fibers by the 1st instar larval stage. Our data are consistent with the existence of a local signal from the target environment, which is regulated by innervation and influences synaptic connectivity. Our results show that, despite the stereotypy of Drosophila neuromuscular connections, denervation can induce local changes in connectivity in wild-type Drosophila, suggesting that mechanisms of synaptic plasticity may also be involved in normal Drosophila neuromuscular development.

Brown adipose tissue macrophages control tissue innervation and homeostatic energy expenditure

PubMed Central

Cortese, Nina; Haimon, Zhana; Sar Shalom, Hadas; Kuperman, Yael; Kalchenko, Vyacheslav; Brandis, Alexander; David, Eyal; Segal-Hayoun, Yifat; Chappell-Maor, Louise; Yaron, Avraham; Jung, Steffen

2017-01-01

Tissue macrophages provide immune defense and contribute to establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator methyl-CpG binding protein 2 (Mecp2) in defined tissue macrophages. Animals lacking the Rett syndrome-associated gene in macrophages did not show signs of neurodevelopmental disorder, but displayed spontaneous obesity, which could be linked to impaired brown adipose tissue (BAT) function. Specifically, mutagenesis of a BAT-resident CX3CR1+ macrophage subpopulation compromised homeostatic, though not acute cold-induced thermogenesis. Mechanistically, BAT malfunction of pre-obese mice harboring mutant macrophages was associated with decreased sympathetic innervation and local norepinephrine titers, resulting in reduced adipocyte expression of thermogenic factors. Mutant macrophages over-expressed PlexinA4, which might contribute to the phenotype by repulsion of Sema6A-expressing sympathetic axons. Collectively, we report a previously unappreciated homeostatic role of macrophages in the control of tissue innervation, disruption of which in BAT results in metabolic imbalance. PMID:28459435

Densities of Serotonergic Projections as Revealed by In Situ Synthesised Labelled α-Methyl-Serotonin: an Autoradiographic Evaluation

PubMed Central

Nishi, Kyoko; Takahashi, Sho

2013-01-01

An estimate of serotonergic innervation density and regional serotonin (5-HT) concentration was performed from the distribution of in situ produced labelled α-methyl-serotonin. Rats were injected with (3H) labelled α-methyl-L-tryptophan and the tracer distribution was measured using the autoradiographic method 14 days following the injection. In a separate experiment, the total brain concentration of 5-HT in the rat brain was found to be 2.4 ± 0.2 nmol/g. Based on this, and the assumption that the specific activity of in situ produced α-methyl-serotonin is the same as that of the injected tracer, it was possible to estimate the regional concentrations of 5-HT and the relative concentration of regional serotonergic innervations. It was found, and reported for the first time here, that the highest concentration of serotonergic innervation is present in the solitary nucleus. Regionally measured 5-HT concentrations accord well with previously reported concentrations of 5-HT. PMID:21472458

Olfactory projection neuron pathways in two species of marine Isopoda (Peracarida, Malacostraca, Crustacea).

PubMed

Stemme, Torben; Eickhoff, René; Bicker, Gerd

2014-08-01

The neuroanatomy of the olfactory pathway has been intensely studied in many representatives of Malacostraca. Nevertheless, the knowledge about bilateral olfactory integration pathways is mainly based on Decapoda. Here, we investigated the olfactory projection neuron pathway of two marine isopod species, Saduria entomon and Idotea emarginata, by lipophilic dye injections into the olfactory neuropil. We show that both arms of the olfactory globular tract form a chiasm in the center of the brain, as known from several other crustaceans. Furthermore, the olfactory projection neurons innervate both the medulla terminalis and the hemiellipsoid body of the ipsi- and the contralateral hemisphere. Both protocerebral neuropils are innervated to a comparable extent. This is reminiscent of the situation in the basal decapod taxon Dendrobranchiata. Thus, we propose that an innervation by the olfactory globular tract of both the medulla terminalis and the hemiellipsoid body is characteristic of the decapod ground pattern, but also of the ground pattern of Caridoida. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Multifactorial role of Peripheral Nervous System in Bone Growth

NASA Astrophysics Data System (ADS)

Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

2017-09-01

Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

PubMed Central

Pujol, Remy; Cunningham, Dale E.; Hailey, Dale W.; Prendergast, Andrew; Rubel, Edwin W.; Raible, David W.

2016-01-01

ABSTRACT Failure to form proper synapses in mechanosensory hair cells, the sensory cells responsible for hearing and balance, leads to deafness and balance disorders. Ribbons are electron-dense structures that tether synaptic vesicles to the presynaptic zone of mechanosensory hair cells where they are juxtaposed with the post-synaptic endings of afferent fibers. They are initially formed throughout the cytoplasm, and, as cells mature, ribbons translocate to the basolateral membrane of hair cells to form functional synapses. We have examined the effect of post-synaptic elements on ribbon formation and maintenance in the zebrafish lateral line system by observing mutants that lack hair cell innervation, wild-type larvae whose nerves have been transected and ribbons in regenerating hair cells. Our results demonstrate that innervation is not required for initial ribbon formation but suggest that it is crucial for regulating the number, size and localization of ribbons in maturing hair cells, and for ribbon maintenance at the mature synapse. PMID:27103160

Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells.

PubMed

Suli, Arminda; Pujol, Remy; Cunningham, Dale E; Hailey, Dale W; Prendergast, Andrew; Rubel, Edwin W; Raible, David W

2016-06-01

Failure to form proper synapses in mechanosensory hair cells, the sensory cells responsible for hearing and balance, leads to deafness and balance disorders. Ribbons are electron-dense structures that tether synaptic vesicles to the presynaptic zone of mechanosensory hair cells where they are juxtaposed with the post-synaptic endings of afferent fibers. They are initially formed throughout the cytoplasm, and, as cells mature, ribbons translocate to the basolateral membrane of hair cells to form functional synapses. We have examined the effect of post-synaptic elements on ribbon formation and maintenance in the zebrafish lateral line system by observing mutants that lack hair cell innervation, wild-type larvae whose nerves have been transected and ribbons in regenerating hair cells. Our results demonstrate that innervation is not required for initial ribbon formation but suggest that it is crucial for regulating the number, size and localization of ribbons in maturing hair cells, and for ribbon maintenance at the mature synapse. © 2016. Published by The Company of Biologists Ltd.

Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice

PubMed Central

Reznikov, Leah R.; Meyerholz, David K.; Adam, Ryan J.; Abou Alaiwa, Mahmoud; Jaffer, Omar; Michalski, Andrew S.; Powers, Linda S.; Price, Margaret P.; Stoltz, David A.; Welsh, Michael J.

2016-01-01

Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma. PMID:27820848

Unilateral severe chronic periodontitis associated with ipsilateral surgical resection of cranial nerves V, VI, and VII.

PubMed

Zavarella, Matthew M; Leblebicioglu, Binnaz; Claman, Lewis J; Tatakis, Dimitris N

2006-01-01

The central and peripheral nervous systems participate in several local physiological and pathological processes. There is experimental evidence that the inflammatory, local immune, and wound healing responses of a tissue can be modulated by its innervation. The aim of this clinical report is to present a case of unilateral severe periodontitis associated with ipsilateral surgical resection of the fifth, sixth, and seventh cranial nerves and to discuss the possible contribution of the nervous system to periodontal pathogenesis. A 39-year-old female patient with a history of a cerebrovascular accident caused by a right pontine arteriovenous malformation and destruction of the right fifth, sixth, and seventh cranial nerves was diagnosed with severe chronic periodontitis affecting only the right maxillary and mandibular quadrants. The patient's oral hygiene was similar for right and left sides of the mouth. Percentages of tooth surfaces carrying dental plaque were 41% and 36% for right and left sides, respectively. Non-surgical and surgical periodontal therapy was performed, and the patient was placed on a regular periodontal maintenance schedule. Healing following initial periodontal therapy and osseous periodontal surgery occurred without complications. Follow-up clinical findings at 1 year revealed stable periodontal health. This case report suggests that periodontal innervation may contribute to the regulation of local processes involved in periodontitis pathogenesis. It also suggests that periodontal therapy can be performed successfully at sites and in patients affected by paralysis.

Autonomic control of the eye

PubMed Central

McDougal, David H.; Gamlin, Paul D.

2016-01-01

The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia. PMID:25589275

Evoked electromyography to rocuronium in orbicularis oris and gastrocnemius in facial nerve injury in rabbits.

PubMed

Xing, Yian; Chen, Lianhua; Li, Shitong

2013-11-01

Muscles innervated by the facial nerve show different sensitivities to muscle relaxants than muscles innervated by somatic nerves, especially in the presence of facial nerve injury. We compared the evoked electromyography (EEMG) response of orbicularis oris and gastrocnemius in with and without a non-depolarizing muscle relaxant in a rabbit model of graded facial nerve injury. Differences in EEMG response and inhibition by rocuronium were measured in the orbicularis oris and gastrocnemius muscles 7 to 42 d after different levels of facial nerve crush injuries in adult rabbits. Baseline EEMG of orbicularis oris was significantly smaller than those of the gastrocnemius. Gastrocnemius was more sensitive to rocuronium than the facial muscles (P < 0.05). Baseline EEMG and EEMG amplitude of orbicularis oris in the presence of rocuronium was negatively correlated with the magnitude of facial nerve injury but the sensitivity to rocuronium was not. No significant difference was found in the onset time and the recovery time of rocuronium among gastrocnemius and normal or damaged facial muscles. Muscles innervated by somatic nerves are more sensitive to rocuronium than those innervated by the facial nerve, but while facial nerve injury reduced EEMG responses, the sensitivity to rocuronium is not altered. Partial neuromuscular blockade may be a suitable technique for conducting anesthesia and surgery safely when EEMG monitoring is needed to preserve and protect the facial nerve. Additional caution should be used if there is a risk of preexisting facial nerve injury. Copyright © 2013 Elsevier Inc. All rights reserved.

Physiology of Normal Esophageal Motility

PubMed Central

Goyal, Raj K; Chaudhury, Arun

2009-01-01

The esophagus consists of two different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consist of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure due to its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. PMID:18364578

Target innervation is necessary for neuronal polyploidization in the terrestrial slug Limax.

PubMed

Matsuo, Ryota; Yamagishi, Miki; Wakiya, Kyoko; Tanaka, Yoko; Ito, Etsuro

2013-08-01

The brain of gastropod mollusks contains many giant neurons with polyploid genomic DNAs. Such DNAs are generated through repeated DNA endoreplication during body growth. However, it is not known what triggers DNA endoreplication in neurons. There are two possibilities: (1) DNAs are replicated in response to some unknown molecules in the hemolymph that reflect the nutritive status of the animal; or (2) DNAs are replicated in response to some unknown factors that are retrogradely transported through axons from the innervated target organs. We first tested whether hemolymph with rich nutrition could induce DNA endoreplication. We tested whether the transplanted brain exhibits enhanced DNA endoreplication like an endogenous brain does when transplanted into the homocoel of the body of a slug whose body growth is promoted by an increased food supply. However, no enhancement was observed in the frequency of DNA endoreplication when we compared the transplanted brains in the growth-promoted and growth-suppressed host slugs, suggesting that the humoral environment is irrelevant to triggering the body growth-dependent DNA endoreplication. Next, we tested the requirement of target innervation by surgically dissecting a unilateral posterior pedal nerve of an endogenous brain. Substantially lower number of neurons exhibited DNA endoreplication in the pedal ganglion ipsilateral to the dissected nerve. These results support the view that enhanced DNA endoreplication is mediated by target innervation and is not brought about through the direct effect of humoral factors in the hemolymph during body growth. Copyright © 2013 Wiley Periodicals, Inc.

Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings

PubMed Central

2016-01-01

Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or “edge,” due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. PMID:26823515

Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings.

PubMed

Brown, M Christian

2016-03-01

Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or "edge," due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. Copyright © 2016 the American Physiological Society.

Synaptic Inputs Compete during Rapid Formation of the Calyx of Held: A New Model System for Neural Development

PubMed Central

Holcomb, Paul S.; Hoffpauir, Brian K.; Hoyson, Mitchell C.; Jackson, Dakota R.; Deerinck, Thomas J.; Marrs, Glenn S.; Dehoff, Marlin; Wu, Jonathan; Ellisman, Mark H.

2013-01-01

Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics. To investigate CH development, we made the first application of serial block-face scanning electron microscopy to neural development with fine temporal resolution and thereby accomplished the first time series for 3D ultrastructural analysis of neural circuit formation. This approach revealed a growth spurt of added apposed surface area (ASA) >200 μm2/d centered on a single age at postnatal day 3 in mice and an initial rapid phase of growth and competition that resolved to monoinnervation in two-thirds of cells within 3 d. This rapid growth occurred in parallel with an increase in action potential threshold, which may mediate selection of the strongest input as the winning competitor. ASAs of competing inputs were segregated on the cell body surface. These data suggest mechanisms to select “winning” inputs by regional reinforcement of postsynaptic membrane to mediate size and strength of competing synaptic inputs. PMID:23926251

Age-related changes in functional NANC innervation with VIP and substance P in the jejunum of Lewis rats.

PubMed

Kasparek, Michael S; Fatima, Javairiah; Iqbal, Corey W; Duenes, Judith A; Sarr, Michael G

2009-12-03

Age-related changes in non-adrenergic, non-cholinergic (NANC) neurotransmission might contribute to differences in gastrointestinal motility. Our aim was to determine age-related changes in functional innervation with vasoactive intestinal polypeptide (VIP) and substance P (Sub P) in rat jejunum. We hypothesized that maturation causes changes in neurotransmission with these two neuropeptides. Longitudinal and circular jejunal muscle strips from young (3 months) and middle-aged (15 months) rats (total: 24 rats) were studied; the response to exogenous VIP and Sub P and the effect of their endogenous release from the enteric nervous system during electrical field stimulation (EFS) were evaluated. In longitudinal muscle, response to exogenous VIP and endogenously released VIP during EFS were increased in middle-aged rats, while the effect of endogenously released Sub P was decreased. In the circular muscle, the response to endogenously released VIP was increased in middle-aged rats, while the effects of exogenous VIP and endogenously released Sub P were unchanged. Response to exogenous Sub P was unaffected by maturation in both muscle layers. Spontaneous contractile activity was increased in the longitudinal and circular muscle of the older rats. In the jejunum of middle-aged rats, participation of VIP in functional NANC innervation was increased, while functional innervation with Sub P was decreased. These changes in the balance of inhibitory and excitatory neurotransmission occur during the year of maturation in rats and demonstrate an age-dependant plasticity of neuromuscular bowel function.

Effects of amyloid-β plaque proximity on the axon initial segment of pyramidal cells.

PubMed

León-Espinosa, Gonzalo; DeFelipe, Javier; Muñoz, Alberto

2012-01-01

The output of cortical pyramidal cells reflects the balance between excitatory inputs of cortical and subcortical origin, and inhibitory inputs from distinct populations of cortical GABAergic interneurons, each of which selectively innervate different domains of neuronal pyramidal cells (i.e., dendrites, soma and axon initial segment [AIS]). In Alzheimer's disease (AD), the presence of amyloid-β (Aβ) plaques alters the synaptic input to pyramidal cells in a number of ways. However, the effects of Aβ plaques on the AIS have still not been investigated to date. This neuronal domain is involved in input integration, as well as action potential initiation and propagation, and it exhibits Ca2+- and activity-dependent structural plasticity. The AIS is innervated by GABAergic axon terminals from chandelier cells, which are thought to exert a strong influence on pyramidal cell output. In the AβPP/PS1 transgenic mouse model of AD, we have investigated the effects of Aβ plaques on the morphological and neurochemical features of the AIS, including the cisternal organelle, using immunocytochemistry and confocal microscopy, as well as studying the innervation of the AIS by chandelier cell axon terminals. There is a strong reduction in GABAergic terminals that appose AIS membrane surfaces that are in contact with Aβ plaques, indicating altered inhibitory synapsis at the AIS. Thus, despite a lack of gross structural alterations in the AIS, this decrease in GABAergic innervation may deregulate AIS activity and contribute to the hyperactivity of neurons in contact with Aβ plaques.

A novel mechanism of bradycardia and the character of acetylcholine in the heart.

PubMed

Młynarska, M S; Garlicki, M; Jakobczak, M M; Skowron-Cendrzak, A

2006-01-01

At first the aim of our study was to observe the simultaneous responses of two hearts after intraarterial (into a. femoralis) adrenaline administration, in the rat with its own heart and a transplanted one--hence non-innervated. After these, some next experiments were performed: in some rats the His bundle of the heterotopically transplanted heart was damaged before transplantation. In all experiments the heart rate was observed on ECG and simultaneously, the arterial blood pressure was recorded from femoral artery in Vetbutal-anaesthetized rats. 1) both the heterotopically transplanted, non-innervated heart and the animal's own heart reacted to adrenaline administeration by producing bradycardia, 2) the heterotopically transplanted heart with the damaged His bundle--hence with a ventricular block reacted to adrenaline administration by raising the heart rate, whereas at the same time and in the same animal its own heart reacted by producing bradycardia. 1) the cause of bradycardia after adrenaline administration does not lie in the reflex from the arcus aortae, since we observed bradycardia after adrenaline administration also in the transplanted, non-innervated heart; therefore the baroreceptor reflex is not the cause of bradycardia after adrenaline administration; 2) bradycardia after adrenaline occurs in both the proper heart and the transplanted, non-innervated one, as a result of an interaction between two cholinergic centres which must be situated above and below the point of the His bundle interruption. The role of acetylcholine in the heart results from the interaction between these two centres.

The basilar pontine nuclei and the nucleus reticularis tegmenti pontis subserve distinct cerebrocerebellar pathways.

PubMed

Cicirata, Federico; Serapide, Maria Francesca; Parenti, Rosalba; Pantò, Maria Rosita; Zappalà, Agata; Nicotra, Annalisa; Cicero, Deborah

2005-01-01

Previous studies often considered the basilar pontine nuclei (BPN) and the nucleus reticularis tegmenti pontis (NRTP) as relays of a single cerebro-(ponto)-cerebellar pathway. Conversely, the different cortical afferences to the BPN and the NRTP, as well as the anatomical and functional features of the cerebellopetal projections from these pontine nuclei, support the different, and for some aspect, complementary arrangement of the cerebrocerebellar pathways relayed by the BPN or NRTP. Both the BPN and the NRTP are innervated from the cerebral cortex, but with regional prevalence. The NRTP is principally innervated from motor or sensori-motor areas while the BPN are principally innervated from sensory, mainly teloceptive, and associative area. Projections from sensory-motor areas were also traced to the BPN. The BPN and NRTP project to all parts of the cerebellar cortex with a similar pattern. In fact, from single areas of them projections were traced to set of sagittal stripes of the cerebellar cortex. In variance to such analogies, the projections to the cerebellar nuclei differed between those traced from the NRTP and from BPN. In fact, BPN and NRTP have private terminal areas in the cerebellar nuclei with relatively little overlaps. The BPN innervated the lateroventral part of the nucleus lateralis and the caudoventral aspect of the nucleus interpositalis posterioris. The NRTP principally innervated the mediodorsal part of the nucleus lateralis, the nucleus interpositalis anterioris, the nucleus medialis. Since the single cerebellar nuclei have their specific targets in the extracerebellar brain areas, it follows that the BPN and the NRTP, passing through their cerebellar nuclei relays, are devoted to control different brain areas and thus likely to play different functional roles. From single pontine regions (of both BPN and NRTP) projections were traced to the cerebellar cortex and to the cerebellar nuclei. In some cases these projections reached areas which are likely anatomically connected (by Purkinje axons). This pattern of the pontine projections was termed as coupled projection. In some other cases, the projections reached areas of the cerebellar cortex but not the nuclear regions innervated by them. We termed this as uncoupled projection. The existence of both coupled and uncoupled projections, open new vistas on the functional architecture of the pontocerebellar pathway. More in detail, this study showed the different quantitative and topographic distribution of the coupled and uncoupled projections visualized in the cerebellar projections from BPN and NRTP. All these evidences strongly support the anatomical and the functional differences that characterise the cerebrocerebellar pathways relayed by the BPN and the NRTP.

Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

PubMed Central

Li, Jie

2017-01-01

It is well established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared with skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared with pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn neurons process sensory input from muscle versus skin at the synaptic level. Using a novel ex vivo spinal cord preparation, here we identify the functional organization of muscle and cutaneous afferent synapses onto immature rat lamina I spino-parabrachial neurons, which serve as a major source of nociceptive transmission to the brain. Stimulation of the gastrocnemius nerve and sural nerve revealed significant convergence of muscle and cutaneous afferent synaptic input onto individual projection neurons. Muscle afferents displayed a higher probability of glutamate release, although short-term synaptic plasticity was similar between the groups. Importantly, muscle afferent synapses exhibited greater relative expression of Ca2+-permeable AMPARs compared with cutaneous inputs. In addition, the prevalence and magnitude of spike timing-dependent long-term potentiation were significantly higher at muscle afferent synapses, where it required Ca2+-permeable AMPAR activation. Collectively, these results provide the first evidence for afferent-specific properties of glutamatergic transmission within the superficial dorsal horn. A larger propensity for activity-dependent strengthening at muscle afferent synapses onto developing spinal projection neurons could contribute to the enhanced ability of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain in children following injury. SIGNIFICANCE STATEMENT The neurobiological mechanisms underlying the high prevalence of chronic musculoskeletal pain remain poorly understood, in part because little is known about why sensory neurons innervating muscle appear more capable of sensitizing nociceptive pathways in the CNS compared with skin afferents. The present study identifies, for the first time, the functional properties of muscle and cutaneous afferent synapses onto immature lamina I projection neurons, which convey nociceptive information to the brain. Despite many similarities, an enhanced relative expression of Ca2+-permeable AMPA receptors at muscle afferent synapses drives greater LTP following repetitive stimulation. A preferential ability of the dorsal horn synaptic network to amplify nociceptive input arising from muscle is predicted to favor the generation of musculoskeletal pain following injury. PMID:28069928

Detection of Multiple Innervation Zones from Multi-Channel Surface EMG Recordings with Low Signal-to-Noise Ratio Using Graph-Cut Segmentation.

PubMed

Marateb, Hamid Reza; Farahi, Morteza; Rojas, Monica; Mañanas, Miguel Angel; Farina, Dario

2016-01-01

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies.

Detection of Multiple Innervation Zones from Multi-Channel Surface EMG Recordings with Low Signal-to-Noise Ratio Using Graph-Cut Segmentation

PubMed Central

Farahi, Morteza; Rojas, Monica; Mañanas, Miguel Angel; Farina, Dario

2016-01-01

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies. PMID:27978535

Mild closed head injury promotes a selective trigeminal hypernociception: implications for the acute emergence of post-traumatic headache.

PubMed

Benromano, T; Defrin, R; Ahn, A H; Zhao, J; Pick, C G; Levy, D

2015-05-01

Headache is one of the most common symptoms following traumatic head injury. The mechanisms underlying the emergence of such post-traumatic headache (PTH) remain unknown but may be related to injury of deep cranial tissues or damage to central pain processing pathways, as a result of brain injury. A mild closed head injury in mice combined with the administration of cranial or hindpaw formalin tests was used to examine post-traumatic changes in the nociceptive processing from deep cranial tissues or the hindpaw. Histological analysis was used to examine post-traumatic pro-inflammatory changes in the calvarial periosteum, a deep cranial tissue. At 48 h after head injury, mice demonstrated enhanced nociceptive responses following injection of formalin into the calvarial periosteum, a deep cranial tissue, but no facilitation of the nociceptive responses following injection of formalin into an extracranial tissue, the hindpaw. Mice also showed an increase in the number of activated periosteal mast cells 48 h following mild head trauma, suggesting an inflammatory response. Our study demonstrates that mild closed head injury is associated with enhanced processing of nociceptive information emanating from trigeminal-innervated deep cranial tissues, but not from non-cranial tissues. Based on these finding as well as the demonstration of head injury-evoked degranulation of calvarial periosteal mast cells, we propose that inflammatory-evoked enhancement of peripheral cranial nociception, rather than changes in supraspinal pain mechanisms play a role in the initial emergence of PTH. Peripheral targeting of nociceptors that innervate the calvaria may be used to ameliorate PTH pain. © 2014 European Pain Federation - EFIC®

A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection in the Drosophila neuromuscular system

PubMed Central

Kurusu, Mitsuhiko; Cording, Amy; Taniguchi, Misako; Menon, Kaushiki; Suzuki, Emiko; Zinn, Kai

2008-01-01

Summary In Drosophila embryos and larvae, a small number of identified motor neurons innervate body wall muscles in a highly stereotyped pattern. Although genetic screens have identified many proteins that are required for axon guidance and synaptogenesis in this system, little is known about the mechanisms by which muscle fibers are defined as targets for specific motor axons. To identify potential target labels, we screened 410 genes encoding cell-surface and secreted proteins, searching for those whose overexpression on all muscle fibers causes motor axons to make targeting errors. Thirty such genes were identified, and a number of these were members of a large gene family encoding proteins whose extracellular domains contain leucine-rich repeat (LRR) sequences, which are protein interaction modules. By manipulating gene expression in muscle 12, we showed that four LRR proteins participate in the selection of this muscle as the appropriate synaptic target for the RP5 motor neuron. PMID:18817735

Identification of neuroanatomic circuits from spinal cord to stomach in mouse: retrograde transneuronal viral tracing study.

PubMed

Ye, Da-Wei; Liu, Cheng; Tian, Xue-Bi; Xiang, Hong-Bing

2014-01-01

To determine the spinal innervation and neuronal connections is important for studying gastric carbohydrate metabolism and motor responses. Neurons involved in the efferent control of the stomach were identified following visualization of pseudorabies virus (PRV)-614 retrograde tracing. PRV-614 was injected into the ventral stomach wall in 13 adult C57BL/6J strain male mice. On the fifth day postinjection, animals were humanely sacrificed, and spinal cords were removed and sectioned, and processed for PRV visualization. The virus injected into the ventral stomach wall was specifically transported to the thoracic spinal cord. At 5 d after injection of the PRV-614, stomach enlargement and tissue edema were found, and PRV-614 positive cells were found in the intermediolateral cell column, the intercalates nucleus or the central autonomic nucleus of spinal cord segments T3 to L1, and major PRV-614 labeled cells were focused in the T6-10 segment. Our results revealed neuroanatomical circuits between stomach and the spinal intermediolateral cell column neurons.

Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment?

PubMed Central

Bowirrat, Abdalla; Chen, Thomas JH; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda LH; Bailey, John A.; Braverman, Eric R.; Kerner, Mallory; Giordano, John; Morse, Siohban; Downs, B. William; Waite, Roger L.; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

2013-01-01

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest examination of multifactorial interactions of an individual’s genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission. PMID:22371275

The stimulus selectivity and connectivity of layer six principal cells reveals cortical microcircuits underlying visual processing.

PubMed

Vélez-Fort, Mateo; Rousseau, Charly V; Niedworok, Christian J; Wickersham, Ian R; Rancz, Ede A; Brown, Alexander P Y; Strom, Molly; Margrie, Troy W

2014-09-17

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Neuropsychopharmacology and neurogenetic aspects of executive functioning: should reward gene polymorphisms constitute a diagnostic tool to identify individuals at risk for impaired judgment?

PubMed

Bowirrat, Abdalla; Chen, Thomas J H; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda Lh; Bailey, John A; Braverman, Eric R; Kerner, Mallory; Giordano, John; Morse, Siobhan; Downs, B William; Waite, Roger L; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

2012-04-01

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

PubMed Central

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors. PMID:28066196

Modulatory Role of Sensory Innervation on Hair Follicle Stem Cell Progeny during Wound Healing of the Rat Skin

PubMed Central

Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I.; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

2012-01-01

Background The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. Methodology/Principal Findings We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU+) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU+ nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU+/CldU+). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU+/CldU+ cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34+ and BrdU-retaining cells of the hair follicles. Conclusions/Significance Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing. PMID:22574159

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

PubMed

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

The Changing Roles of Neurons in the Cortical Subplate

PubMed Central

Friedlander, Michael J.; Torres-Reveron, Juan

2009-01-01

Neurons may serve different functions over the course of an organism's life. Recent evidence suggests that cortical subplate (SP) neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the SP. While the cortical plate neurons form most of the cortical layers (layers 2–6), the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10–20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving SP cells' axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of these cells at different stages of development. PMID:19688111

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

PubMed

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors.

Modulatory role of sensory innervation on hair follicle stem cell progeny during wound healing of the rat skin.

PubMed

Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

2012-01-01

The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles. Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing.

Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit.

PubMed

Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R

2011-08-03

The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

PubMed

Meneray, M A; Bennett, D J; Nguyen, D H; Beuerman, R W

1998-01-01

This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the acinar appearance or secretory responsiveness of the gland. Loss of the considerable sensory innervation from the trigeminal ganglion has pronounced effects on the pharmacologic responsiveness and the structure of the lacrimal gland. The effects of sensory innervation on the gland may be mediated through two possible pathways: direct input to the gland or control of the preganglionic parasympathetic pathway.

Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis

PubMed Central

Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

2015-01-01

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (P<0.001) and deep infiltrating endometriotic lesions of uterosacral ligament (P = 0.028)compared with glandular epithelial cells of the endometrium from women with endometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (P<0.001, P<0.001, respectively). NFDs of Anti-TH (+) endometriosis-associated sympathetic nerve of peritoneal endometriosis (p<0.001) and deep endometriosis of uterosacral ligament (p<0.001) were significantly lower than NFDs of para-endometriotic sympathetic nerve. Our results suggest that Sema 3A may contribute to the regulation of aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. PMID:26720585

Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

PubMed

Seidler, Frederic J; Slotkin, Theodore A

2011-05-30

Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

Crossed motor innervation of the base of human tongue

PubMed Central

Jordan, Amy S.; Nicholas, Christian L.; Cori, Jennifer M.; Semmler, John G.; Trinder, John

2015-01-01

Muscle fibers of the genioglossus (GG) form the bulk of the muscle mass at the base of the tongue. The motor control of the tongue is critical for vocalization, feeding, and breathing. Our goal was to assess the patterns of motor innervation of GG single motor units (SMUs) in humans. Simultaneous monopolar recordings were obtained from four sites in the base of the tongue bilaterally at two antero-posterior levels from 16 resting, awake, healthy adult males, who wore a face mask with airway pressure and airflow sensors. We analyzed 69 data segments in which at least one lead contained large action potentials generated by an SMU. Such potentials served as triggers for spike-triggered averaging (STA) of signals recorded from the other three sites. Spontaneous activity of the SMUs was classified as inspiratory modulated, expiratory modulated, or tonic. Consistent with the antero-posterior orientation of GG fibers, 44 STAs (77%) recorded ipsilateral to the trigger yielded sharp action potentials with a median amplitude of 52 μV [interquartile range (IQR): 25–190] that were time shifted relative to the trigger by about 1 ms. Notably, 48% of recordings on the side opposite to the trigger also yielded sharp action potentials. Of those, 17 (29%) had a median amplitude of 63 μV (IQR: 39–96), and most were generated by tonic SMUs. Thus a considerable proportion of GG muscle fibers receive a crossed motor innervation. Crossed innervation may help ensure symmetry and stability of tongue position and movements under normal conditions and following injury or degenerative changes affecting the tongue. PMID:25855691

Target innervation is necessary for neuronal polyploidization in the terrestrial slug Limax.

PubMed

Matsuo, Ryota; Yamagishi, Miki; Wakiya, Kyoko; Tanaka, Yoko; Ito, Etsuro

2013-05-30

The brain of gastropod mollusks contains many giant neurons with polyploid genomic DNAs. Such DNAs are generated through repeated DNA endoreplication during body growth. However, it is not known what triggers DNA endoreplication in neurons. There are two possibilities: (1) DNAs are replicated in response to some unknown molecules in the hemolymph that reflect the nutritive status of the animal; or (2) DNAs are replicated in response to some unknown factors that are retrogradely transported through axons from the innervated target organs. We first tested whether hemolymph with rich nutrition could induce DNA endoreplication. We tested whether the transplanted brain exhibits enhanced DNA endoreplication like an endogenous brain does when transplanted into the homocoel of the body of a slug whose body growth is promoted by an increased food supply. However, no enhancement was observed in the frequency of DNA endoreplication when we compared the transplanted brains in the growth-promoted and growth-suppressed host slugs, suggesting that the humoral environment is irrelevant to triggering the body growth-dependent DNA endoreplication. Next, we tested the requirement of target innervation by surgically dissecting a unilateral posterior pedal nerve of an endogenous brain. Substantially lower number of neurons exhibited DNA endoreplication in the pedal ganglion ipsilateral to the dissected nerve. These results support the view that enhanced DNA endoreplication is mediated by target innervation and is not brought about through the direct effect of humoral factors in the hemolymph during body growth. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013. Copyright © 2013 Wiley Periodicals, Inc.

Deletion of Tsc2 in Nociceptors Reduces Target Innervation, Ion Channel Expression, and Sensitivity to Heat

PubMed Central

Carlin, Dan; Golden, Judith P.; Monk, Kelly R.

2018-01-01

Abstract The mechanistic target of rapamycin complex 1 (mTORC1) is known to regulate cellular growth pathways, and its genetic activation is sufficient to enhance regenerative axon growth following injury to the central or peripheral nervous systems. However, excess mTORC1 activation may promote innervation defects, and mTORC1 activity mediates injury-induced hypersensitivity, reducing enthusiasm for the pathway as a therapeutic target. While mTORC1 activity is required for full expression of some pain modalities, the effects of pathway activation on nociceptor phenotypes and sensory behaviors are currently unknown. To address this, we genetically activated mTORC1 in mouse peripheral sensory neurons by conditional deletion of its negative regulator Tuberous Sclerosis Complex 2 (Tsc2). Consistent with the well-known role of mTORC1 in regulating cell size, soma size and axon diameter of C-nociceptors were increased in Tsc2-deleted mice. Glabrous skin and spinal cord innervation by C-fiber neurons were also disrupted. Transcriptional profiling of nociceptors enriched by fluorescence-associated cell sorting (FACS) revealed downregulation of multiple classes of ion channels as well as reduced expression of markers for peptidergic nociceptors in Tsc2-deleted mice. In addition to these changes in innervation and gene expression, Tsc2-deleted mice exhibited reduced noxious heat sensitivity and decreased injury-induced cold hypersensitivity, but normal baseline sensitivity to cold and mechanical stimuli. Together, these data show that excess mTORC1 activity in sensory neurons produces changes in gene expression, neuron morphology and sensory behavior. PMID:29766046

Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice.

PubMed

Mabe, Abigail M; Hoover, Donald B

2009-04-01

Previous work provided indirect evidence that the neurotrophic factor neurturin (NRTN) is required for normal cholinergic innervation of the heart. This study used nrtn knockout (KO) and wild-type (WT) mice to determine the effect of nrtn deletion on cardiac cholinergic innervation and function in the adult heart. Immunohistochemistry, confocal microscopy, and quantitative image analysis were used to directly evaluate intrinsic cardiac neuronal development. Atrial acetylcholine (ACh) levels were determined as an indirect index of cholinergic innervation. Cholinergic function was evaluated by measuring negative chronotropic responses to right vagal nerve stimulation in anaesthetized mice and responses of isolated atria to muscarinic agonists. KO hearts contained only 35% the normal number of cholinergic neurons, and the residual cholinergic neurons were 15% smaller than in WT. Cholinergic nerve density at the sinoatrial node was reduced by 87% in KOs, but noradrenergic nerve density was unaffected. Atrial ACh levels were substantially lower in KO mice (0.013 +/- 0.004 vs. 0.050 +/- 0.011 pmol/microg protein; P < 0.02) as expected from cholinergic neuron and nerve fibre deficits. Maximum bradycardia evoked by vagal stimulation was reduced in KO mice (38 +/- 6% vs. 69 +/- 3% decrease at 20 Hz; P < 0.001), and chronotropic responses took longer to develop and fade. In contrast to these deficits, isolated atria from KO mice had normal post-junctional sensitivity to carbachol and bethanechol. These findings demonstrate that NRTN is essential for normal cardiac cholinergic innervation and cholinergic control of heart rate. The presence of residual cardiac cholinergic neurons and vagal bradycardia in KO mice suggests that additional neurotrophic factors may influence this system.

Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve.

PubMed

Uludag, Mehmet; Aygun, Nurcihan; Isgor, Adnan

2017-06-01

The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 ± 1583 μV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 ± 630 μV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 ± 280 μV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 ± 229 μV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively.

"Fast" and "slow" skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method.

PubMed

Jami, L; Lan-Couton, D; Malmgren, K; Petit, J

1978-07-01

The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast beta axons and to assess the total proportion of both fast and slow beta-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that beta axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag1 fibers in the others. As this latter location is characteristic of slow dynamic beta axons, it was concluded that both slow and fast beta axons occur regularly in the motor supply to tenuissimus. beta-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow beta axons onto the same spindle.

Spatio-temporal specialization of GABAergic septo-hippocampal neurons for rhythmic network activity.

PubMed

Unal, Gunes; Crump, Michael G; Viney, Tim J; Éltes, Tímea; Katona, Linda; Klausberger, Thomas; Somogyi, Peter

2018-03-03

Medial septal GABAergic neurons of the basal forebrain innervate the hippocampus and related cortical areas, contributing to the coordination of network activity, such as theta oscillations and sharp wave-ripple events, via a preferential innervation of GABAergic interneurons. Individual medial septal neurons display diverse activity patterns, which may be related to their termination in different cortical areas and/or to the different types of innervated interneurons. To test these hypotheses, we extracellularly recorded and juxtacellularly labeled single medial septal neurons in anesthetized rats in vivo during hippocampal theta and ripple oscillations, traced their axons to distant cortical target areas, and analyzed their postsynaptic interneurons. Medial septal GABAergic neurons exhibiting different hippocampal theta phase preferences and/or sharp wave-ripple related activity terminated in restricted hippocampal regions, and selectively targeted a limited number of interneuron types, as established on the basis of molecular markers. We demonstrate the preferential innervation of bistratified cells in CA1 and of basket cells in CA3 by individual axons. One group of septal neurons was suppressed during sharp wave-ripples, maintained their firing rate across theta and non-theta network states and mainly fired along the descending phase of CA1 theta oscillations. In contrast, neurons that were active during sharp wave-ripples increased their firing significantly during "theta" compared to "non-theta" states, with most firing during the ascending phase of theta oscillations. These results demonstrate that specialized septal GABAergic neurons contribute to the coordination of network activity through parallel, target area- and cell type-selective projections to the hippocampus.

The morphology and innervation of facial vibrissae in the tammar wallaby, Macropus eugenii.

PubMed Central

Marotte, L R; Rice, F L; Waite, P M

1992-01-01

The morphology of the vibrissal follicles on the mystacial pad of the tammar wallaby is similar to that seen in other species except that the follicles lack a ringwulst or ring sinus. Instead, the mesenchymal sheath is thickened around the central region of the hair shaft. The follicle is innervated by both deep and superficial vibrissal nerves. The deep nerve enters as 4-11 fascicles which can be in close proximity or widely distributed around the hair. C1 follicles received more myelinated nerve fibres (252 +/- 31) than the smaller C4 follicles (174 +/- 43). The deep vibrissal nerve supplies the thickened mesenchymal sheath, the narrow 'waist' region above and the majority of endings in the inner conical body (ICB), while the superficial nerves provide a sparse innervation to the ICB and rete ridge. Receptors present in the follicle were of 4 types: (1) Merkel cells, especially numerous in the outer root sheath of the 'waist' region and occasionally in the ICB and rete ridge; (2) and (3) lanceolate and lamellated endings parallel to the hair shaft in both the mesenchymal thickening and the 'waist' region where they were particularly dense; (4) free nerve endings in the mesenchymal thickening, 'waist' region and ICB. No corpuscular, bulbous or Ruffini endings were seen. The innervation of the intervibrissal fur was similar to that described in other species. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:1487434

Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium.

PubMed

Kakinuma, Yoshihiko; Akiyama, Tsuyoshi; Sato, Takayuki

2009-09-01

Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer's disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle, we assessed the hypothesis that ACh is produced by cardiomyocytes, which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase (ChAT) in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy, suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However, with atropine, the basal ACh content was reduced. In response to exogenous ACh or pilocarpine, cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression, and, finally, the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA accelerated cellular energy metabolism, which is suppressed by ACh. Although physostigmine had a minimal effect on the ChAT promoter activity by inhibiting acetylcholinesterase, donepezil resulted in elevation of the activity, protein expression and intracellular ACh level even in the presence of sufficient physostigmine. Orally administered donepezil in mice increased the ChAT promoter activity in a reporter gene-transferred quadriceps femoris muscle and the amount of cardiac ChAT protein. These findings suggest that cardiomyocytes possess an ACh synthesis system, which is positively modulated by cholinergic stimuli. Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles.

Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models

PubMed Central

Hartwig, N. R.; Kalmbach, N.; Klietz, M.; Anlauf, M.; Eiden, L. E.; Weihe, E.

2014-01-01

Aims/hypothesis Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have been employed for pancreatic islet imaging in humans. Since reports on TBZ-based VMAT2 imaging in rodent pancreas have been fraught with confusion, we compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimise TBZ imaging in humans. Methods We used a panel of highly sensitive VMAT2 antibodies developed against equivalently antigenic regions of the transporter from each species in combination with immunostaining for insulin and species-specific in situ hybridisation probes. Individual pancreatic islets were obtained by laser-capture microdissection and subjected to analysis of mRNA expression of VMAT2. Results The VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells (but not other pancreatic endocrine cell types) in the pancreas of pigs and humans. VMAT2- and tyrosine hydroxylase co-positive (catecholaminergic) innervation was less abundant in humans than in rodents. VMAT2-positive mast cells were identified in the pancreas of all species. Conclusions/interpretation Primates and pigs are suitable models for TBZ imaging of beta cells. Rodents, because of a complete lack of VMAT2 expression in the endocrine pancreas, are a ‘null’ model for assessing interference with BCM measurements by VMAT2-positive mast cells and sympathetic innervation in the pancreas. PMID:23404442

Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice.

PubMed

Brown, T Christopher; Bond, Cherie E; Hoover, Donald B

2018-03-01

Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantification of Trapezius Muscle Innervation During Neck Dissections: Cervical Plexus Versus the Spinal Accessory Nerve.

PubMed

Svenberg Lind, Clara; Lundberg, Bertil; Hammarstedt Nordenvall, Lalle; Heiwe, Susanne; Persson, Jonas K E; Hydman, Jonas

2015-11-01

Despite increasing use of selective, nerve-sparing surgical techniques during neck dissections, the reported rate of postoperative paralysis of the trapezius muscle is still high. The aim of the study is to measure and compare motor inflow to the trapezius muscle, in order to better understand the peripheral neuroanatomy. Intraoperative nerve monitoring (electroneurography) in patients undergoing routine neck dissection (n=18). The innervation of the 3 functional parts of the trapezius muscle was mapped and quantified through compound muscle action potentials. In 18/18 (100%) of the patients, the spinal accessory nerve (SAN) innervated all parts of the trapezius muscle. In 7/18 (39%) of the patients, an active motor branch from the cervical plexus was detected, equally distributed to all functional parts of the trapezius muscle, at levels comparable to the SAN. Compared to the SAN, branches from cervical plexus provide a significant amount of neural input to all parts of the trapezius muscle. Intraoperative nerve monitoring can be used in routine neck dissections to detect these branches, which may be important following surgical injury to the SAN. © The Author(s) 2015.

The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain.

PubMed

Jimenez-Andrade, Juan M; Mantyh, William G; Bloom, Aaron P; Freeman, Katie T; Ghilardi, Joseph R; Kuskowski, Michael A; Mantyh, Patrick W

2012-05-01

As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4-month-old), middle-aged (13-month-old) and old (36-month-old) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP(+) and NF200(+) nerve fibers that innervate the bone remained remarkably unchanged as did the severity of acute skeletal fracture pain. Thus, while bone mass, quality, and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

PubMed

DiBona, G F

2000-11-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

Functionally specific renal sympathetic nerve fibers: role in cardiovascular regulation.

PubMed

DiBona, G F

2001-06-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs through mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers and an innervation that is shared among all the effectors. This arrangement facilitates maximum flexibility in the coordination of the tubules, the blood vessels, and the juxtaglomerular granular cells so as to produce physiologically appropriate responses to a variety of homeostatic requirements.

Aging is accompanied by a subfield-specific reduction of serotonergic fibers in the tree shrew hippocampal formation.

PubMed

Keuker, Jeanine I H; Keijser, Jan N; Nyakas, Csaba; Luiten, Paul G M; Fuchs, Eberhard

2005-12-01

The hippocampal formation is a crucial structure for learning and memory, and serotonin together with other neurotransmitters is essential in these processes. Although the effects of aging on various neurotransmitter systems in the hippocampus have been extensively investigated, it is not entirely clear whether or how the hippocampal serotonergic innervation changes during aging. Rat studies, which have mostly focused on aging-related changes in the dentate gyrus, have implied a loss of hippocampal serotonergic fibers. We used the tree shrew (Tupaia belangeri), an intermediate between insectivores and primates, as a model of aging. We applied immunocytochemistry with an antibody against serotonin to assess serotonergic fiber densities in the various hippocampal subfields of adult (0.9-1.3 years) and old (5-7 years) tree shrews. Our results have revealed a reduction of serotonergic fiber densities in the stratum radiatum of CA1 and CA3, and in the stratum oriens of CA3. A partial depletion of serotonin in the hippocampal formation, as can be expected from our current observations, will probably have an impact on the functioning of hippocampal principal neurons. Our findings also indicate that the rat and the tree shrew hippocampal serotonergic innervation show some variations that seem to be differentially affected during aging.

Regeneration of axotomized olfactory neurons in young and adult locusts quantified by fasciclin I immunofluorescence.

PubMed

Wasser, Hannah; Biller, Alexandra; Antonopoulos, Georgios; Meyer, Heiko; Bicker, Gerd; Stern, Michael

2017-04-01

The olfactory pathway of the locust Locusta migratoria is characterized by a multiglomerular innervation of the antennal lobe (AL) by olfactory receptor neurons (ORNs). After crushing the antenna and thereby severing ORN axons, changes in the AL were monitored. First, volume changes were measured at different times post-crush with scanning laser optical tomography in 5th instar nymphs. AL volume decreased significantly to a minimum volume at 4 days post-crush, followed by an increase. Second, anterograde labeling was used to visualize details in the AL and antennal nerve (AN) during de- and regeneration. Within 24 h post-crush (hpc) the ORN fragments distal to the lesion degenerated. After 48 hpc, regenerating fibers grew through the crush site. In the AL, labeled ORN projections disappeared completely and reappeared after a few days. A weak topographic match between ORN origin on the antenna and the position of innervated glomeruli that was present in untreated controls did not reappear after regeneration. Third, the cell surface marker fasciclin I that is expressed in ORNs was used for quantifying purposes. Immunofluorescence was measured in the AL during de- and regeneration in adults and 5th instar nymphs: after a rapid but transient, decrease, it reappeared. Both processes happen faster in 5th instar nymphs than in adults.

Coronary veins determine the pattern of sympathetic innervation in the developing heart

PubMed Central

Nam, Joseph; Onitsuka, Izumi; Hatch, John; Uchida, Yutaka; Ray, Saugata; Huang, Siyi; Li, Wenling; Zang, Heesuk; Ruiz-Lozano, Pilar; Mukouyama, Yoh-suke

2013-01-01

Anatomical congruence of peripheral nerves and blood vessels is well recognized in a variety of tissues. Their physical proximity and similar branching patterns suggest that the development of these networks might be a coordinated process. Here we show that large diameter coronary veins serve as an intermediate template for distal sympathetic axon extension in the subepicardial layer of the dorsal ventricular wall of the developing mouse heart. Vascular smooth muscle cells (VSMCs) associate with large diameter veins during angiogenesis. In vivo and in vitro experiments demonstrate that these cells mediate extension of sympathetic axons via nerve growth factor (NGF). This association enables topological targeting of axons to final targets such as large diameter coronary arteries in the deeper myocardial layer. As axons extend along veins, arterial VSMCs begin to secrete NGF, which allows axons to reach target cells. We propose a sequential mechanism in which initial axon extension in the subepicardium is governed by transient NGF expression by VSMCs as they are recruited to coronary veins; subsequently, VSMCs in the myocardium begin to express NGF as they are recruited by remodeling arteries, attracting axons toward their final targets. The proposed mechanism underlies a distinct, stereotypical pattern of autonomic innervation that is adapted to the complex tissue structure and physiology of the heart. PMID:23462468

Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

PubMed

Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Defelipe, Javier

2010-01-01

Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges.

PubMed

De Col, Roberto; Messlinger, Karl; Carr, Richard W

2008-02-15

Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na(+)-K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm) but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons.

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

PubMed Central

Mangner, Tom J.; Leonard, William R.; Kumar, Ajay; Granneman, James G.

2017-01-01

Recent work in rodents has demonstrated that basal activity of the local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown adipose tissue (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT in lean young adults. Methods: Twenty adult lean normal subjects (10 women and 10 men; mean age ± SD, 23.3 ± 3.8 y; body mass index, 23.7 ± 2.5 kg/m2) underwent 11C-meta-hydroxyephedrin (11C-HED) and 15O-water PET imaging at rest and after exposure to mild cold (16°C) temperature. In addition, 18F-FDG images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into 2 groups (high BAT and low BAT) based on the presence of 18F-FDG tracer uptake. Blood flow and 11C-HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT and WAT. Whole-body daily energy expenditure (DEE) during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO2) was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: 18F-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 ± 37 g; low-BAT, 16 ± 4 g). 11C-HED RI under thermoneutral conditions significantly predicted 18F-FDG uptake during cold stress (R2 = 0.68, P < 0.01). In contrast to the significant increase of 11C-HED RI during cold in BAT (2.42 ± 0.85 vs. 3.43 ± 0.93, P = 0.02), cold exposure decreased the 11C-HED RI in WAT (0.44 ± 0.22 vs. 0.41 ± 0.18) as a consequence of decreased perfusion (1.22 ± 0.20 vs. 1.12 ± 0.16 mL/100 g/min). The contribution of WAT to whole-body DEE was approximately 150 kcal/d at rest (149 ± 52 kcal/d), which decreased to approximately 100 kcal/d during cold (102 ± 47 kcal/d). Conclusion: The level of sympathetic innervation, as determined by 11C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of 11C-HED RI and 18F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and 18F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat. PMID:27789721

Estradiol-dependent Modulation of Serotonergic Markers in Auditory Areas of a Seasonally Breeding Songbird

PubMed Central

Matragrano, Lisa L.; Sanford, Sara E.; Salvante, Katrina G.; Beaulieu, Michaël; Sockman, Keith W.; Maney, Donna L.

2011-01-01

Because no organism lives in an unchanging environment, sensory processes must remain plastic so that in any context, they emphasize the most relevant signals. As the behavioral relevance of sociosexual signals changes along with reproductive state, the perception of those signals is altered by reproductive hormones such as estradiol (E2). We showed previously that in white-throated sparrows, immediate early gene responses in the auditory pathway of females are selective for conspecific male song only when plasma E2 is elevated to breeding-typical levels. In this study, we looked for evidence that E2-dependent modulation of auditory responses is mediated by serotonergic systems. In female nonbreeding white-throated sparrows treated with E2, the density of fibers immunoreactive for serotonin transporter innervating the auditory midbrain and rostral auditory forebrain increased compared with controls. E2 treatment also increased the concentration of the serotonin metabolite 5-HIAA in the caudomedial mesopallium of the auditory forebrain. In a second experiment, females exposed to 30 min of conspecific male song had higher levels of 5-HIAA in the caudomedial nidopallium of the auditory forebrain than birds not exposed to song. Overall, we show that in this seasonal breeder, (1) serotonergic fibers innervate auditory areas; (2) the density of those fibers is higher in females with breeding-typical levels of E2 than in nonbreeding, untreated females; and (3) serotonin is released in the auditory forebrain within minutes in response to conspecific vocalizations. Our results are consistent with the hypothesis that E2 acts via serotonin systems to alter auditory processing. PMID:21942431

Pain Experience is Somatotopically Organized and Overlaps with Pain Anticipation in the Human Cerebellum.

PubMed

Michelle Welman, F H S; Smit, Albertine E; Jongen, Joost L M; Tibboel, Dick; van der Geest, Jos N; Holstege, Jan C

2018-02-26

Many fMRI studies have shown activity in the cerebellum after peripheral nociceptive stimulation. We investigated whether the areas in the cerebellum that were activated after nociceptive thumb stimulation were separate from those after nociceptive toe stimulation. In an additional experiment, we investigated the same for the anticipation of a nociceptive stimulation on the thumb or toe. For his purpose, we used fMRI after an electrical stimulation of the thumb and toe in 19 adult healthy volunteers. Following nociceptive stimulation, different areas were activated by stimulation on the thumb (lobule VI ipsilaterally and Crus II mainly contralaterally) and toe (lobules VIII-IX and IV-V bilaterally and lobule VI contralaterally), i.e., were somatotopically organized. Cerebellar areas innervated non-somatotopically by both toe and thumb stimulation were the posterior vermis and Crus I, bilaterally. In the anticipation experiment, similar results were found. However, here, the somatotopically activated areas were relatively small for thumb and negligible for toe stimulation, while the largest area was innervated non-somatotopically and consisted mainly of Crus I and lobule VI bilaterally. These findings indicate that nociceptive stimulation and anticipation of nociceptive stimulation are at least partly processed by the same areas in the cerebellum. This was confirmed by an additional conjunction analysis. Based on our findings, we hypothesize that input that is organized in a somatotopical manner reflects direct input from the spinal cord, while non-somatotopically activated parts of the cerebellum receive their information indirectly through cortical and subcortical connections, possibly involved in processing contextual emotional states, like the expectation of pain.

Physiological and morphological characterization of local interneurons in the Drosophila antennal lobe.

PubMed

Seki, Yoichi; Rybak, Jürgen; Wicher, Dieter; Sachse, Silke; Hansson, Bill S

2010-08-01

The Drosophila antennal lobe (AL) has become an excellent model for studying early olfactory processing mechanisms. Local interneurons (LNs) connect a large number of glomeruli and are ideally positioned to increase computational capabilities of odor information processing in the AL. Although the neural circuit of the Drosophila AL has been intensively studied at both the input and the output level, the internal circuit is not yet well understood. An unambiguous characterization of LNs is essential to remedy this lack of knowledge. We used whole cell patch-clamp recordings and characterized four classes of LNs in detail using electrophysiological and morphological properties at the single neuron level. Each class of LN displayed unique characteristics in intrinsic electrophysiological properties, showing differences in firing patterns, degree of spike adaptation, and amplitude of spike afterhyperpolarization. Notably, one class of LNs had characteristic burst firing properties, whereas the others were tonically active. Morphologically, neurons from three classes innervated almost all glomeruli, while LNs from one class innervated a specific subpopulation of glomeruli. Three-dimensional reconstruction analyses revealed general characteristics of LN morphology and further differences in dendritic density and distribution within specific glomeruli between the different classes of LNs. Additionally, we found that LNs labeled by a specific enhancer trap line (GAL4-Krasavietz), which had previously been reported as cholinergic LNs, were mostly GABAergic. The current study provides a systematic characterization of olfactory LNs in Drosophila and demonstrates that a variety of inhibitory LNs, characterized by class-specific electrophysiological and morphological properties, construct the neural circuit of the AL.

Brain BLAQ: Post-hoc thick-section histochemistry for localizing optogenetic constructs in neurons and their distal terminals

PubMed Central

Kupferschmidt, David A.; Cody, Patrick A.; Lovinger, David M.; Davis, Margaret I.

2015-01-01

Optogenetic constructs have revolutionized modern neuroscience, but the ability to accurately and efficiently assess their expression in the brain and associate it with prior functional measures remains a challenge. High-resolution imaging of thick, fixed brain sections would make such post-hoc assessment and association possible; however, thick sections often display autofluorescence that limits their compatibility with fluorescence microscopy. We describe and evaluate a method we call “Brain BLAQ” (Block Lipids and Aldehyde Quench) to rapidly reduce autofluorescence in thick brain sections, enabling efficient axon-level imaging of neurons and their processes in conventional tissue preparations using standard epifluorescence microscopy. Following viral-mediated transduction of optogenetic constructs and fluorescent proteins in mouse cortical pyramidal and dopaminergic neurons, we used BLAQ to assess innervation patterns in the striatum, a region in which autofluorescence often obscures the imaging of fine neural processes. After BLAQ treatment of 250–350 μm-thick brain sections, axons and puncta of labeled afferents were visible throughout the striatum using a standard epifluorescence stereomicroscope. BLAQ histochemistry confirmed that motor cortex (M1) projections preferentially innervated the matrix component of lateral striatum, whereas medial prefrontal cortex projections terminated largely in dorsal striosomes and distinct nucleus accumbens subregions. Ventral tegmental area dopaminergic projections terminated in a similarly heterogeneous pattern within nucleus accumbens and ventral striatum. Using a minimal number of easily manipulated and visualized sections, and microscopes available in most neuroscience laboratories, BLAQ enables simple, high-resolution assessment of virally transduced optogenetic construct expression, and post-hoc association of this expression with molecular markers, physiology and behavior. PMID:25698938

Tissue engineering the mechanosensory circuit of the stretch reflex arc: sensory neuron innervation of intrafusal muscle fibers.

PubMed

Rumsey, John W; Das, Mainak; Bhalkikar, Abhijeet; Stancescu, Maria; Hickman, James J

2010-11-01

The sensory circuit of the stretch reflex arc, composed of specialized intrafusal muscle fibers and type Ia proprioceptive sensory neurons, converts mechanical information regarding muscle length and stretch to electrical action potentials and relays them to the central nervous system. Utilizing a non-biological substrate, surface patterning photolithography and a serum-free medium formulation a co-culture system was developed that facilitated functional interactions between intrafusal muscle fibers and sensory neurons. The presence of annulospiral wrappings (ASWs) and flower-spray endings (FSEs), both physiologically relevant morphologies in sensory neuron-intrafusal fiber interactions, were demonstrated and quantified using immunocytochemistry. Furthermore, two proposed components of the mammalian mechanosensory transduction system, BNaC1 and PICK1, were both identified at the ASWs and FSEs. To verify functionality of the mechanoreceptor elements the system was integrated with a MEMS cantilever device, and Ca(2+) currents were imaged along the length of an axon innervating an intrafusal fiber when stretched by cantilever deflection. This system provides a platform for examining the role of this mechanosensory complex in the pathology of myotonic and muscular dystrophies, peripheral neuropathy, and spasticity inducing diseases like Parkinson's. These studies will also assist in engineering fine motor control for prosthetic devices by improving our understanding of mechanosensitive feedback. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Proposed catalog of the neuroanatomy and the stratified anatomy for the 361 acupuncture points of 14 channels.

PubMed

Chapple, Will

2013-10-01

In spite of the extensive research on acupuncture mechanisms, no comprehensive and systematic peer-reviewed reference list of the stratified anatomical and the neuroanatomical features of all 361 acupuncture points exists. This study creates a reference list of the neuroanatomy and the stratified anatomy for each of the 361 acupuncture points on the 14 classical channels and for 34 extra points. Each acupuncture point was individually assessed to relate the point's location to anatomical and neuroanatomical features. The design of the catalogue is intended to be useful for any style of acupuncture or Oriental medicine treatment modality. The stratified anatomy was divided into shallow, intermediate and deep insertion. A separate stratified anatomy was presented for different needle angles and directions. The following are identified for each point: additional specifications for point location, the stratified anatomy, motor innervation, cutaneous nerve and sensory innervation, dermatomes, Langer's lines, and somatotopic organization in the primary sensory and motor cortices. Acupuncture points for each muscle, dermatome and myotome are also reported. This reference list can aid clinicians, practitioners and researchers in furthering the understanding and accurate practice of acupuncture. Additional research on the anatomical variability around acupuncture points, the frequency of needle contact with an anatomical structure in a clinical setting, and conformational imaging should be done to verify this catalogue. Copyright © 2013. Published by Elsevier B.V.

Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle

PubMed Central

Chao, Lily C.; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F.

2008-01-01

Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared to oxidative muscle and is responsive to β-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including GLUT4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including GLUT4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by shRNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple innervation-dependent genes in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression. PMID:17550977

Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

NASA Technical Reports Server (NTRS)

Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

1995-01-01

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS).

Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+) Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

PubMed

Iwasaki, Yusaku; Shimomura, Kenju; Kohno, Daisuke; Dezaki, Katsuya; Ayush, Enkh-Amar; Nakabayashi, Hajime; Kubota, Naoto; Kadowaki, Takashi; Kakei, Masafumi; Nakata, Masanori; Yada, Toshihiko

2013-01-01

Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs) of vagal afferents in mice. NGs expressed insulin receptor (IR) and insulin receptor substrate-2 (IRS2) mRNA, and some of NGNs were immunoreactive to IR. In patch-clamp and fura-2 microfluorometric studies, insulin (10(-12)∼10(-6) M) depolarized and increased cytosolic Ca(2+) concentration ([Ca(2+)]i) in single NGNs. The insulin-induced [Ca(2+)]i increases were attenuated by L- and N-type Ca(2+) channel blockers, by phosphatidylinositol 3 kinase (PI3K) inhibitor, and in NGNs from IRS2 knockout mice. Half of the insulin-responsive NGNs contained cocaine- and amphetamine-regulated transcript. Neuronal fibers expressing IRs were distributed in/around pancreatic islets. The NGNs innervating the pancreas, identified by injecting retrograde tracer into the pancreas, responded to insulin with much greater incidence than unlabeled NGNs. Insulin concentrations measured in pancreatic vein was 64-fold higher than that in circulation. Elevation of insulin to 10(-7) M recruited a remarkably greater population of NGNs to [Ca(2+)]i increases. Systemic injection of glibenclamide rapidly released insulin and phosphorylated AKT in NGs. Furthermore, in IRS2 knockout mice, insulin action to suppress [Ca(2+)]i in orexigenic ghrelin-responsive neurons in hypothalamic arcuate nucleus was intact while insulin action on NGN was markedly attenuated, suggesting a possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice These data demonstrate that insulin directly activates NGNs via IR-IRS2-PI3K-AKT-cascade and depolarization-gated Ca(2+) influx. Pancreas-innervating NGNs may effectively sense dynamic changes of insulin released in response to nutritional states. These interactions could serve to convey the changes in pancreatic and systemic insulin to the brain.

Development and use of the incremental twitch subtraction MUNE method in mice.

PubMed

Hegedus, Janka; Jones, Kelvin E; Gordon, Tessa

2009-01-01

We have used a technique to estimate the number of functioning motor units (MUNE) innervating a muscle in mice based on twitch tension. The MUNE technique was verified by modeling twitch tensions from isolated ventral root stimulation. Analysis by twitch tensions allowed us to identify motor unit fiber types. The MUNE technique was used to compare normal mice with transgenic superoxide dismutase-1 mutation (G94A) mice to assess the time course of motor unit loss with respect to fiber type. Motor unit loss was found to occur well in advance of behavioral changes and the degree of reinnervation is dependent upon motor unit fiber types.

Evidence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon.

PubMed

Tosounidis, Theodoros; Hadjileontis, Constantine; Triantafyllou, Christos; Sidiropoulou, Varvara; Kafanas, Antonios; Kontakis, George

2013-03-01

The primary purpose of this study was to investigate the sympathetic innervation of the long head of the biceps brachii tendon LHB via immunohistochemical staining for protein S-100 and neuropeptide Y (NPY) in patients with complex proximal humerus fractures, in individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC), and in cadaveric samples with no previously reported shoulder pathology. We investigated the presence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon (LHB) in patients with complex proximal humerus fractures and individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC). The correlation of morphological features with immunohistochemical evidence of neural element presence was also investigated. Forty-one LHB tendon specimens were examined. Seventeen were harvested from patients who underwent hemiarthroplasty for proximal humerus fractures, 14 were from individuals with biceps tendinosis in the context of a large RC tear, and ten were from cadaveric controls with no previous shoulder pathology. Histologic examination was performed using hematoxylin and eosin. Immunohistochemistry was used to detect the expression of the protein S-100, neuropeptide Y, and α1-adrenergic receptors, as well as to characterize the potential neural differentiation of tendon cells. A strong correlation between the expression of NPY/S-100, α1-adrenergic/S-100, and α1-adrenergic/NPY was found. The LHB tendon has sympathetic innervation and α1-adrenergic receptors in acute and chronic pathological conditions. Our results provide useful guidance on the management of tendinosis and the handling of the LHB in hemiarthroplasties for fractures.

Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation.

PubMed

O'Keeffe, Gerard W; Gutierrez, Humberto; Howard, Laura; Laurie, Christopher W; Osorio, Catarina; Gavaldà, Núria; Wyatt, Sean L; Davies, Alun M

2016-02-15

Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFβ) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF. GDF5 had no effect on neuronal survival and influenced axon growth during a narrow window of postnatal development when sympathetic axons are ramifying extensively in their targets in vivo. SCG neurons expressed all receptors capable of participating in GDF5 signaling at this stage of development. Using compartment cultures, we demonstrated that GDF5 exerted its growth promoting effect by acting directly on axons and by initiating retrograde canonical Smad signalling to the nucleus. GDF5 is synthesized in sympathetic targets, and examination of several anatomically circumscribed tissues in Gdf5 null mice revealed regional deficits in sympathetic innervation. There was a marked, highly significant reduction in the sympathetic innervation density of the iris, a smaller though significant reduction in the trachea, but no reduction in the submandibular salivary gland. There was no reduction in the number of neurons in the SCG. These findings show that GDF5 is a novel target-derived factor that promotes sympathetic axon growth and branching and makes a distinctive regional contribution to the establishment of sympathetic innervation, but unlike NGF, plays no role in regulating sympathetic neuron survival.

Corneal Sulfated Glycosaminoglycans and Their Effects on Trigeminal Nerve Growth Cone Behavior In Vitro: Roles for ECM in Cornea Innervation

PubMed Central

Schwend, Tyler; Deaton, Ryan J.; Zhang, Yuntao; Caterson, Bruce; Conrad, Gary W.

2012-01-01

Purpose. Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM–GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation. Methods. Immunostaining using antineuron-specific-β-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy. Effects of purified GAGs on trigeminal nerve growth cone behavior were tested using in vitro neuronal explant cultures. Results. At E9 to E10, nerves exiting the pericorneal nerve ring grew as tight fascicles, advancing straight toward the corneal stroma. In contrast, upon entering the stroma, nerves bifurcated repeatedly as they extended anteriorly toward the epithelium. KS was localized in the path of trigeminal nerves, whereas DS and CSA/C–rich areas were avoided by growth cones. When E10 trigeminal neurons were cultured on different substrates comprised of purified GAG molecules, their neurite growth cone behavior varied depending on GAG type, concentration, and mode of presentation (immobilized versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited neurite growth to varying degrees. Neurites traversing lower, permissive concentrations of immobilized DS and CSA/C displayed increased fasciculation and decreased branching, whereas KS caused decreased fasciculation and increased branching. Enzymatic digestion of sulfated GAGs canceled their effects on trigeminal neurons. Conclusions. Data herein suggest that GAGs may direct the movement of trigeminal nerve growth cones innervating the cornea. PMID:23132805

Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo.

PubMed

Tucker, D C; Torres, A

1992-02-01

To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.

Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

PubMed

Bacle, Guillaume; Gregoire, Jean-Marc; Patat, Frédéric; Clavert, Philippe; de Pinieux, Gonzague; Laulan, Jacky; Lakhal, Walid; Favard, Luc

2017-02-01

Despite their functional importance, the infraspinatus (ISP) and teres minor (TM) muscles have been little investigated. This study aimed to describe the macroscopic morphology, innervation, and inter-relations of the ISP and TM muscles. Forty fresh cadaver dissections and histologic analysis were performed. Three groups of specimens were distinguished according to the rotator cuff tendon status: (1) intact rotator cuff; (2) supraspinatus tendon tears with intact ISP tendon; and (3) both supraspinatus and ISP tendons torn. Muscle fiber organization and muscle and tendon length were recorded. ISP and TM innervation and fiber structure were studied. ISP muscles were composed of three groups of fiber organized in two planes: two superficial groups, with mean pennation angles of, respectively, 27° ± 4° and 23° ± 3° with respect to the axis of the central tendon of the underlying group. TMs were thick fusiform muscles showing a parallel organization; 26 specimens (67 %) had aponeuroses isolating the TM, with a mean length of 5.2 ± 2.7 cm. Rotator cuff lesions were associated with relatively greater ISP tendon than muscle length. Innervation of the ISP muscle comprised 2-4 main branches from the suprascapular nerve and that of the TM 1 branch from the axillary nerve. ISP muscle body morphology derives from three groups of fibers in two planes. The TM has a parallel organization. Several nerve branches innervate the ISP muscle, whereas only one supplies the TM. The limits between the two muscles bodies consist of an aponeurotic fascia in two-thirds of cases.

SYMPATHETIC INNERVATION, NOREPINEPHRINE CONTENT, AND NOREPINEPHRINE TURNOVER IN ORTHOTOPIC AND SPONTANEOUS MODELS OF BREAST CANCER

PubMed Central

Dawes, Ryan P.; Madden, Kelley S.

2016-01-01

Activation of the sympathetic nervous system (SNS) drives breast cancer progression in preclinical breast cancer models, but it has yet to be established if neoplastic and stromal cells residing in the tumor are directly targeted by locally released norepinephrine (NE). In murine orthotopic and spontaneous mammary tumors, tyrosine hydroxylase (TH)+ sympathetic nerves were limited to the periphery of the tumor. No TH+ staining was detected deeper within these tumors, even in regions with a high density of blood vessels. NE concentration was much lower in tumors compared to the more densely innervated spleen, reflecting the relative paucity of tumor TH+ innervation. Tumor and spleen NE concentration decreased with increased tissue mass. In mice treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to selectively destroy sympathetic nerves, tumor NE concentration was reduced approximately 50%, suggesting that the majority of tumor NE is derived from local sympathetic nerves. To evaluate NE utilization, NE turnover in orthotopic 4T1 mammary tumors was compared to spleen under baseline and stress conditions. In non-stressed mice, NE turnover was equivalent between tumor and spleen. In mice exposed to a stressor, tumor NE turnover was increased compared to spleen NE turnover, and compared to non-stressed tumor NE turnover. Together, these results demonstrate that NE in mammary tumors is derived from local sympathetic nerves that synthesize and metabolize NE. However, differences between spleen and tumor NE turnover with stressor exposure suggest that sympathetic NE release is regulated differently within the tumor microenvironment compared to the spleen. Local mammary tumor sympathetic innervation, despite its limited distribution, is responsive to stressor exposure and therefore can contribute to stress-induced tumor progression. PMID:26718447

Growth Hormone (GH) and Rehabilitation Promoted Distal Innervation in a Child Affected by Caudal Regression Syndrome

PubMed Central

Devesa, Jesús; Alonso, Alba; López, Natalia; García, José; Puell, Carlos I.; Pablos, Tamara; Devesa, Pablo

2017-01-01

Caudal regression syndrome (CRS) is a malformation occurring during the fetal period and mainly characterized by an incomplete development of the spinal cord (SC), which is often accompanied by other developmental anomalies. We studied a 9-month old child with CRS who presented interruption of the SC at the L2–L3 level, sacral agenesis, a lack of innervation of the inferior limbs (flaccid paraplegia), and neurogenic bladder and bowel. Given the known positive effects of growth hormone (GH) on neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce recovery from the aforementioned sequelae. The Gross Motor Function Test (GMFM)-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, during 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed for 5 years, the last GH dose being 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and then every 6 months. Six months after commencing the treatment the GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved all muscles over the knees and controlled his sphincters. Three years later he began to walk with crutches, there was plantar flexion, and the GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal areas below the level of the incomplete spinal cord in CRS. It is likely that GH acted on the ependymal SC NSCs, as the hormone does in the neurogenic niches of the brain, and rehabilitation helped to achieve practically full functionality. PMID:28124993

Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation.

PubMed

Connat, J L; Busseuil, D; Gambert, S; Ody, M; Tébaldini, M; Gamboni, S; Faivre, B; Quiquerez, A L; Millet, M; Michaut, P; Rochette, L

2001-12-01

Structural changes of the male rat aorta were followed from birth to old age in male and female rats. In males, the vessel media width and area progressively increase concomitantly with a decrease of nuclei density during ageing, suggesting an hypertrophy of the smooth muscle cells. These correlations were however not evidenced in females. TUNEL-positive cells were found in media of 4 and 6 months in both sexes, mainly on the luminal side and in the adventitia. When biochemical markers were investigated with immunohistochemistry, media was uniformly stained by the anti-vimentin and anti-alpha-smooth actin at all stages investigated. On the contrary, the surface of media stained with anti-desmin decreased during ageing, especially on the luminal side. As observed with electron microscopy, with ageing the endothelium is replaced by small cells with pseudopodia adhering to the vestigial elastic lamina and infiltrating into the extracellular matrix left after the disappearance of smooth muscle cells. In addition, in the older rats (25-29 months) the elastic laminae are completely disorganised. Hypertrophy of the smooth muscle cells was confirmed by this approach. In parallel to this study, perivascular peptidergic innervation was stained with antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) at different ages during the whole life of rats. These peptides are present in stages younger than 6 months, then gradually disappear. In one year animals and older, the peptidergic innervation has totally disappeared. We discuss the possible role of peptidergic innervation in the control of the vessel wall cellular stability during ageing.

Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus

PubMed Central

Adams, M B; McMillen, I C

2000-01-01

We have investigated adrenal mRNA expression of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) following acute hypoxia in fetal sheep before (< 105 days gestation, n = 20) and after (> 125 days gestation, n = 20) the development of adrenal innervation and following pretreatment with the nicotinic receptor anatgonist hexamethonium (n = 12). Total RNA was extracted from fetal adrenal glands collected at specific time points at 3-20 h after the onset of either hypoxia (∼50% reduction in fetal arterial oxygen saturation (SO2) for 30 min), or normoxia. Before 105 days, there was a decrease in adrenal TH mRNA expression at 20 h after hypoxia and adrenal TH mRNA expression was directly related to the changes in arterial PO2 measured during normoxia and hypoxia. After 125 days, adrenal TH mRNA levels were suppressed for up to 12 h following hypoxia. In both age groups, adrenal PNMT mRNA expression increased at 3-5 h after hypoxia and was inversely related to the changes in fetal arterial PO2 during normoxia or hypoxia. After 125 days, the administration of hexamethonium (25 mg kg−1, I. V.) reduced TH mRNA but not PNMT mRNA expression after normoxia. After hexamethonium pretreatment, there was no significant change in either adrenal TH or PNMT mRNA expression following hypoxia. We conclude that acute hypoxia differentially regulates adrenal TH and PNMT mRNA expression in the fetal sheep both before and after the development of adrenal innervation. After the development of adrenal innervation, however, the effect of acute hypoxia upon adrenal TH and PNMT mRNA expression is dependent upon neurogenic input acting via nicotinic receptors. PMID:11118487

Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation.

PubMed

Khan, S A; Sattar, M Z A; Abdullah, N A; Rathore, H A; Abdulla, M H; Ahmad, A; Johns, E J

2015-07-01

This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Nerve-dependent changes in skeletal muscle myosin heavy chain after experimental denervation and cross-reinnervation and in a demyelinating mouse model of Charcot-Marie-Tooth disease type 1A.

PubMed

Maggs, Alison M; Huxley, Clare; Hughes, Simon M

2008-12-01

Innervation regulates the contractile properties of vertebrate muscle fibers, in part through the effect of electrical activity on expression of distinct myosins. Herein we analyze the role of innervation in regulating the accumulation of the general, maturational, and adult forms of rodent slow myosin heavy chain (MyHC) that are defined by the presence of distinct antigenic epitopes. Denervation increases the number of fibers that express general slow MyHC, but it decreases the adult slow MyHC epitope. Cross-reinnervation of slow muscle by a fast nerve leads to an increase in the number of fibers that express fast MyHC. In both cases, there is an increase in the number of fibers that express slow and fast IIA MyHCs, but without the adult slow MyHC epitope. The data suggest that innervation is required for maturation and maintenance of diversity of both slow and fast fibers. The sequence of slow MyHC epitope transitions is a useful biomarker, and it may play a significant role during nerve-dependent changes in muscle fiber function. We applied this detailed muscle analysis to a transgenic mouse model of human motor and sensory neuropathy IA, also known as Charcot-Marie-Tooth disease type 1A (CMT1A), in which electrical conduction in some motor nerves is poor due to demyelination. The mice display atrophy of some muscle fibers and changes in slow and fast MyHC epitope expression, suggestive of a progressive increase in innervation of muscle fibers by fast motor neurons, even at early stages. The potential role of these early changes in disease pathogenesis is assessed.

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism.

PubMed

De Rosa, A; Pellegrino, T; Pappatà, S; Lieto, M; Bonifati, V; Palma, V; Topa, A; Santoro, L; Bilo, L; Cuocolo, A; De Michele, G

2016-02-01

PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

PubMed

Ramsay, D A; Drachman, D B; Drachman, R J; Stanley, E F

1992-05-29

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.

VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord.

PubMed

Llewellyn-Smith, Ida J; Martin, Carolyn L; Fenwick, Natalie M; Dicarlo, Stephen E; Lujan, Heidi L; Schreihofer, Ann M

2007-08-20

Fast excitatory neurotransmission to sympathetic and parasympathetic preganglionic neurons (SPN and PPN) is glutamatergic. To characterize this innervation in spinal autonomic regions, we localized immunoreactivity for vesicular glutamate transporters (VGLUTs) 1 and 2 in intact cords and after upper thoracic complete transections. Preganglionic neurons were retrogradely labeled by intraperitoneal Fluoro-Gold or with cholera toxin B (CTB) from superior cervical, celiac, or major pelvic ganglia or adrenal medulla. Glutamatergic somata were localized with in situ hybridization for VGLUT mRNA. In intact cords, all autonomic areas contained abundant VGLUT2-immunoreactive axons and synapses. CTB-immunoreactive SPN and PPN received many close appositions from VGLUT2-immunoreactive axons. VGLUT2-immunoreactive synapses occurred on Fluoro-Gold-labeled SPN. Somata with VGLUT2 mRNA occurred throughout the spinal gray matter. VGLUT2 immunoreactivity was not noticeably affected caudal to a transection. In contrast, in intact cords, VGLUT1-immunoreactive axons were sparse in the intermediolateral cell column (IML) and lumbosacral parasympathetic nucleus but moderately dense above the central canal. VGLUT1-immunoreactive close appositions were rare on SPN in the IML and the central autonomic area and on PPN. Transection reduced the density of VGLUT1-immunoreactive axons in sympathetic subnuclei but increased their density in the parasympathetic nucleus. Neuronal cell bodies with VGLUT1 mRNA occurred only in Clarke's column. These data indicate that SPN and PPN are densely innervated by VGLUT2-immunoreactive axons, some of which arise from spinal neurons. In contrast, the VGLUT1-immunoreactive innervation of spinal preganglionic neurons is sparse, and some may arise from supraspinal sources. Increased VGLUT1 immunoreactivity after transection may correlate with increased glutamatergic transmission to PPN. (c) 2007 Wiley-Liss, Inc.

A central mesencephalic reticular formation projection to medial rectus motoneurons supplying singly and multiply innervated extraocular muscle fibers.

PubMed

Bohlen, Martin O; Warren, Susan; May, Paul J

2017-06-01

We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal gaze changes. C-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. Here, we tested whether C-group motoneurons in Macaca fascicularis monkeys receive a direct cMRF input by injecting this portion of the reticular formation with anterograde tracers in combination with injection of retrograde tracer into the medial rectus muscle. The results indicate that the cMRF provides a dense, bilateral projection to the region of the medial rectus C-group motoneurons. Numerous close associations between labeled terminals and each multiply innervated fiber motoneuron were present. Within the oculomotor nucleus, a much sparser ipsilateral projection onto some of the A- and B- group medial rectus motoneurons that supply singly innervated fibers was observed. Ultrastructural analysis demonstrated a direct synaptic linkage between anterogradely labeled reticular terminals and retrogradely labeled medial rectus motoneurons in all three groups. These findings reinforce the notion that the cMRF is a critical hub for oculomotility by proving that it contains premotor neurons supplying horizontal extraocular muscle motoneurons. The differences between the cMRF input patterns for C-group versus A- and B-group motoneurons suggest the C-group motoneurons serve a different oculomotor role than the others. The similar patterns of cMRF input to C-group motoneurons and preganglionic Edinger-Westphal motoneurons suggest that medial rectus C-group motoneurons may play a role in accommodation-related vergence. © 2017 Wiley Periodicals, Inc.

ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes

PubMed Central

Piterina, Anna V.; Cloonan, Aidan J.; Meaney, Claire L.; Davis, Laura M.; Callanan, Anthony; Walsh, Michael T.; McGloughlin, Tim M.

2009-01-01

The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment. PMID:20057951

Axonal interferon responses and alphaherpesvirus neuroinvasion

NASA Astrophysics Data System (ADS)

Song, Ren

Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFNgamma, IFNbeta induces a non-canonical, local antiviral response in axons. The activation of a local IFNbeta response in axons represents a new paradigm for early cytokine control of neuroinvasion. And the two response modes induced by the two distinct types of IFN erect an efficient and appropriate barrier against PNS infection.

Palisade endings and proprioception in extraocular muscles: a comparison with skeletal muscles.

PubMed

Lienbacher, Karoline; Horn, Anja K E

2012-12-01

This article describes current views on motor and sensory control of extraocular muscles (EOMs) based on anatomical data. The special morphology of EOMs, including their motor innervation, is described in comparison to classical skeletal limb and trunk muscles. The presence of proprioceptive organs is reviewed with emphasis on the palisade endings (PEs), which are unique to EOMs, but the function of which is still debated. In consideration of the current new anatomical data about the location of cell bodies of PEs, a hypothesis on the function of PEs in EOMs and the multiply innervated muscle fibres they are attached to is put forward.

[Neurogenic inflammation and chronic rhinosinusitis].

PubMed

Lacroix, J S; Ricchetti Coignard, A

2005-10-19

The nasal mucosa is one of the anatomical region which have the highest density of sensory innervation. The function of this sensory innervation is probably linked to the protection of the lower airways against inhalation of airborne particles and potentially harmful substances. Chronic rhinosinusitis (CRS) is associated with nasal obstruction, rhinorrhea, loss of sense of smell and facial pain or headaches. When allergy or specific hyperreactivity, infection, systemic or genetic deseases have been excluded, the diagnosis of non specific hyperreactivity or neurogenic inflammation is proposed. Sensory neuropeptides released by sensory nerves endings have powerful proinflammatory effects. The best treatment yet available include nasal lavages and the local application of topical corticosteroid spray.

Diabetic corneal neuropathy: clinical perspectives.

PubMed

Bikbova, Guzel; Oshitari, Toshiyuki; Baba, Takayuki; Bikbov, Mukharram; Yamamoto, Shuichi

2018-01-01

Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy.

Innervation of periesophageal region of cat's diaphragm - Implication for studies of control of vomiting

NASA Technical Reports Server (NTRS)

Tan, L. K.; Miller, A. D.

1986-01-01

The extent of the region of the diaphragm around the esophagus that displays greatly reduced activity during the expulsive phase of vomiting was determined from electromyographic studies in cats to be about 0.75-1.0 cm from the esophagus. Horseradish peroxidase injected into this region retrogradely labeled motoneurons throughout most of the rostral-caudal extent of the phrenic nucleus, with the exception of caudal C6 and rostral C7. This widespread intermingling of motoneurons that innervate the region of reduced activity with other phrenic motoneurons creates a difficulty for needed follow-up studies of diaphragmatic control during vomiting.

Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis.

PubMed

Jain, Samay; Goldstein, David S

2012-06-01

Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30-40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a "triple whammy" of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. Parkinson disease (PD) is one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. Severe depletion of dopaminergic neurons of the nigrostriatal system characterizes and likely produces the movement disorder (rest tremor, slowness of movement, rigid muscle tone, and postural instability) in PD. Over the past two decades, compelling evidence has accrued that PD also involves loss of noradrenergic neurons in the heart. This finding supports the view that loss of catecholaminergic neurons, both in the nigrostriatal system and the heart, is fundamental in PD. By the time PD manifests clinically, most of the nigrostriatal dopaminergic neurons are already lost. Identifying laboratory measures-biomarkers-of the disease process is therefore crucial for advances in treatment and prevention. Deposition of the protein, alpha-synuclein, in the form of Lewy bodies in catecholaminergic neurons is a pathologic hallmark of PD. Alpha-synucleinopathy in autonomic neurons may occur early in the pathogenetic process. The timing of cardiac noradrenergic denervation in PD is therefore a key issue. This review updates the field of autonomic cardiovascular abnormalities in PD and related disorders, with emphasis on relationships among striatal dopamine depletion, sympathetic noradrenergic denervation, and alpha-synucleinopathy. Copyright © 2011 Elsevier Inc. All rights reserved.

Soft Ultrathin Electronics Innervated Adaptive Fully Soft Robots.

PubMed

Wang, Chengjun; Sim, Kyoseung; Chen, Jin; Kim, Hojin; Rao, Zhoulyu; Li, Yuhang; Chen, Weiqiu; Song, Jizhou; Verduzco, Rafael; Yu, Cunjiang

2018-03-01

Soft robots outperform the conventional hard robots on significantly enhanced safety, adaptability, and complex motions. The development of fully soft robots, especially fully from smart soft materials to mimic soft animals, is still nascent. In addition, to date, existing soft robots cannot adapt themselves to the surrounding environment, i.e., sensing and adaptive motion or response, like animals. Here, compliant ultrathin sensing and actuating electronics innervated fully soft robots that can sense the environment and perform soft bodied crawling adaptively, mimicking an inchworm, are reported. The soft robots are constructed with actuators of open-mesh shaped ultrathin deformable heaters, sensors of single-crystal Si optoelectronic photodetectors, and thermally responsive artificial muscle of carbon-black-doped liquid-crystal elastomer (LCE-CB) nanocomposite. The results demonstrate that adaptive crawling locomotion can be realized through the conjugation of sensing and actuation, where the sensors sense the environment and actuators respond correspondingly to control the locomotion autonomously through regulating the deformation of LCE-CB bimorphs and the locomotion of the robots. The strategy of innervating soft sensing and actuating electronics with artificial muscles paves the way for the development of smart autonomous soft robots. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peripheral vascular responses to heat stress after hindlimb suspension

NASA Technical Reports Server (NTRS)

Looft-Wilson, Robin C.; Gisolfi, Carl V.

2002-01-01

PURPOSE: The purpose of this study was to determine whether hindlimb suspension (which simulates the effects of microgravity) results in impaired hemodynamic responses to heat stress or alterations in mesenteric small artery sympathetic nerve innervation. METHODS: Over 28 d, 16 male Sprague-Dawley rats were hindlimb-suspended, and 13 control rats were housed in the same type of cage. After the treatment, mean arterial pressure (MAP), colonic temperature (Tcol), and superior mesenteric and iliac artery resistances (using Doppler flowmetry) were measured during heat stress [exposure to 42 degrees C until the endpoint of 80 mm Hg blood pressure was reached (75 +/- 9 min); endpoint Tcore = 43.6 +/- 0.2] while rats were anesthetized (sodium pentobarbital, 50 mg x kg(-1) BW). RESULTS: Hindlimb-suspended and control rats exhibited similar increases in Tcol, MAP, and superior mesenteric artery resistance, and similar decreases in iliac resistance during heat stress (endpoint was a fall in MAP below 80 mm Hg). Tyrosine hydroxylase immunostaining indicated similar sympathetic nerve innervation in small mesenteric arteries from both groups. CONCLUSION: Hindlimb suspension does not alter the hemodynamic or thermoregulatory responses to heat stress in the anesthetized rat or mesenteric sympathetic nerve innervation, suggesting that this sympathetic pathway is intact.

Limited distal organelles and synaptic function in extensive monoaminergic innervation.

PubMed

Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

2017-08-01

Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

Gustatory otalgia and wet ear syndrome: a possible cross-innervation after ear surgery.

PubMed

Saito, H

1999-04-01

The chorda tympani and Arnold's nerves have close approximation to each other and their cross-innervation is possible after ear surgery. A retrospective study was performed with a temporal bone pathology case and two clinical cases as representatives of such a possibility. Patients had severe otalgia and wet ear during gustatory stimulation. A temporal bone pathology case was studied under a light microscope. Earache and/or wet ear were provoked during gustatory stimulation. Wet ear was tested with iodine-starch reaction after the subject tasted lemon juice. The temporal bone specimen has clusters of regenerated fibers in the tympanic cavity in the area of the chorda tympani and Arnold's nerves, suggesting a possibility of mixing. There are regenerated fibers in the iter chordae anterius, showing successful bridging of the chorda tympani nerves across a long gap. Detachment of the skin over the operated mastoid bowl obscured signs in one clinical case. Another clinical case of gustatory wet ear showed objective evidence of cross-innervation with iodine-starch reaction. The detachment procedure and iodine-starch reaction were the proofs that the signs were related to regenerated fibers. This is the first report of gustatory otalgia and wet ear after ear surgery.

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees

PubMed Central

Barger, Nicole; Taglialatela, Jared P.; Gendron-Fitzpatrick, Annette; Hof, Patrick R.; Hopkins, William D.; Sherwood, Chet C.

2016-01-01

Humans’ closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. PMID:26475872

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells

PubMed Central

Amoroso, Mackenzie W.; Croft, Gist F.; Williams, Damian J.; O’Keeffe, Sean; Carrasco, Monica A.; Davis, Anne R.; Roybon, Laurent; Oakley, Derek H.; Maniatis, Tom; Henderson, Christopher E.; Wichterle, Hynek

2013-01-01

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3−). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. PMID:23303937

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys.

PubMed

Ayajiki, Kazuhide; Kobuchi, Shuhei; Tawa, Masashi; Okamura, Tomio

2012-01-01

The functional roles of the nitrergic nerves innervating the monkey cerebral artery were evaluated in a tension-response study examining isolated arteries in vitro and cerebral angiography in vivo. Nicotine produced relaxation of arteries by stimulation of nerve terminals innervating isolated monkey arteries irrigating the cerebrum, cerebellum and brain stem. Relaxation of arteries induced by nicotine was abolished by treatment with N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor, and was restored by addition of L-arginine. Cerebral angiography showed that electrical stimulation of the unilateral greater petrosal nerve, which connects to the pterygopalatine ganglion via the parasympathetic ganglion synapse, produced vasodilatation of the anterior, middle and posterior cerebral arteries in the stimulated side. However, stimulation failed to produce vasodilatation of the superior and anterior-inferior cerebellar arteries and the basilar artery in anesthetized monkeys. Therefore, nitrergic nerves derived from the pterygopalatine ganglion appear to regulate cerebral vasomotor function. In contrast, circulation in the cerebellum and brain stem might be regulated by nitrergic nerves originating not from the pterygopalatine ganglion, but rather from an unknown ganglion (or ganglia).

Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation.

PubMed

Tellman, Matthew W; Bahler, Clinton D; Shumate, Ashley M; Bacallao, Robert L; Sundaram, Chandru P

2015-05-01

Chronic pain is a prominent feature of autosomal dominant polycystic kidney disease that is difficult to treat and manage, often resulting in a decrease in quality of life. Understanding the underlying anatomy of renal innervation and the various etiologies of pain that occur in autosomal dominant polycystic kidney disease can help guide proper treatments to manage pain. Reviewing previously studied treatments for pain in autosomal dominant polycystic kidney disease can help characterize treatment in a stepwise fashion. We performed a literature search of the etiology and management of pain in autosomal dominant polycystic kidney disease and the anatomy of renal innervation using PubMed® and Embase® from January 1985 to April 2014 with limitations to human studies and English language. Pain occurs in the majority of patients with autosomal dominant polycystic kidney disease due to renal, hepatic and mechanical origins. Patients may experience different types of pain which can make it difficult to clinically confirm its etiology. An anatomical and histological evaluation of the complex renal innervation helps in understanding the mechanisms that can lead to renal pain. Understanding the complex nature of renal innervation is essential for surgeons to perform renal denervation. The management of pain in autosomal dominant polycystic kidney disease should be approached in a stepwise fashion. Acute causes of renal pain must first be ruled out due to the high incidence in autosomal dominant polycystic kidney disease. For chronic pain, nonopioid analgesics and conservative interventions can be used first, before opioid analgesics are considered. If pain continues there are surgical interventions such as renal cyst decortication, renal denervation and nephrectomy that can target pain produced by renal or hepatic cysts. Chronic pain in patients with autosomal dominant polycystic kidney disease is often refractory to conservative, medical and other noninvasive treatments. There are effective surgical procedures that can be performed when more conservative treatments fail. Laparoscopic cyst decortication has been well studied and results in the relief of chronic renal pain in the majority of patients. In addition, renal denervation has been used successfully and could be performed concurrently with cyst decortication. Nephrectomy should be reserved for patients with intractable pain and renal failure when other modalities have failed. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide.

PubMed

Redd, P E; Byers, M R

1994-05-01

Junctional epithelium (JE) is a rapidly proliferating tissue that connects the gum to the tooth, that provides a free surface for bidirectional movement of substances between the body and the oral cavity, and that participates in defense against bacterial infection. It is innervated by numerous sensory nerve fibers that are immunoreactive (IR) for neuropeptides such as calcitonin gene-related peptide (CGRP), and for low affinity nerve growth factor receptor (p75-NGFR). Basal epithelial cells of the JE and of adjacent sulcular epithelium also have intense p75-NGFR-IR. In the present study we removed a wedge of the free gingiva and JE from the anterior side of the maxillary first molar of adult rats, and then studied the return of nerve fibers during tissue regeneration from 1-63 days after gingivectomy. The nerve fibers entered the adjacent healing sulcular epithelium before innervating the new JE, in both cases prior to return of epithelial cell p75-NGFR-IR. The regenerating nerve fibers completely bypassed the zone of epithelial down-growth (long junctional epithelium, LJE) that was briefly present along the tooth from 1-3 weeks after injury. The LJE did not have p75-NGFR-IR and was gradually replaced by a modified thicker regenerated junctional epithelium (RJE). The RJE was attached along the injured root surface, had numerous nerves in basal layers, and it had begun to regain p75-NGFR-IR staining of basal epithelial cells by 22 d. Regenerating nerve fibers at 6-10 d had unusually weak CGRP-IR and greatly increased p75-NGFR-IR. Both nerve stains had returned to normal by 3-6 weeks. The intense p75-NGFR-IR of regenerating nerves was found on both axonal and Schwann cell membranes using electron microscopic immunocytochemistry. In both the normal and regenerating JE, nerve fibers were rare in the attachment layers next to the anterior side of the maxillary first molar, compared to well-innervated basal layers. The complete avoidance of LJE by regenerating nerve fibers and its lack of p75-NGFR-IR suggest that its functions do not require innervation and that it does not make neurotrophic growth factors.

Functional deficits in carpal tunnel syndrome reflect reorganization of primary somatosensory cortex

PubMed Central

Kettner, Norman; Holden, Jameson; Lee, Jeungchan; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Im, Jaehyun; Libby, Alexandra; Mezzacappa, Pia; Morse, Leslie R.; Park, Kyungmo; Audette, Joseph; Tommerdahl, Mark; Napadow, Vitaly

2014-01-01

Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20–60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit’s contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = −0.31, P < 0.05), and number of pinch/release cycles (r = −0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients. PMID:24740988

3-D Reconstruction of Macular Type II Cell Innervation Patterns in Space-Flight and Control Rats

NASA Technical Reports Server (NTRS)

Ross, Muriel Dorothy; Montgomery, K.; Linton, S.; Cheng, R.; Tomko, David L. (Technical Monitor)

1995-01-01

A semiautomated method for reconstructing objects from serial thin sections has been developed in the Biocomputation Center. The method is being used to completely, for the first time, type II hair cells and their innervations. The purposes are to learn more about the fundamental circuitry of the macula on Earth and to determine whether changes in connectivities occur under space flight conditions. Data captured directly from a transmission electron microscope via a video camera are sent to a graphics workstation. There, the digitized micrographs are mosaicked into sections and contours are traced, registered and displayed by semiautomated methods. Current reconstructions are of type II cells from the medial part of rat maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that typical type II cells receive processes from tip to six nearby calyces or afferents. Nearly all processes are elongated and have bouton-like enlargements; some have numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approximately 1/3 of the processes innervale 2 or 3 type II cells or a neighboring cluster. From 2% to 6% of the cells resemble type I cells morphologically but have demi-calyces. Thus far, increments in synaptic number in type II cells of flight rats are prominent along processes that supply two hair cells. It is clear that reconstruction methods provide insights into details of macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields through feed back-feed forward connections, and for dynamic alterations in receptive field range and activity during preprocessing of linear acceleratory information by the maculas. The reconstruction method we have developed will find further applications in the study of the details of neuronal architecture of more complex systems, to seek out shared organizational properties or neuronal networks and to understand better localization of synaptic changes in altered environments.

The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.

PubMed

Valdez, Chris M; Murphy, Geoffrey G; Beg, Asim A

2016-09-01

Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoskeleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, α2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of α2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of α2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that α2-chimaerin serves as a "brake" to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity. Copyright © 2016 Elsevier Inc. All rights reserved.

The first data on the innervation of the lophophore in the rhynchonelliform brachiopod Hemithiris psittacea: what is the ground pattern of the lophophore in lophophorates?

PubMed

Temereva, Elena N; Kuzmina, Tatyana V

2017-07-31

The nervous system in brachiopods has seldom been studied with modern methods. An understanding of lophophore innervation in adult brachiopods is useful for comparing the innervation of the same lophophore type among different brachiopods and can also help answer questions about the monophyly of the lophophorates. Although some brachiopods are studied with modern methods, rhynchonelliform brachiopods still require investigation. The current study used transmission electron microscopy, immunocytochemistry, and confocal laser scanning microscopy to investigate the nerve system of the lophophore and tentacles in the rhynchonelliform Hemithiris psittacea. Four longitudinal nerves pass along each brachium of the lophophore: the main, accessory, second accessory, and lower. The main brachial nerve extends at the base of the dorsal side of the brachial fold and gives rise to the cross nerves, passing through the extracellular matrix to the tentacles. Cross nerves skirt the accessory brachial nerve, branch, and penetrate into adjacent outer and inner tentacles, where they are referred to as the frontal tentacular nerves. The second accessory nerve passes along the base of the inner tentacles. This nerve consists of Ʊ-like parts, which repetitively skirt the frontal and lateral sides of the inner tentacle and the frontal sides of the outer tentacles. The second accessory nerve gives rise to the latero-frontal nerves of the inner and outer tentacles. The abfrontal nerves of the inner tentacles also originate from the second accessory nerve, whereas the abfrontal nerves of the outer tentacles originate from the lower brachial nerve. The lower brachial nerve extends along the outer side of the lophophore brachia and gives rise to the intertentacular nerves, which form a T-like branch and penetrate the adjacent outer tentacles where they are referred to as abfrontal nerves. The paired outer radial nerves start from the lower brachial nerve, extend into the second accessory nerve, and give rise to the lateroabfrontal tentacular nerves of the outer tentacles. The innervation of the lophophore in the rhynchonelliform Hemithiris psittacea differs from that in the inarticulate Lingula anatina in several ways. The accessory brachial nerve does not participate in the innervation of the tentacles in H. psittacea as it does in L. anatina. The second accessory nerve is present in H. psittacea but not in L. anatina. There are six tentacular nerves in the outer tentacles of H. psittacea but only four in all other brachiopods studied to date. The reduced contribution of the accessory brachial nerve to tentacle innervation may reflect the general pattern of reduction of the inner lophophoral nerve in both phoronids and brachiopods. Bryozoan lophophores, in contrast, have a weakened outer nerve and a strengthened inner nerve. Our results suggest that the ancestral lophophore of all lophophorates had a simple shape but many nerve elements.

Direct mass spectrometric peptide profiling and sequencing of nervous tissues to identify peptides involved in male copulatory behavior in Lymnaea stagnalis

NASA Astrophysics Data System (ADS)

Dreisewerd, Klaus; Kingston, Robert; Geraerts, Wijnand P. M.; Li, Ka Wan

1997-12-01

Matrix-assisted laser desorption mass spectrometry (MALDI-MS) was performed directly on a small piece of single penis nerve of the pond snail, Lymnaea stagnalis, and reveals the presence of complex peptide profiles, including many hitherto undescribed peptides. Two of the peptides have molecular weights corresponding exactly to the previously described Lymnaea small cardioactive peptides (SCP) A and B. We confirmed their identities by structural characterization of the two peptides directly from a single penis nerve by matrix-assisted laser desorption ionization high-energy collision tandem MS analysis. MALDI-MS of nervous tissues also demonstrates that a cluster of central neurons, which send their axons to the penis nerve, contain the two peptides. As the penis nerve is the nerve that innervates the penis complex, we propose that the peptides are involved in the modulation of male copulatory processes. A bioassay indeed showed that the peptides increase the contraction frequency of the vas deference in a dose-dependent manner. The results demonstrate the potential of direct MALDI-MS analysis of nervous tissue to complement or substitute conventional biochemical techniques for the identification and localization of neuropeptides.

Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease.

PubMed

Braun, David J; Kalinin, Sergey; Feinstein, Douglas L

2017-01-01

Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes to the evolution of neuroinflammation and neurodegeneration in a variety of conditions and diseases. One cause of LC damage may be loss of neurotrophic support from LC target regions. We tested this hypothesis by conditional unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To evaluate the consequences of BDNF loss in the context of neurodegeneration, the mice harbored familial mutations for human amyloid precursor protein and presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion also reduced noradrenergic innervation in the hippocampus, the frontal cortex, and molecular layer of the cerebellum, assessed by staining for dopamine beta hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers and size but was without effect on plaque numbers in the striatum, a site with minimal innervation from the LC. Interestingly, cortical Iba1 staining for microglia was reduced by BDNF depletion and was correlated with reduced dopamine beta hydroxylase staining. These data demonstrate that reduction of BDNF levels in an LC target region can cause retrograde damage to LC neurons, leading to exacerbation of neuropathology in distinct LC target areas. Methods to reduce BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative processes normally limited by LC noradrenergic activities.

Functional anorectal disorders.

PubMed

Bharucha, Adil E; Wald, Arnold; Enck, Paul; Rao, Satish

2006-04-01

This report defines criteria for diagnosing functional anorectal disorders (ie, fecal incontinence, anorectal pain, and disorders of defecation). Functional fecal incontinence is defined as the uncontrolled passage of fecal material recurring for > or =3 months in an individual with a developmental age of > or =4 years that is associated with: (1) abnormal functioning of normally innervated and structurally intact muscles, and/or (2) no or minor abnormalities of sphincter structure and/or innervation insufficient to explain fecal incontinence, and/or (3) normal or disordered bowel habits (ie, fecal retention or diarrhea), and/or (4) psychological causes. However, conditions wherein structural and/or neurogenic abnormalities explain the symptom, or are part of a generalized process (eg, diabetic neuropathy) are not included within functional fecal incontinence. Functional fecal incontinence is a common, but underrecognized symptom, which is equally prevalent in men and women, and can often cause considerable distress. The clinical features are useful for guiding diagnostic testing and therapy. Functional anorectal pain syndromes include proctalgia fugax (fleeting pain) and chronic proctalgia; chronic proctalgia may be subdivided into levator ani syndrome and unspecified anorectal pain, which are defined by arbitrary clinical criteria. Functional defecation disorders are characterized by 2 or more symptoms of constipation, with > or =2 of the following features during defecation: impaired evacuation, inappropriate contraction of the pelvic floor muscles, and inadequate propulsive forces. Functional disorders of defecation may be amenable to pelvic floor retraining by biofeedback therapy (such as dyssynergic defecation).

Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges

PubMed Central

De Col, Roberto; Messlinger, Karl; Carr, Richard W

2008-01-01

Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na+–K+-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na+–K+-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10–300 μm) and carbamazepine (30–500 μm) but not tetrodotoxin (TTX, 10–80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na+–K+-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons. PMID:18096592

Rapid Effects of Hearing Song on Catecholaminergic Activity in the Songbird Auditory Pathway

PubMed Central

Matragrano, Lisa L.; Beaulieu, Michaël; Phillip, Jessica O.; Rae, Ali I.; Sanford, Sara E.; Sockman, Keith W.; Maney, Donna L.

2012-01-01

Catecholaminergic (CA) neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH), a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses. PMID:22724011

Biotechnological Management of Skin Burn Injuries: Challenges and Perspectives in Wound Healing and Sensory Recovery.

PubMed

Girard, Dorothée; Laverdet, Betty; Buhé, Virginie; Trouillas, Marina; Ghazi, Kamélia; Alexaline, Maïa M; Egles, Christophe; Misery, Laurent; Coulomb, Bernard; Lataillade, Jean-Jacques; Berthod, François; Desmoulière, Alexis

2017-02-01

Many wound management protocols have been developed to improve wound healing after burn with the primordial aim to restore the barrier function of the skin and also provide a better esthetic outcome. Autologous skin grafts remain the gold standard in the treatment of skin burn, but this treatment has its limitation especially for patients presenting limited donor sites due to extensive burn areas. Deep burn injuries also alter the integrity of skin-sensitive innervation and have an impact on patient's quality of life by compromising perceptions of touch, temperature, and pain. Thus, patients can suffer from long-term disabilities ranging from cutaneous sensibility loss to chronic pain. The cellular mechanisms involved in skin reinnervation following injury are not elucidated yet. Depending on the depth of the burn, nerve sprouting can occur from the wound bed or the surrounding healthy tissue, but somehow this process fails to provide correct reinnervation of the wound during scarring. In addition, several clinical observations indicate that damage to the peripheral nervous system influences wound healing, resulting in delayed wound healing or chronic wounds, underlining the role of innervation and neuromediators for normal cutaneous tissue repair development. Promising tissue engineering strategies, including the use of biomaterials, skin substitutes, and stem cells, could provide novel alternative treatments in wound healing and help in improving patient's sensory recovery.

Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles.

PubMed

Kwon, Y W; Abbondanzo, S J; Stewart, C L; Gurney, M E

1995-09-01

We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.

Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans.

PubMed

Trotter, Paula Diane; McGlone, Francis; McKie, Shane; McFarquhar, Martyn; Elliott, Rebecca; Walker, Susannah Claire; Deakin, John Francis William

2016-08-01

C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT-activating touch engages the pro-social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT-innervated forearm skin and CT non-innervated finger skin was stroked with three brushes of differing texture, at CT-optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT-activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT-activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Hippocampal Ghrelin-positive neurons directly project to arcuate hypothalamic and medial amygdaloid nuclei. Could they modulate food-intake?

PubMed

Russo, Cristina; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania

2017-07-13

Feeding is a process controlled by a complex of associations between external and internal stimuli. The processes that involve learning and memory seem to exert a strong control over appetite and food intake, which is modulated by a gastrointestinal hormone, Ghrelin (Ghre). Recent studies claim that Ghre is involved in cognitive and neurobiological mechanisms that underlie the conditioning of eating behaviors. The expression of Ghre increases in anticipation of food intake based on learned behaviors. The hippocampal Ghre-containing neurons neurologically influence the orexigenic hypothalamus and consequently the learned feeding behavior. The CA1 field of Ammon's horn of the hippocampus (H-CA1) constitutes the most important neural substrate to control both appetitive and ingestive behavior. It also innervates amygdala regions that in turn innervate the hypothalamus. A recent study also implies that Ghre effects on cue-potentiated feeding behavior occur, at the least, via indirect action on the amygdala. In the present study, we investigate the neural substrates through which endogenous Ghre communicates conditioned appetite and feeding behavior within the CNS. We show the existence of a neural Ghre dependent pathway whereby peripherally-derived Ghre activates H-CA1 neurons, which in turn activate Ghre-expressing hypothalamic and amygdaloid neurons to stimulate appetite and feeding behavior. To highlight this pathway, we use two fluorescent retrograde tracers (Fluoro Gold and Dil) and immunohistochemical detection of Ghre expression in the hippocampus. Triple fluorescent-labeling has determined the presence of H-CA1 Ghre-containing collateralized neurons that project to the hypothalamus and amygdala monosynaptically. We hypothesize that H-Ghre-containing neurons in H-CA1 modulate food-intake behavior through direct pathways to the arcuate hypothalamic nucleus and medial amygdaloid nucleus. Copyright © 2017 Elsevier B.V. All rights reserved.

Extending the socio-sexual brain: arginine-vasopressin immunoreactive circuits in the telencephalon of mice.

PubMed

Otero-Garcia, Marcos; Martin-Sanchez, Ana; Fortes-Marco, Lluis; Martínez-Ricós, Joana; Agustin-Pavón, Carmen; Lanuza, Enrique; Martínez-García, Fernando

2014-05-01

Quantitative analysis of the immunoreactivity for arginine-vasopressin (AVP-ir) in the telencephalon of male (intact and castrated) and female CD1 mice allows us to precisely locate two sexually dimorphic (more abundant in intact than castrated males and females) AVP-ir cell groups in the posterior bed nucleus of the stria terminalis (BST) and the amygdala. Chemoarchitecture (NADPH diaphorase) reveals that the intraamygdaloid AVP-ir cells are located in the intra-amygdaloid BST (BSTIA) rather than the medial amygdala (Me), as previously thought. Then, we have used for the first time tract tracing (combined with AVP immunofluorescence) and fiber-sparing lesions of the BST to analyze the projections of the telencephalic AVP-ir cell groups. The results demonstrate that the posterior BST originates the sexually dimorphic innervation of the lateral septum, the posterodorsal Me and a substance P-negative area in the medioventral striato-pallidum (mvStP).The BSTIA may also contribute to some of these terminal fields. Our material also reveals non-dimorphic AVP-ir processes in two locations of the amygdala. First, the ventral Me shows dendrite-like AVP-ir processes apparently belonging supraoptic neurons, whose possible functions are discussed. Second, the Ce shows sparse, thick AVP-ir axons with high individual variability in density and distribution, whose possible influence on stress coping in relation to the affiliative or agonistic behaviors mediated by the Me are discussed. Finally, we propose that the region of the mvStP showing sexually dimorphic AVP-ir innervation is part of the brain network for socio-sexual behavior, in which it would mediate motivational aspects of chemosensory-guided social interactions.

F-spondin Is Essential for Maintaining Circadian Rhythms

PubMed Central

Carrillo, Gabriela L.; Su, Jianmin; Monavarfeshani, Aboozar; Fox, Michael A.

2018-01-01

The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian behaviors. SCN neurons have intrinsic, self-sustained rhythmicity that is governed by transcription-translation feedback loops. Intrinsic rhythms within the SCN do not match the day-night cycle and are therefore entrained by light-derived cues. Such cues are transmitted to the SCN by a class of intrinsically photosensitive retinal ganglion cells (ipRGCs). In the present study, we sought to identify how axons from ipRGCs target the SCN. While none of the potential targeting cues identified appeared necessary for retinohypothalamic innervation, we unexpectedly identified a novel role for the extracellular matrix protein F-spondin in circadian behavior. In the absence of F-spondin, mice lost their ability to maintain typical intrinsic rhythmicity. Moreover, F-spondin loss results in the displacement of vasoactive intestinal peptide (VIP)-expressing neurons, a class of neurons that are essential for maintaining rhythmicity among SCN neurons. Thus, this study highlights a novel role for F-spondin in maintaining circadian rhythms. PMID:29472844

Spontaneous laryngeal reinnervation following chronic recurrent laryngeal nerve injury.

PubMed

Kupfer, Robbi A; Old, Matthew O; Oh, Sang Su; Feldman, Eva L; Hogikyan, Norman D

2013-09-01

To enhance understanding of spontaneous laryngeal muscle reinnervation following severe recurrent laryngeal nerve injury by testing the hypotheses that 1) nerve fibers responsible for thyroarytenoid muscle reinnervation can originate from multiple sources and 2) superior laryngeal nerve is a source of reinnervation. Prospective, controlled, animal model. A combination of retrograde neuronal labeling techniques, immunohistochemistry, electromyography, and sequential observations of vocal fold mobility were employed in rat model of chronic recurrent laryngeal nerve injury. The current study details an initial set of experiments in sham surgical and denervated group animals and a subsequent set of experiments in a denervated group. At 3 months after recurrent laryngeal nerve resection, retrograde brainstem neuronal labeling identified cells in the characteristic superior laryngeal nerve cell body location as well as cells in a novel caudal location. Regrowth of neuron fibers across the site of previous recurrent laryngeal nerve resection was seen in 87% of examined animals in the denervated group. Electromyographic data support innervation by both the superior and recurrent laryngeal nerves following chronic recurrent laryngeal nerve injury. Following chronic recurrent laryngeal nerve injury in the rat, laryngeal innervation is demonstrated through the superior laryngeal nerve from cells both within and outside of the normal cluster of cells that supply the superior laryngeal nerve. The recurrent laryngeal nerve regenerates across a surgically created gap, but functional significance of regenerated nerve fibers is unclear. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Prolonged passive static stretching-induced innervation zone shift in biceps brachii.

PubMed

Ye, Xin; Beck, Travis W; Wages, Nathan P

2015-05-01

The purpose of this study was to examine the influence of a bout of repeated and prolonged passive static stretching on the innervation zone (IZ) location of the human biceps brachii muscle. Eleven men performed 12 sets of 100-s passive stretches on their biceps brachii. Before (Pre) and immediately after (Post) the stretching intervention, isometric strength was tested during the maximal voluntary contractions (MVCs) of the forearm flexors. The subjects also performed several separate isometric forearm flexion muscle actions at 30%, 50%, and 70% of their predetermined MVCs for examining the locations of the IZ at different contraction intensities. The IZ was identified through multi-channel surface electromyographic (EMG) recordings from a linear electrode array. The stretching intervention induced an average of 10% isometric strength loss for the forearm flexors (mean±SD: Pre-MVC vs. Post-MVC=332.12±59.40 N vs. 299.53±70.51 N; p<0.001). In addition, the average IZ shift was nearly 4.5 mm in average in the proximal direction. However, this shift was not specific to the contraction intensity. We believe that the IZ shift was caused by the elongation of the entire muscle-tendon unit in the proximal direction. Therefore, caution should be taken when using surface EMG technique to examine possible changes in the EMG variables after a stretching protocol, as these variables can be contaminated by the shift of the IZ.

Cholinergic innervation of the zebrafish olfactory bulb.

PubMed

Edwards, Jeffrey G; Greig, Ann; Sakata, Yoko; Elkin, Dimitry; Michel, William C

2007-10-20

A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit-specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine-stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh-stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine-stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB.

Pedal peptide/orcokinin‐type neuropeptide signaling in a deuterostome: The anatomy and pharmacology of starfish myorelaxant peptide in Asterias rubens

PubMed Central

Lin, Ming; Egertová, Michaela; Zampronio, Cleidiane G.; Jones, Alexandra M.

2017-01-01

Abstract Pedal peptide (PP) and orcokinin (OK) are related neuropeptides that were discovered in protostomian invertebrates (mollusks, arthropods). However, analysis of genome/transcriptome sequence data has revealed that PP/OK‐type neuropeptides also occur in a deuterostomian phylum—the echinoderms. Furthermore, a PP/OK‐type neuropeptide (starfish myorelaxant peptide, SMP) was recently identified as a muscle relaxant in the starfish Patiria pectinifera. Here mass spectrometry was used to identify five neuropeptides (ArPPLN1a‐e) derived from the SMP precursor (PP‐like neuropeptide precursor 1; ArPPLNP1) in the starfish Asterias rubens. Analysis of the expression of ArPPLNP1 and neuropeptides derived from this precursor in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed a widespread pattern of expression, with labeled cells and/or processes present in the radial nerve cords, circumoral nerve ring, digestive system (e.g., cardiac stomach) and body wall‐associated muscles (e.g., apical muscle) and appendages (e.g., tube feet and papulae). Furthermore, our data provide the first evidence that neuropeptides are present in the lateral motor nerves and in nerve processes innervating interossicular muscles. In vitro pharmacological tests with SMP (ArPPLN1b) revealed that it causes dose‐dependent relaxation of apical muscle, tube foot and cardiac stomach preparations from A. rubens. Collectively, these anatomical and pharmacological data indicate that neuropeptides derived from ArPPLNP1 act as inhibitory neuromuscular transmitters in starfish, which contrasts with the myoexcitatory actions of PP/OK‐type neuropeptides in protostomian invertebrates. Thus, the divergence of deuterostomes and protostomes may have been accompanied by an inhibitory–excitatory transition in the roles of PP/OK‐type neuropeptides as regulators of muscle activity. PMID:28880392

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults.

PubMed

Muzik, Otto; Mangner, Tom J; Leonard, William R; Kumar, Ajay; Granneman, James G

2017-05-01

Recent work in rodents has demonstrated that basal activity of the local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown adipose tissue (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT in lean young adults. Methods: Twenty adult lean normal subjects (10 women and 10 men; mean age ± SD, 23.3 ± 3.8 y; body mass index, 23.7 ± 2.5 kg/m 2 ) underwent 11 C-meta-hydroxyephedrin ( 11 C-HED) and 15 O-water PET imaging at rest and after exposure to mild cold (16°C) temperature. In addition, 18 F-FDG images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into 2 groups (high BAT and low BAT) based on the presence of 18 F-FDG tracer uptake. Blood flow and 11 C-HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT and WAT. Whole-body daily energy expenditure (DEE) during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO 2 ) was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: 18 F-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 ± 37 g; low-BAT, 16 ± 4 g). 11 C-HED RI under thermoneutral conditions significantly predicted 18 F-FDG uptake during cold stress ( R 2 = 0.68, P < 0.01). In contrast to the significant increase of 11 C-HED RI during cold in BAT (2.42 ± 0.85 vs. 3.43 ± 0.93, P = 0.02), cold exposure decreased the 11 C-HED RI in WAT (0.44 ± 0.22 vs. 0.41 ± 0.18) as a consequence of decreased perfusion (1.22 ± 0.20 vs. 1.12 ± 0.16 mL/100 g/min). The contribution of WAT to whole-body DEE was approximately 150 kcal/d at rest (149 ± 52 kcal/d), which decreased to approximately 100 kcal/d during cold (102 ± 47 kcal/d). Conclusion: The level of sympathetic innervation, as determined by 11 C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of 11 C-HED RI and 18 F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and 18 F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

SIFamide in the brain of the sphinx moth, Manduca sexta.

PubMed

Heuer, C M; Binzer, Marlene; Schachtner, J

2012-01-01

SIFamides form a group of highly conserved neuropeptides in insects, crustaceans, and chelicerates. Beyond their biochemical commonalities, the neuroanatomical distribution of SIFamide in the insect nervous system also shows a remarkable degree of conservation. Thus, expression of SIFamide has been found to be restricted to four neurons of the pars intercerebralis in different holometabolous species. By means of immunohistological stainings, we here show that in Manduca sexta, those four cells are complemented by additional immunoreactive cells located in the vicinity of the mushroom body calyx. Immunopositive processes form arborizations throughout the brain, innervating major neuropils like the antennal lobes, the central complex, and the optic neuropils.

RGS2 is a feedback inhibitor of melatonin production in the pineal gland

PubMed Central

Matsuo, Masahiro; Coon, Steven L.; Klein, David C.

2014-01-01

The 24-h rhythmic production of melatonin by the pineal gland is essential for coordinating circadian physiology. Melatonin production increases at night in response to the release of norepinephrine from sympathetic nerve processes which innervate the pineal gland. This signal is transduced through G-protein-coupled adrenergic receptors. Here, we found that the abundance of regulator of G-protein signaling 2 (RGS2) increases at night, that expression is increased by norepinephrine and that this protein has a negative feedback effect on melatonin production. These data are consistent with the conclusion that RGS2 functions on a daily basis to negatively modulate melatonin production. PMID:23523917

Motor neurons with limb-innervating character in the cervical spinal cord are sculpted by apoptosis based on the Hox code in chick embryo.

PubMed

Mukaigasa, Katsuki; Sakuma, Chie; Okada, Tomoaki; Homma, Shunsaku; Shimada, Takako; Nishiyama, Keiji; Sato, Noboru; Yaginuma, Hiroyuki

2017-12-15

In the developing chick embryo, a certain population of motor neurons (MNs) in the non-limb-innervating cervical spinal cord undergoes apoptosis between embryonic days 4 and 5. However, the characteristics of these apoptotic MNs remain undefined. Here, by examining the spatiotemporal profiles of apoptosis and MN subtype marker expression in normal or apoptosis-inhibited chick embryos, we found that this apoptotic population is distinguishable by Foxp1 expression. When apoptosis was inhibited, the Foxp1 + MNs survived and showed characteristics of lateral motor column (LMC) neurons, which are of a limb-innervating subtype, suggesting that cervical Foxp1 + MNs are the rostral continuation of the LMC. Knockdown and misexpression of Foxp1 did not affect apoptosis progression, but revealed the role of Foxp1 in conferring LMC identity on the cervical MNs. Furthermore, ectopic expression of Hox genes that are normally expressed in the brachial region prevented apoptosis, and directed Foxp1 + MNs to LMC neurons at the cervical level. These results indicate that apoptosis in the cervical spinal cord plays a role in sculpting Foxp1 + MNs committed to LMC neurons, depending on the Hox expression pattern. © 2017. Published by The Company of Biologists Ltd.

The Electrophysiology of Electric Organs of Marine Electric Fishes

PubMed Central

Bennett, M. V. L.; Wurzel, M.; Grundfest, H.

1961-01-01

Single electroplaques of Torpedo nobiliana have been studied with microelectrode recording. Direct evidence is presented that the only electrogenically reactive membrane of the cells is on the innervated surface and that this membrane is electrically inexcitable. Responses are not evoked by depolarizing currents applied to this membrane, but only by stimulating the innervating nerve fibers. The responses arise after a latency of 1 to 3 msec. This latency is not affected by large depolarizing or hyperpolarizing changes in membrane potential. Various properties that have been theoretically associated with electrically inexcitable responses have been also demonstrated to occur in the electroplaques. The neurally evoked response is not propagated actively in the membrane and may have different amplitudes and forms in closely adjacent regions. The maximal responses frequently are slightly larger than the recorded resting potential but the apparent small overshoot may be due to difficulty in recording the full resting potential. The responses are subject to electrochemical gradation and appear inverted in sign on applying strong outward currents across the innervated membrane. This membrane is cholinoceptive and shows marked desensitization. The membrane of the uninnervated surface has a very low resistance, a factor that aids maximum output of current during the discharge of the electric organ. PMID:19873534

Nikolaus Rüdinger (1832-1896), His Description of Joint Innervation in 1857, and the History of Surgical Joint Denervation.

PubMed

Gohritz, Andreas; Kaiser, Erich; Guggenheim, Merlin; Dellon, Arnold Lee

2018-01-01

 Selective joint denervation has become a reliable palliative treatment, especially for painful joints in the upper and lower extremity.  This article highlights the life and work of Nikolaus Rüdinger (1832-1896) who first described joint innervation which became the basis of later techniques of surgical joint denervation. The historical evolution of this method is outlined.  Rüdinger made a unique career from apprentice barber to military surgeon and anatomy professor in Munich, Germany. His first description of articular innervation of temporomandibular, shoulder, elbow, wrist, finger, sacroiliac, hip, knee, ankle, foot, and toe joints in 1857 stimulated the subsequent history of surgical joint denervation. Comparing his investigations with modern joint denervation methods, developed by pioneers like Albrecht Wilhelm or A. Lee Dellon, shows his great exactitude and anatomical correspondence despite different current terminology. Clinical series of modern surgical joint denervations reveal success rates of up to 80% with reliable long-term results.  The history of joint denervation with Rüdinger as its important protagonist offers inspiring insights into the evolution of surgical techniques and exemplifies the value of descriptive functional anatomy, even if surgical application may not have been realized until a century later. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves].

PubMed

Julé, Y

1975-05-01

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.

Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell function

PubMed Central

Rodriguez-Diaz, Rayner; Dando, Robin; Jacques-Silva, M. Caroline; Fachado, Alberto; Molina, Judith; Abdulreda, Midhat; Ricordi, Camillo; Roper, Stephen D.; Berggren, Per-Olof; Caicedo, Alejandro

2011-01-01

Acetylcholine is a neurotransmitter that plays a major role in the function of the insulin secreting pancreatic beta cell1,2. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species1,3,4, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of the human islet provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. We anticipate these results to revise models about neural input and cholinergic signaling in the endocrine pancreas. Cholinergic signaling within the islet represents a potential therapeutic target in diabetes5, highlighting the relevance of this advance to future drug development. PMID:21685896

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

PubMed

Stimpson, Cheryl D; Barger, Nicole; Taglialatela, Jared P; Gendron-Fitzpatrick, Annette; Hof, Patrick R; Hopkins, William D; Sherwood, Chet C

2016-03-01

Humans' closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Pharyngeal arch deficiencies affect taste bud development in the circumvallate papilla with aberrant glossopharyngeal nerve formation.

PubMed

Okubo, Tadashi; Takada, Shinji

2015-07-01

The pharyngeal arches (PAs) generate cranial organs including the tongue. The taste placodes, formed in particular locations on the embryonic tongue surface, differentiate into taste buds harbored in distinct gustatory papillae. The developing tongue also has a complex supply of cranial nerves through each PA. However, the relationship between the PAs and taste bud development is not fully understood. Ripply3 homozygous mutant mice, which have impaired third/fourth PAs, display a hypoplastic circumvallate papilla and lack taste buds, although the taste placode is normally formed. Formation of the glossopharyngeal ganglia is defective and innervation toward the posterior tongue is completely missing in Ripply3 mutant embryos at E12.5. Moreover, the distribution of neuroblasts derived from the epibranchial placode is severely, but not completely, atenuated, and the neural crest cells are diminished in the third PA region of Ripply3 mutant embryos at E9.5-E10.5. In Tbx1 homozygous mutant embryos, which exhibit another type of deficiency in PA development, the hypoplastic circumvallate papilla is observed along with abnormal formation of the glossopharyngeal ganglia and severely impaired innervation. PA deficiencies affect multiple aspects of taste bud development, including formation of the cranial ganglia and innervation to the posterior tongue. © 2015 Wiley Periodicals, Inc.

The visceromotor and somatic afferent nerves of the penis.

PubMed

Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

2015-05-01

Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

Compound Motor Action Potential Quantifies Recurrent Laryngeal Nerve Innervation in a Canine Model.

PubMed

Bhatt, Neel K; Park, Andrea M; Al-Lozi, Muhammad; Paniello, Randal C

2016-07-01

The compound motor action potential (CMAP) is the summated action potential from multiple muscle fibers activated by a single nerve impulse. The utility of laryngeal muscle CMAP for quantifying innervation following recurrent laryngeal nerve (RLN) injury was investigated. In a series of 21 canine hemi-laryngeal preparations, RLNs were exposed and a stimulating electrode placed. Maximum CMAP amplitudes and area under the curve from the thyroarytenoid (TA) muscles were obtained at baseline and at 6 months following injury to the RLN. Injury mechanisms included crush, stretch, cautery, and complete transection with microsuture repair. Prior to injury, baseline CMAP amplitudes and area under the curve were 15.81 mV and 15.49mVms, respectively. Six months following injury, CMAP amplitude and area under curve were 105.1% and 102.1% of baseline for stretch, 98.7% and 112.7% for crush, 93.3% and 114.3% for cautery. The CMAP amplitude and area under the curve in the transection/repair group had a 54.3% and 69.4% recovery, respectively, which were significantly different than baseline (P < .01, P < .05). These values were correlated with vocal fold motion. The CMAP is a measure of vocal fold innervation. The technique could be further developed for clinical and experimental applications. © The Author(s) 2016.

Mesodermal and neuronal retinoids regulate the induction and maintenance of limb innervating spinal motor neurons.

PubMed

Ji, Sheng-Jian; Zhuang, BinQuan; Falco, Crystal; Schneider, André; Schuster-Gossler, Karin; Gossler, Achim; Sockanathan, Shanthini

2006-09-01

During embryonic development, the generation, diversification and maintenance of spinal motor neurons depend upon extrinsic signals that are tightly regulated. Retinoic acid (RA) is necessary for specifying the fates of forelimb-innervating motor neurons of the Lateral Motor Column (LMC), and the specification of LMC neurons into medial and lateral subtypes. Previous studies implicate motor neurons as the relevant source of RA for specifying lateral LMC fates at forelimb levels. However, at the time of LMC diversification, a significant amount of retinoids in the spinal cord originates from the adjacent paraxial mesoderm. Here we employ mouse genetics to show that RA derived from the paraxial mesoderm is required for lateral LMC induction at forelimb and hindlimb levels, demonstrating that mesodermally synthesized RA functions as a second source of signals to specify lateral LMC identity. Furthermore, reduced RA levels in postmitotic motor neurons result in a decrease of medial and lateral LMC neurons, and abnormal axonal projections in the limb; invoking additional roles for neuronally synthesized RA in motor neuron maintenance and survival. These findings suggest that during embryogenesis, mesodermal and neuronal retinoids act coordinately to establish and maintain appropriate cohorts of spinal motor neurons that innervate target muscles in the limb.

A fine-structural survey of the pulpal innervation in the rat mandibular incisor.

PubMed

Bishop, M A

1981-02-01

The innervation of the rat incisor pulp has been studied using transmission electron microscopy and light microscopy. Transverse sections of mandibular incisor pulp (380-460 gm rats) from numerous positions in the long axis of the tooth were examined systematically in the electron microscopy. Quantitative data on total axon populations were obtained. The nerve fibers were found to pass through the lingual half of the pulp from the apical end to within 2 mm of the incisal tip. Although the nerve fibers were seen to lie amongst the connective tissue cells between the blood vessels, the electron microscopic observations showed that the blood vessels are not innervated. Throughout their pulpal course the nerve fibers showed no trace of perineurial investment. Virtually all the axons were unmyelinated. Total numbers of axons were small (233-328) and peak diameters of 0.3-0.4 microM confirmed the observed immature appearance of the nerve supply. Obvious nerve endings were seldom observed and the axons showed no structural association with odontoblasts. The evidence indicates that, although most axons terminate near the incisal end of the tooth, no specific structure is supplied. The qualitative features of the axons do not suggest autonomic function; however, they are consistent with a sensory role.

Comparative histology of the adult electric organ among four species of the genus Campylomormyrus (Teleostei: Mormyridae).

PubMed

Paul, Christiane; Mamonekene, Victor; Vater, Marianne; Feulner, Philine G D; Engelmann, Jacob; Tiedemann, Ralph; Kirschbaum, Frank

2015-04-01

The electric organ (EO) of weakly electric mormyrids consists of flat, disk-shaped electrocytes with distinct anterior and posterior faces. There are multiple species-characteristic patterns in the geometry of the electrocytes and their innervation. To further correlate electric organ discharge (EOD) with EO anatomy, we examined four species of the mormyrid genus Campylomormyrus possessing clearly distinct EODs. In C. compressirostris, C. numenius, and C. tshokwe, all of which display biphasic EODs, the posterior face of the electrocytes forms evaginations merging to a stalk system receiving the innervation. In C. tamandua that emits a triphasic EOD, the small stalks of the electrocyte penetrate the electrocyte anteriorly before merging on the anterior side to receive the innervation. Additional differences in electrocyte anatomy among the former three species with the same EO geometry could be associated with further characteristics of their EODs. Furthermore, in C. numenius, ontogenetic changes in EO anatomy correlate with profound changes in the EOD. In the juvenile the anterior face of the electrocyte is smooth, whereas in the adult it exhibits pronounced surface foldings. This anatomical difference, together with disparities in the degree of stalk furcation, probably contributes to the about 12 times longer EOD in the adult.

[Change in trigeminal mesencephalic neurons after teeth extraction in guinea pig].

PubMed

Kimoto, A

1993-03-01

Trigeminal mesencephalic (Mes V) neurons innervating the periodontal mechanoreceptor (PMR) are known to play an important role in controlling the bite force and jaw-movements during mastication. After teeth loss, the PMR disappears due to loss of the periodontal membrane. The present work is a study on whether cell death is induced in the Mes V neurons in association with teeth loss. The upper and lower incisors were extracted on the right side in 5 guinea pigs (extraction group) and the other 5 guinea pigs were kept intact (control group). In the extraction group, the animals were kept alive for 58-119 days after teeth extraction. Serial coronal sections (50 microns thick) were made of the midbrain and pons and stained with cresyl violet. The Mes V neurons were counted on every other section. In the caudal half of the Mes V nucleus, where the neurons innervating the PMR are reported to be located, the number of neurons was less on the right side than on the left side (P < 0.01) in the extraction group, while there was no difference between the right and left sides in the control group. We conclude that teeth extraction can induce cell death in the Mes V neurons innervating the PMR and produce a significant change in the brainstem mechanisms controlling mastication.

Effects of Oxaliplatin Treatment on the Myenteric Plexus Innervation and Glia in the Murine Distal Colon.

PubMed

Stojanovska, Vanesa; McQuade, Rachel M; Miller, Sarah; Nurgali, Kulmira

2018-05-01

Oxaliplatin (platinum-based chemotherapeutic agent) is a first-line treatment of colorectal malignancies; its use associates with peripheral neuropathies and gastrointestinal side effects. These gastrointestinal dysfunctions might be due to toxic effects of oxaliplatin on the intestinal innervation and glia. Male Balb/c mice received intraperitoneal injections of sterile water or oxaliplatin (3 mg/kg/d) triweekly for 2 weeks. Colon tissues were collected for immunohistochemical assessment at day 14. The density of sensory, adrenergic, and cholinergic nerve fibers labeled with calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and vesicular acetylcholine transporter (VAChT), respectively, was assessed within the myenteric plexus of the distal colon. The number and proportion of excitatory neurons immunoreactive (IR) against choline acetyltransferase (ChAT) were counted, and the density of glial subpopulations was determined by using antibodies specific for glial fibrillary acidic protein (GFAP) and s100β protein. Oxaliplatin treatment induced significant reduction of sensory and adrenergic innervations, as well as the total number and proportion of ChAT-IR neurons, and GFAP-IR glia, but increased s100β expression within the myenteric plexus of the distal colon. Treatment with oxaliplatin significantly alters nerve fibers and glial cells in the colonic myenteric plexus, which could contribute to long-term gastrointestinal side effects following chemotherapeutic treatment.

Neuromuscular plasticity in the locust after permanent removal of an excitatory motoneuron of the extensor tibiae muscle.

PubMed

Büschges, A; Djokaj, S; Bässler, D; Bässler, U; Rathmayer, W

2000-01-01

The capacity of the larval insect nervous system to compensate for the permanent loss of one of the two excitatory motoneurons innervating a leg muscle was investigated in the locust (Locusta migratoria). In the fourth instar, the fast extensor tibiae (FETi) motoneuron in the mesothoracic ganglion was permanently removed by photoinactivation with a helium-cadmium laser. Subsequently, the animals were allowed to develop into adulthood. When experimental animals were tested as adults after final ecdysis, fast-contracting fibers in the most proximal region of the corresponding extensor muscle, which are normally predominantly innervated by FETi only, uniformly responded to activity of the slow extensor tibiae (SETi) neuron. In adult operated animals, single pulses to SETi elicited large junctional responses in the fibers which resulted in twitch contractions of these fibers similar to the responses to FETi activity in control animals. The total number of muscle fibers, their properties as histochemically determined contractional types (fast and slow), and their distribution were not affected by photoinactivation of FETi. Possible mechanisms enabling the larval neuromuscular system to compensate for the loss of FETi through functionally similar innervation by a different motoneuron, i.e. SETi, are discussed. Copyright 2000 John Wiley & Sons, Inc.

Spatial orientation of semicircular canals and afferent sensitivity vectors in pigeons

NASA Technical Reports Server (NTRS)

Dickman, J. D.

1996-01-01

Rotational head motion in vertebrates is detected by the semicircular canal system, whose innervating primary afferent fibers carry information about movement in specific head planes. The semicircular canals have been qualitatively examined over a number of years, and the canal planes have been quantitatively characterized in several animal species. The present study first determined the geometric relationship between individual semicircular canals and between the canals and the stereotactic head planes in pigeons. Stereotactic measurements of multiple points along the circumference of the bony canals were taken, and the measured points fitted with a three-dimensional planar surface. Direction normals to the plane's surface were calculated and used to define angles between semicircular canal pairs. Because of the unusual shape of the anterior semicircular canals in pigeons, two planes, a major and a minor, were fitted to the canal's course. Calculated angle values for all canals indicated that the horizontal and posterior semicircular canals are nearly orthogonal, but the anterior canals have substantial deviations from orthogonality with other canal planes. Next, the responses of the afferent fibers that innervate each of the semicircular canals to 0.5 Hz sinusoidal rotation about an earth-vertical axis were obtained. The head orientation relative to the rotation axis was systematically varied so that directions of maximum sensitivity for each canal afferent could be determined. These sensitivity vectors were then compared with the canal plane direction normals. The afferents that innervated specific semicircular canals formed homogeneous clusters of sensitivity vectors in different head planes. The horizontal and posterior afferents had average sensitivity vectors that were largely co-incident with the innervated canal plane direction normals. Anterior canal afferents, however, appeared to synthesize contributions from the major and minor plane components of the bony canal structure to produce a resultant sensitivity vector that was positioned between the canal planes. Calculated angles between the average canal afferent sensitivity vectors revealed that direction orthogonality is preserved at the afferent signal level, even though deviations from canal plane orthogonality exist.

Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

PubMed

Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

2015-12-01

Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Postnatal development of autonomic and sensory innervation of thoracic hairy skin in the rat. A histochemical, immunocytochemical, and radioenzymatic study.

PubMed

Schotzinger, R J; Landis, S C

1990-05-01

Histochemical, immunocytochemical, and radioenzymatic techniques were used to examine the neurotransmitter-related properties of the innervation of thoracic hairy skin in rats during adulthood and postnatal development. In the adult, catecholamine-containing fibers were associated with blood vessels and piloerector muscles, and ran in nerve bundles throughout the dermis. The distribution of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers was identical. Neuronal fibers displaying neuropeptide Y (NPY) immunoreactivity were seen in association with blood vessels. Double-labeling studies suggested that most, if not all, NPY-IR fibers were also TH-IR and likewise most, if not all, vessel-associated TH-IR fibers were also NPY-IR. Calcitonin gene-related peptide (CGRP)-IR fibers were observed near and penetrating into the epidermis, in close association with hair follicles and blood vessels, and in nerve bundles. A similar distribution of substance P (SP)-IR fibers was evident. In adult animals treated as neonates with the sympathetic neurotoxin 6-hydroxydopamine, a virtual absence of TH-IR and NPY-IR fibers was observed, whereas the distribution of CGRP-IR and SP-IR fibers appeared unaltered. During postnatal development, a generalized increase in the number, fluorescence intensity, and varicose morphology of neuronal fibers displaying catecholamine fluorescence, NPY-IR, CGRP-IR, and SP-IR was observed. By postnatal day 21, the distribution of the above fibers had reached essentially adult levels, although the density of epidermal-associated CGRP-IR and SP-IR fibers was significantly greater than in the adult. The following were not evident in thoracic hairy skin at any timepoint examined: choline acetyltransferase activity, acetylcholinesterase histochemical staining or immunoreactivity, fibers displaying immunoreactivity to vasoactive intestinal peptide, cholecystokinin, or leucine-enkephalin. The present study demonstrates that the thoracic hairy skin in developing and adult rats receives an abundant sympathetic catecholaminergic and sensory innervation, but not a cholinergic innervation.