Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

PubMed Central

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

2015-01-01

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

PubMed Central

Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

2006-01-01

Glutamate acts at central synapses via ionotropic (iGluR – NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed. PMID:16945965

Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors.

PubMed

Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

2006-11-15

Glutamate acts at central synapses via ionotropic (iGluR--NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed.

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

PubMed

Lundberg, J M; Brodin, E; Saria, A

1983-11-01

The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves

Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation

PubMed Central

Biddinger, Jessica E.; Baquet, Zachary C.; Jones, Kevin R.; McAdams, Jennifer

2013-01-01

A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout (SM-NT-3KO) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3KO mice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3KO mice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3KO mice compared with controls. The increases in meal duration and first meal size of SM-NT-3KO mice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation. PMID:24068045

The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

PubMed

Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

2014-07-01

It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

Central vagal sensory and motor connections: human embryonic and fetal development.

PubMed

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

PubMed

Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

2015-12-01

Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

PubMed

Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

2017-08-01

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

Serotonin and cholecystokinin synergistically stimulate rat vagal primary afferent neurones

PubMed Central

Li, Y; Wu, X Y; Owyang, C

2004-01-01

Recent studies indicate that cholecystokinin (CCK) and serotonin (5-hydroxytryptamine, 5-HT) act via vagal afferent fibres to mediate gastrointestinal functions. In the present study, we characterized the interaction between CCK and 5-HT in the vagal primary afferent neurones. Single neuronal discharges of vagal primary afferent neurones innervating the duodenum were recorded from rat nodose ganglia. Two groups of nodose ganglia neurones were identified: group A neurones responded to intra-arterial injection of low doses of cholecystokinin octapeptide (CCK-8; 10–60 pmol); group B neurones responded only to high doses of CCK-8 (120–240 pmol), and were also activated by duodenal distention. CCK-JMV-180, which acts as an agonist in high-affinity states and as an antagonist in low-affinity states, dose dependently stimulated group A neurones, but inhibited the effect of the high doses of CCK-8 on group B neurones. Duodenal perfusion of 5-HT evoked dose-dependent increases in nodose neuronal discharges. Some neurones that responded to 5-HT showed no response to either high or low doses of CCK-8. A separate group of nodose neurones that possessed high-affinity CCK type A (CCK-A) receptors also responded to luminal infusion of 5-HT. Further, a subthreshold dose of CCK-8 (i.e. 5 pmol) produced no measurable electrophysiological effects but it augmented the neuronal responses to 5-HT. This potentiation effect of CCK-8 was eliminated by CR 1409. From these results we concluded that the vagal nodose ganglion contains neurones that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurones that express high-affinity CCK-A receptors also express 5-HT3 receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. PMID:15235095

Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

PubMed Central

Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

2012-01-01

Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

PubMed Central

Biddinger, Jessica E.; Fox, Edward A.

2010-01-01

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

PubMed

Biddinger, Jessica E; Fox, Edward A

2010-08-04

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

PubMed

Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

1995-02-15

It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat

PubMed Central

Zhou, Shi-Yi; Lu, Yuan-Xu; Owyang, Chung

2011-01-01

Hyperglycemia has a profound effect on gastric motility. However, little is known about site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg dL−1 had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg dL−1), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g kg−1) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-L-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia, and in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation. PMID:18356537

Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

PubMed

Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W

2016-12-01

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology

PubMed Central

Browning, Kirsteen N.

2015-01-01

Vagal neurocircuits are vitally important in the co-ordination and modulation of GI reflexes and homeostatic functions. 5-hydroxytryptamine (5-HT; serotonin) is critically important in the regulation of several of these autonomic gastrointestinal (GI) functions including motility, secretion and visceral sensitivity. While several 5-HT receptors are involved in these physiological responses, the ligand-gated 5-HT3 receptor appears intimately involved in gut-brain signaling, particularly via the afferent (sensory) vagus nerve. 5-HT is released from enterochromaffin cells in response to mechanical or chemical stimulation of the GI tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents. 5-HT3 receptors are also present on the soma of vagal afferent neurons, including GI vagal afferent neurons, where they can be activated by circulating 5-HT. The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem. While activation of central brainstem 5-HT3 receptors modulates visceral functions, it is still unclear whether central vagal neurons, i.e., nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) neurons themselves also display functional 5-HT3 receptors. Thus, activation of 5-HT3 receptors may modulate the excitability and activity of gastrointestinal vagal afferents at multiple sites and may be involved in several physiological and pathophysiological conditions, including distention- and chemical-evoked vagal reflexes, nausea, and vomiting, as well as visceral hypersensitivity. PMID:26578870

Role of the vagus nerve in the development and treatment of diet‐induced obesity

PubMed Central

2016-01-01

Abstract This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie‐rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high‐fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade‐induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity. PMID:26959077

Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

PubMed

Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

2016-10-15

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

PubMed Central

Kember, Guy; Ardell, Jeffrey L.; Armour, John A.; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity. PMID:25479368

Vagal nerve stimulation therapy: what is being stimulated?

PubMed

Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.

PubMed

Suarez, Andrea N; Hsu, Ted M; Liu, Clarissa M; Noble, Emily E; Cortella, Alyssa M; Nakamoto, Emily M; Hahn, Joel D; de Lartigue, Guillaume; Kanoski, Scott E

2018-06-05

The vagus nerve is the primary means of neural communication between the gastrointestinal (GI) tract and the brain. Vagally mediated GI signals activate the hippocampus (HPC), a brain region classically linked with memory function. However, the endogenous relevance of GI-derived vagal HPC communication is unknown. Here we utilize a saporin (SAP)-based lesioning procedure to reveal that selective GI vagal sensory/afferent ablation in rats impairs HPC-dependent episodic and spatial memory, effects associated with reduced HPC neurotrophic and neurogenesis markers. To determine the neural pathways connecting the gut to the HPC, we utilize monosynaptic and multisynaptic virus-based tracing methods to identify the medial septum as a relay connecting the medial nucleus tractus solitarius (where GI vagal afferents synapse) to dorsal HPC glutamatergic neurons. We conclude that endogenous GI-derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem-septal pathway, thereby identifying a previously unknown role for the gut-brain axis in memory control.

Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

PubMed

Prabhakar, N R; Runold, M; Yamamoto, Y; Lagercrantz, H; Cherniack, N S; von Euler, C

1987-09-01

Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

Intraoperative monitoring of the recurrent laryngeal nerve by vagal nerve stimulation in thyroid surgery.

PubMed

Farizon, Brigitte; Gavid, Marie; Karkas, Alexandre; Dumollard, Jean-Marc; Peoc'h, Michel; Prades, Jean-Michel

2017-01-01

The aim of the present study was to evaluate the thyroarytenoid muscle response during bilateral thyroid surgery using vagal nerve stimulation. 195 patients (390 nerves at risk) underwent a total thyroidectomy. The recurrent laryngeal nerve's function was checked by analyzing the amplitude and the latency of the thyroarytenoid muscle's responses after a vagal nerve's stimulation (0.5 and 1 mA) using the NIM3 Medtronic system. All patients were submitted to preoperative and postoperative laryngoscopy. 20 patients get no thyroarytenoid muscle response to the vagal nerve stimulation, and 14 postoperative recurrent laryngeal nerve palsies were confirmed (3.8 %). Two palsies were present after 6 months (0.51 %). All the patients with muscle's response have normal mobility vocal fold. The test sensitivity was 100 % and the test specificity was 98 %. Physiologically, the mean latencies of the muscular potentials for the right RLN were, respectively, 3.89 and 3.83 ms (p > 0.05) for the stimulation at 0.5 and 1 mA. The mean latencies for the left RLN were, respectively, 6.25 and 6.22 ms for the stimulation at 0.5 and 1 mA (p > 0.05). The difference of the latencies between the right and the left nerve was 2.30 ms (1.75-3.25 ms) with a stimulation of 0.5 or 1 mA (p < 0.05). Thyroarytenoid muscle's response via a vagal nerve stimulation showed a functional asymmetry of the laryngeal adduction with a faster right response. Surgically, this method can predict accurately an immediate postoperative vocal folds function in patients undergoing a bilateral thyroid surgery.

Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

PubMed

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-03-16

Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs

PubMed Central

Mazzone, Stuart B; Mori, Nanako; Canning, Brendan J

2005-01-01

Cough initiated from the trachea and larynx in anaesthetized guinea-pigs is mediated by capsaicin-insensitive, mechanically sensitive vagal afferent neurones. Tachykinin-containing, capsaicin-sensitive C-fibres also innervate the airways and have been implicated in the cough reflex. Capsaicin-sensitive nerves act centrally and synergistically to modify reflex bronchospasm initiated by airway mechanoreceptor stimulation. The hypothesis that polymodal mechanoreceptors and capsaicin-sensitive afferent nerves similarly interact centrally to regulate coughing was addressed in this study. Cough was evoked from the tracheal mucosa either electrically (16 Hz, 10 s trains, 1–10 V) or by citric acid (0.001–2 m). Neither capsaicin nor bradykinin evoked a cough when applied to the trachea of anaesthetized guinea-pigs, but they substantially reduced the electrical threshold for initiating the cough reflex. The TRPV1 receptor antagonist capsazepine prevented the increased cough sensitivity induced by capsaicin. These effects of topically applied capsaicin and bradykinin were not due to interactions between afferent nerve subtypes within the tracheal wall or a direct effect on the cough receptors, as they were mimicked by nebulizing 1 mg ml−1 bradykinin into the lower airways and by microinjecting 0.5 nmol capsaicin into nucleus of the solitary tract (nTS). Citric acid-induced coughing was also potentiated by inhalation of bradykinin. The effects of tracheal capsaicin challenge on cough were mimicked by microinjecting substance P (0.5–5 nmol) into the nTS and prevented by intracerebroventricular administration (20 nmol h−1) of the neurokinin receptor antagonists CP99994 or SB223412. Tracheal application of these antagonists was without effect. C-fibre activation may thus sensitize the cough reflex via central mechanisms. PMID:16051625

A bioinspired flexible organic artificial afferent nerve

NASA Astrophysics Data System (ADS)

Kim, Yeongin; Chortos, Alex; Xu, Wentao; Liu, Yuxin; Oh, Jin Young; Son, Donghee; Kang, Jiheong; Foudeh, Amir M.; Zhu, Chenxin; Lee, Yeongjun; Niu, Simiao; Liu, Jia; Pfattner, Raphael; Bao, Zhenan; Lee, Tae-Woo

2018-06-01

The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.

Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone

PubMed Central

Holmes, Gregory M; Browning, Kirsteen N; Babic, Tanja; Fortna, Samuel R; Coleman, F Holly; Travagli, R Alberto

2013-01-01

Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and reduced by l-NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic-mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric-projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT-induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit. PMID:23587885

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.

PubMed

Shanks, Julia; Xia, Zhiqiu; Lisco, Steven J; Rozanski, George J; Schultz, Harold D; Zucker, Irving H; Wang, Han-Jun

2018-06-01

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory

Resting afferent renal nerve discharge and renal inflammation: Elucidating the role of afferent and efferent renal nerves in DOCA-salt hypertension

PubMed Central

Banek, Christopher T.; Knuepfer, Mark M.; Foss, Jason D.; Fiege, Jessica K.; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W.

2016-01-01

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity (RSNA) has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA)-salt rat model. Uninephrectomized male Sprague Dawley rats (275–300g) underwent selective afferent-selective RDNx (A-RDNx; n=10), total RDNx (T-RDNx; n=10), or Sham (n=10) and were instrumented for measurement of mean arterial pressure (MAP) and heart rate (HR) by radiotelemetry. Rats received 100mg DOCA (s.c.) and 0.9% saline for 21 days. Resting afferent renal nerve activity (ARNA) in DOCA and Vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting ARNA, expressed as a percent of peak afferent nerve activity (%Amax), was substantially increased in DOCA vs. Vehicle (35.8±4.4 vs. 15.3±2.8%Amax). The DOCA-Sham hypertension (132±12 mmHg) was attenuated by ~50% in both T-RDNx (111±8) and A-RDNx (117±5mmHg) groups. Renal inflammation induced by DOCA-salt was attenuated by T-RDNx, and unaffected by A-RDNx. These data suggest ARNA may mediate the hypertensive response to DOCA-salt, but inflammation may be mediated primarily by efferent RSNA. Also, resting ARNA is elevated in DOCA-salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. PMID:27698066

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

PubMed

Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-Induced antihyperalgesia.

PubMed

Radhakrishnan, Rajan; Sluka, Kathleen A

2005-10-01

In this study we investigated the involvement of cutaneous versus knee joint afferents in the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by differentially blocking primary afferents with local anesthetics. Hyperalgesia was induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency to heat before and 4 hours after injection. Skin surrounding the inflamed knee joint was anesthetized using an anesthetic cream (EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed knee joint, and low or high frequency TENS was applied. Control experiments were done using vehicles. In control and EMLA groups, both low and high frequency TENS completely reversed hyperalgesia. However, injection of lidocaine into the knee joint prevented antihyperalgesia produced by both low and high frequency TENS. Recordings of cord dorsum potentials showed that both low and high frequency TENS at sensory intensity activates only large diameter afferent fibers. Increasing intensity to twice the motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both high and low frequency TENS, confirming a loss of large diameter primary afferent input after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous afferents, prevents the antihyperalgesia effects of TENS. We conclude that large diameter primary afferent fibers from deep tissue are required and that activation of cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous afferent activation. In this study by

Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice.

PubMed

Urata, Tomomi; Mori, Noriyuki; Fukuwatari, Tsutomu

2017-05-22

Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation. We found that intragastric administration of 1,8-cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these responses. Intravenous administration of 1,8-cineole also showed similar effects. In vagotomized mice, the responses induced by intragastric administration of 1,8-cineole were attenuated. These results suggest that TRPM8 expressed in tissues apart from cutaneous sensory nerves are involved in autonomic thermoregulation response. Copyright © 2017 Elsevier B.V. All rights reserved.

OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

PubMed

Collins, Valerie M; Daly, Donna M; Liaskos, Marina; McKay, Neil G; Sellers, Donna; Chapple, Christopher; Grundy, David

2013-11-01

To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures. Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release. These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves. © 2013 The Authors. BJU International © 2013 BJU International.

Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms.

PubMed

Faris, Patricia L; Eckert, Elke D; Kim, Suck-Won; Meller, William H; Pardo, Jose V; Goodale, Robert L; Hartman, Boyd K

2006-05-01

The bilateral vagus nerves (Cranial X) provide both afferent and efferent connections between the viscera and the caudal medulla. The afferent branches increasingly are being recognized as providing significant input to the central nervous system for modulation of complex behaviors. In this paper, we review evidence from our laboratory that increases in vagal afferent activity are involved in perpetuating binge-eating and vomiting in bulimia nervosa. Preliminary findings are also presented which suggest that a subgroup of depressions may have a similar pathophysiology. Two main approaches were used to study the role of vagal afferents. Ondansetron (ONDAN), a 5-HT3 antagonist, was used as a pharmacological tool for inhibiting or reducing vagal afferent neurotransmission. Second, somatic pain detection thresholds were assessed for monitoring a physiological process known to be modulated by vagal afferents, including the gastric branches involved in meal termination and satiety. High levels of vagal activity result in an increase in pain detection thresholds. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Positron Emission Tomography (PET) was used to identify higher cortical brain areas activated by vagal stimulation produced by proximal gastric distention in normal eating subjects. Double-blind treatment of severe bulimia nervosa subjects with ONDAN resulted in a rapid and significant decrease in binge-eating and vomiting compared to placebo controls. The decrease in abnormal eating episodes was accompanied by a return of normal satiety. Pain detection thresholds measured weekly over the course of the treatment protocol were found to dynamically fluctuate in association with bulimic episodes. Thresholds were the most elevated during periods of short-term abstinence from the behaviors, suggesting that not engaging in a binge/vomit episode is accompanied by an increase in vagal activity. ONDAN also resulted in abolition of the

On the nature of the afferent fibers of oculomotor nerve.

PubMed

Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

1989-03-01

The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

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

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.

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Pharmacology of Vagal Afferent Influences on Disordered Breathing During Sleep

PubMed Central

Carley, David W; Radulovacki, Miodrag

2008-01-01

Sleep related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of ∼2% of women and ∼4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved. PMID:18694851

Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

PubMed Central

Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

2010-01-01

After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

PubMed

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

1987-12-01

Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

Different role of TTX-sensitive voltage-gated sodium channel (NaV 1) subtypes in action potential initiation and conduction in vagal airway nociceptors.

PubMed

Kollarik, M; Sun, H; Herbstsomer, R A; Ru, F; Kocmalova, M; Meeker, S N; Undem, B J

2018-04-15

The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (Na V 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective Na V 1.7 blockers. The difference between the initiation of action potentials within the airways vs. conduction along the axons should be considered when developing Na V 1 blocking drugs for topical application to the respiratory tract. The action potential (AP) initiation in the nerve terminals and its subsequent AP conduction along the axons do not necessarily depend on the same subtypes of voltage-gated sodium channels (Na V 1s). We evaluated the role of TTX-sensitive and TTX-resistant Na V 1s in vagal afferent nociceptor nerves derived from jugular and nodose ganglia innervating the respiratory system. Single cell RT-PCR was performed on vagal afferent neurons retrogradely labelled from the guinea pig trachea. Almost all of the jugular neurons expressed the TTX-sensitive channel Na V 1.7 along with TTX-resistant Na V 1.8 and Na V 1.9. Tracheal nodose neurons also expressed Na V 1.7 but, less frequently, Na V 1.8 and Na V 1.9. Na V 1.6 were expressed in ∼40% of the jugular and 25% of nodose tracheal neurons. Other Na V 1 α subunits were only rarely expressed. Single fibre recordings were made from the vagal nodose and jugular nerve fibres innervating the trachea or lung in the isolated perfused vagally-innervated preparations that allowed for selective drug delivery to the nerve terminal compartment (AP initiation) or to the desheathed vagus nerve (AP conduction). AP initiation in

Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats

PubMed Central

Kirkup, Anthony J; Jiang, Wen; Bunnett, Nigel W; Grundy, David

2003-01-01

Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001–1 mg kg−1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg−1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg−1, I.V.), but not a cocktail of ω-conotoxins GVIA and SVIB (each at 25 μg kg−1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg−1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms. PMID:14561839

Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

PubMed Central

Breit, Sigrid; Kupferberg, Aleksandra; Rogler, Gerhard; Hasler, Gregor

2018-01-01

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms. PMID:29593576

Effects of stimulation of muscarinic receptors on bladder afferent nerves in the in vitro bladder-pelvic afferent nerve preparation of the rat.

PubMed

Yu, Yongbei; de Groat, William C

2010-11-18

Effects of a muscarinic receptor agonist oxotremorine-M (oxo-M) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced rhythmic bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 25 and 50 μM oxo-M significantly increased afferent firing from 41 ± 2 spikes/s to 51 ± 4 spikes/s and 60.5 ± 5 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. The afferent nerve firing induced by isotonic distension of the bladder (10-40 cmH(2)O) was increased 22-100% by intravesical administration of 50 μM oxo-M. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Oxo-M significantly decreased the voltage threshold by 40% (p<0.05) and increased by 157% (p<0.05) the area of the AP evoked at a submaximal stimulus intensity. These effects were blocked by intravesical injection of 5 μM atropine methyl nitrate (AMN). Intravesical administration of 5 μM AMN alone did not alter BAN firing or the amplitude of bladder contractions. The facilitatory effects induced by oxo-M on BAN activity were also suppressed (p<0.05) by intravesical administration of 2',3'-0-trinitrophenyl-ATP (TNP-ATP) (30 μM). In preparations pretreated with capsaicin (125 mg/kg, s.c.) the facilitatory effects of 50 μM oxo-M on BAN activity were absent. These results suggest that activation of muscarinic receptors facilitates mechano-sensitive, capsaicin-sensitive BAN activity in part by mechanisms involving purinergic receptors located near the luminal surface of the bladder and ATP release which presumably occurs in the urothelium. Copyright © 2010 Elsevier B.V. All rights reserved.

The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

PubMed

Nakamura, S I; Takahashi, K; Takahashi, Y; Yamagata, M; Moriya, H

1996-07-01

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

Effect of endogenous tachykinins on neuro-effector transmission of vagal nerve in guinea-pig tracheal tissue.

PubMed

Aizawa, H; Miyazaki, N; Inoue, H; Ikeda, T; Shigematsu, N

1990-01-01

To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10(-8) to 10(-7) M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10(-7) to 10(-6) M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10(-6) to 10(-5) M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig.

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge

PubMed Central

Schelegle, Edward S.; Walby, William F.

2012-01-01

Brown-Norway rats (n = 113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O3) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0 ppm O3 for 8 hours. There were three groups: 1) control; 2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and 3) vagotomy. O3 inhalation resulted in a significant increase in lung resistance (RL) and an exaggerated response to subsequent allergen challenge. PCT abolished the O3-induced increase in RL and significantly reduced the increase in RL induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O3 inhalation and subsequent challenge with allergen. In this model of O3 exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. PMID:22525484

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

PubMed

Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity ( P <0.05). The stress relaxed less in the diabetic intestinal segment ( P <0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.

PubMed

Schelegle, E S; Walby, W F; Mansoor, J K; Chen, A T

2001-05-01

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

PubMed Central

Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Background Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. PMID:29238211

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

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge.

PubMed

Schelegle, Edward S; Walby, William F

2012-05-31

Brown-Norway rats (n=113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O(3)) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0ppm O(3) for 8h. There were three groups: (1) control; (2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and (3) vagotomy. O(3) inhalation resulted in a significant increase in lung resistance (R(L)) and an exaggerated response to subsequent allergen challenge. PCT abolished the O(3)-induced increase in R(L) and significantly reduced the increase in R(L) induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O(3) inhalation and subsequent challenge with allergen. In this model of O(3) exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. Copyright © 2012 Elsevier B.V. All rights reserved.

Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

PubMed

Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

2015-04-01

Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

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.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus

Vagal nerve stimulator: Evolving trends

PubMed Central

Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

2013-01-01

Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig

PubMed Central

Lundberg, J. M.; Saria, A.; Brodin, E.; Rosell, S.; Folkers, K.

1983-01-01

Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After intravenous administration of a substance P (SP) antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP also reduced the increase in insufflation pressure caused by intravenous SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were, however, not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. The data suggest that a major portion of the vagally or capsaicin-induced increase in smooth muscle tone is caused by SP release from sensory neurons. In addition, activation of vagal SP-containing sensory nerves induces local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions. Images PMID:6189120

An indirect component in the evoked compound action potential of the vagal nerve.

PubMed

Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

2010-12-01

The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

Implications for bidirectional signaling between afferent nerves and urothelial cells-ICI-RS 2014.

PubMed

Kanai, Anthony; Fry, Christopher; Ikeda, Youko; Kullmann, Florenta Aura; Parsons, Brian; Birder, Lori

2016-02-01

To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed. It is clear that afferent-urothelial interactions are integral to the regulation of normal bladder function and that its disruption can have detrimental consequences. The urothelium is capable of releasing numerous signaling factors that can affect sensory neurons innervating the suburothelium. However, the understanding of how factors released from urothelial cells and afferent nerve terminals regulate one another is incomplete. Utilization of techniques such as viruses that genetically encode Ca(2+) sensors, based on calmodulin and green fluorescent protein, has helped to address the cellular mechanisms involved. Additionally, the epithelial-neuronal interactions in the urethra may also play a significant role in lower urinary tract regulation and merit further investigation. The signaling capabilities of the urothelium and afferent nerves are well documented, yet how these signals are integrated to regulate bladder function is unclear. There is unquestionably a need for expanded methodologies to further our understanding of lower urinary tract sensory mechanisms and their contribution to various pathologies. © 2016 Wiley Periodicals, Inc.

Immunomodulation of afferent neurons in guinea-pig isolated airway.

PubMed

Riccio, M M; Myers, A C; Undem, B J

1996-03-01

excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus may contribute to the pathophysiology of allergic airway diseases.

Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

PubMed

Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

1987-07-01

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

Rat isolated phrenic nerve-diaphragm preparation for pharmacological study of muscle spindle afferent activity: effect of oxotremorine.

PubMed Central

Ganguly, D K; Nath, D N; Ross, H G; Vedasiromoni, J R

1978-01-01

1. Muscle spindle afferent discharges exhibiting an approximately linear length-frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve-diaphragm preparation of the rat. 2. Muscle spindle afferent discharges could be identified by their characteristic "spindle pause" during muscle contraction and by their response to succinylcholine. 3. Cholinergic influence on spontaneous and stretch-induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)-Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles. 4. Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium-3 and (+)-tubocurarine failed to affect the rate of spontaneous and stretch-induced spindle discharges. 5. Oxotremorine markedly increased the rate of spontaneous and stretch-induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium-3 and (+)-tubocurarine. 6. These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents and hyperactive in Parkinsonian patients. PMID:151569

Validation and characterization of a novel method for selective vagal deafferentation of the gut.

PubMed

Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume

2017-10-01

There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. NEW & NOTEWORTHY We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions. Copyright © 2017 the American Physiological Society.

Disrupting vagal feedback affects birdsong motor control.

PubMed

Méndez, Jorge M; Dall'asén, Analía G; Goller, Franz

2010-12-15

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

Disrupting vagal feedback affects birdsong motor control

PubMed Central

Méndez, Jorge M.; Dall'Asén, Analía G.; Goller, Franz

2010-01-01

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback. PMID:21113000

Vagal Nerve Stimulator Malfunction with Change in Neck Position: Case Report and Literature Review.

PubMed

D'Agostino, Erin; Makler, Vyacheslav; Bauer, David F

2018-06-01

Vagal nerve stimulation is a safe and well-tolerated treatment for drug-resistant epilepsy. Complications and failure of the device can result from lead fracture, device malfunction, disconnection, or battery displacement and can result in a variety of symptoms. We present an interesting case of stimulator malfunction with increased impedance change seen only with a change in head position. The patient is a 25-year-old male with a vagal nerve stimulator (VNs) placed for medically refractory epilepsy who presented with neck pain and an electrical pulling sensation in his neck whenever he turned his head to the right. Initial interrogation of the VNs showed normal impedance. Subsequent interrogation with the patient's head turned found increased impedance only when the head was turned to the right. The patient had successful removal and replacement of the device with resolution of his preoperative complaints. Partial lead fracture was seen at explant. VNs malfunction can present in atypical ways. Positional maneuvers may help with its timely diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers.

PubMed

Friberg, D; Gazelius, B; Hökfelt, T; Nordlander, B

1997-07-23

Habitual snoring precedes obstructive sleep apnea (OSA), but the pathophysiological mechanisms behind progression are still unclear. The patency of upper airways depends on a reflexogen mechanism reacting on negative intrapharyngeal pressure at inspiration, probably mediated by mucosal receptors, i.e., via afferent nerve endings. Such nerves contain a specific nerve protein, protein-gene product 9.5 (PGP 9.5) and in some cases substance P (SP) and calcitonin gene-related (CGRP). Biopsies of the soft palatial mucosa were obtained from non-smoking men ten OSA patients, 11 habitual snorers and 11 non-snoring controls. The specimens were immunohistochemically analyzed for PGP 9.5, SP and CGRP. As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium. Using double staining methodology, it could be shown that SP- and CGRP-like immunoreactivities (LIs) often coexisted in these fibres, as did CGRP- and PGP 9.5-LIs. The increased density in sensory nerve terminals are interpreted to indicate an afferent nerve lesion. Our results support the hypothesis of a progressive neurogenic lesion as a contributory factor to the collapse of upper airways during sleep in OSA patients.

Mechanical ventilation increases substance P concentration in the vagus, sympathetic, and phrenic nerves.

PubMed

Balzamo, E; Joanny, P; Steinberg, J G; Oliver, C; Jammes, Y

1996-01-01

Substance P (SP), a neurotransmitter localized to primary sensory neurons, is found in the vagus nerve, nodose ganglion, sympathetic chain, and phrenic nerve in various animal species. However, the changes in endogeneous SP concentration under various circumstances that involve the participation of cardiorespiratory afferent nerves are still unexplored. In the present study, attention was focused on the variations in SP content measured by radioimmunoassay (RIA) in respiratory afferent nerves (vagus nerve, cervical sympathetic chain, phrenic nerve) and respiratory muscles (diaphragm, intercostal muscles) during positive inspiratory pressure (PIP) breathing alone or PIP with an expiratory threshold load (ETL) in rabbits. SP was found in all sampled structures in spontaneously breathing control animals, prevailing in the nodose ganglion. Left-versus right-sided differences were noticed in nerves. As compared with that in control animals, the SP concentration was markedly higher in vagal and sympathetic nervous structures during PIP or PIP with ETL, and also in the phrenic nerve during ETL breathing. The SP content did not vary in respiratory muscles. These observations suggest that two very common circumstances of mechanical ventilation are associated with an increased SP concentration in nervous structures participating in the control of breathing.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

NASA Technical Reports Server (NTRS)

Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

Efferent-Mediated Responses in Vestibular Nerve Afferents of the Alert Macaque

PubMed Central

Sadeghi, Soroush G.; Goldberg, Jay M.; Minor, Lloyd B.; Cullen, Kathleen E.

2009-01-01

The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320°/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (∼10 spikes/s) than in regular afferents (∼2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50° upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition. PMID:19091917

Efferent-mediated responses in vestibular nerve afferents of the alert macaque.

PubMed

Sadeghi, Soroush G; Goldberg, Jay M; Minor, Lloyd B; Cullen, Kathleen E

2009-02-01

The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320 degrees/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (approximately 10 spikes/s) than in regular afferents (approximately 2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50 degrees upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition.

Electrophysiological characterization of human rectal afferents

PubMed Central

Ng, Kheng-Seong; Brookes, Simon J.; Montes-Adrian, Noemi A.; Mahns, David A.

2016-01-01

It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and “inflammatory soup” (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3–25) spikes/s vs. 2 (1–4), P < 0.001] and IS [median 5 (range 2–18) spikes/s vs. 2 (1–4), P < 0.001]. Mechanosensitive “hot spots” were identified in 16 nerves [median threshold 2.0 g (range 1.4–6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4–1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. PMID:27789454

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

NASA Technical Reports Server (NTRS)

Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

Reconstruction of the Abdominal Vagus Nerve Using Sural Nerve Grafts in Canine Models

PubMed Central

Luo, Fen; Wang, Zhiming; Wang, Yin

2013-01-01

Background Recently, vagus nerve preservation or reconstruction of vagus has received increasing attention. The present study aimed to investigate the feasibility of reconstructing the severed vagal trunk using an autologous sural nerve graft. Methods Ten adult Beagle dogs were randomly assigned to two groups of five, the nerve grafting group (TG) and the vagal resection group (VG). The gastric secretion and emptying functions in both groups were assessed using Hollander insulin and acetaminophen tests before surgery and three months after surgery. All dogs underwent laparotomy under general anesthesia. In TG group, latency and conduction velocity of the action potential in a vagal trunk were measured, and then nerves of 4 cm long were cut from the abdominal anterior and posterior vagal trunks. Two segments of autologous sural nerve were collected for performing end-to-end anastomoses with the cut ends of vagal trunk (8–0 nylon suture, 3 sutures for each anastomosis). Dogs in VG group only underwent partial resections of the anterior and posterior vagal trunks. Laparotomy was performed in dogs of TG group, and latency and conduction velocity of the action potential in their vagal trunks were measured. The grafted nerve segment was removed, and stained with anti-neurofilament protein and toluidine blue. Results Latency of the action potential in the vagal trunk was longer after surgery than before surgery in TG group, while the conduction velocity was lower after surgery. The gastric secretion and emptying functions were weaker after surgery in dogs of both groups, but in TG group they were significantly better than in VG group. Anti-neurofilament protein staining and toluidine blue staining showed there were nerve fibers crossing the anastomosis of the vagus and sural nerves in dogs of TG group. Conclusion Reconstruction of the vagus nerve using the sural nerve is technically feasible. PMID:23555604

Cross-correlation between vagal afferent impulses from pulmonary mechanoreceptors and high-frequency inflation (HFI) and deflation (HFD) in rabbits.

PubMed

Homma, I; Isobe, A; Iwase, M; Onimaru, H; Sibuya, M

1987-04-10

The effects of high-frequency airway inflation (HFI) and high-frequency airway deflation (HFD) generated by a triangular pressure pulse generator on pulmonary mechanoreceptors were examined. The cross-correlograms between vagal afferent impulses from the slowly adapting (SAR) and the rapidly adapting receptors (RAR) and the HFI or the HFD pulses were analysed. HFI stimulated SAR and RAR and HFD stimulated RAR, but inhibited SAR. The time lag of the mode in the correlogram between SAR and HFI was shorter than that of the mode in the correlogram between RAR and HFI. The span of the mode and the trough of SAR was shorter than the span of the mode of RAR. This may indicate that the time to peak of the generator potential of RAR is longer than that of SAR.

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy.

PubMed

Sadeghi, Soroush G; Minor, Lloyd B; Cullen, Kathleen E

2007-02-01

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1-12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5-15 Hz (20-80 degrees /s) and fast whole-body rotations reaching velocities of 500 degrees /s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of < or =2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs.

PubMed

Coleridge, H M; Coleridge, J C

1977-04-01

We recorded impulses from afferent vagal C-fibres (conduction velocities 0.8-2.4 m/sec) arising from endings in the lungs of anesthetized dogs with open chest. Endings were of two types ('pulmonary' and 'bronchial') distinguished by their response and accessibility to capsaicin and phenyl diguanide injected into the right or left atrium. 'Pulmonary' endings, stimulated only by capsaicin and accessible through the pulmonary circulation, have been described previously. 'Bronchial' endings were stimulated by both capsicin and phenyl diguanide and were accessible through the bronchial circulation. Eight of 28 'bronchial' endings were located in large airways within 4 cm of the hilum, and two were in small airways near the edge of the lung. The precise location of the remaining 'bronchial' endings was not determined but we think that many were in the airways. 'Bronchial' endings had a sparse and irregular spontaneous discharge. They were stimulated by the inhalation of 5% histamine aerosol, the evoked discharge having no obvious relation to the phase of ventilation. A few were weakly stimulated by hyperinflating the lungs; deflation was without effect. The function of these endings is unknown.

Reduced mechanosensitivity of duodenal vagal afferent neurons after an acute switch from milk-based to plant-based diets in anaesthetized pigs.

PubMed

Bligny, D; Blat, S; Chauvin, A; Guérin, S; Malbert, C-H

2005-06-01

Acute changes in diet composition and/or origin alter gastric emptying and gastrointestinal motility. One of the hypotheses explaining these alterations involves changes in the sensitivity of duodenal vagal sensory neurons. The aim of this study was to evaluate the characteristics of multimodal duodenal vagal sensory neurons in 20 pigs feed either with milk-based or plant-based diets of identical caloric content. Twenty duodenal vagal afferents were recorded in anesthetized animal from the cervical vagus using the single fiber method. 10 pigs were fed with a milk-based diet (MD) for one month while the diet of the 10 other pigs was changed for plant-based diet (PD) the day preceding the recording session. The behavior of the receptors was tested in basal resting conditions and after challenges with duodenal intralipid and close intra-arterial injection of CCK, 5-HT or capsaicin with and without isovolumetric duodenal distensions at 20, 40 and 60 mmHg. All receptors were slowly adapting C type fiber with a receptor field located 6-7 cm distal to the pylorus. The rate of discharge during distension (20, 40 and 60 mmHg) combined with duodenal intralipid was significantly larger for MD compared with PD. Similarly, the rate of discharge observed during distensions performed with CCK and with 5-HT were greater for MD compared with PD while CCK and 5-HT without distension were equally stimulating for MD and PD. No significant difference was found between groups during capsaicin infusion irrespective of the stimulating pressure. In conclusion, a switch to plant-based diet, when compared to a milk-based diet, results in an overall decrease in mechanical sensitivity of duodenal neurons during lipid, 5HT and CCK challenges, but not in basal conditions or after capsaicin. This reduced sensitivity to distension may explain the diet-induced alteration of gastric emptying that is controlled primarily through a vago-vagal reflex.

Schwannomatosis of Cervical Vagus Nerve.

PubMed

Abdulla, Faheem Ahmed; Sasi, M P

2016-01-01

Cervical vagal schwannoma is a rare entity among lesions presenting as a neck mass. They are usually slow-growing benign lesions closely associated with the vagus nerve. They are usually solitary and asymptomatic. Multiple schwannomas occurring in patients without neurofibromatosis (NF) are rare and have recently been referred to as schwannomatosis. Here, we present a case of a neck mass that had imaging features suggestive of vagal schwannoma and was operated upon. Intraoperatively, it was discovered to be a case of multiple vagal cervical schwannoma, all directly related to the right vagus nerve, and could be resected from the nerve in toto preserving the function of the vagus nerve. Final HPR confirmed our pre-op suspicion of vagal schwannomatosis.

Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism.

PubMed

Shin, Andrew C; Zheng, Huiyuan; Berthoud, Hans-Rudolf

2012-02-01

To determine the role of the common hepatic branch of the abdominal vagus on the beneficial effects of Roux-en-Y gastric bypass (RYGB) on weight loss, food intake, food choice, and energy expenditure in a rat model. Although changes in gut hormone patterns are the leading candidates in RYGB's effects on appetite, weight loss, and reversal of diabetes, a potential role for afferent signaling through the vagal hepatic branch potentially sensing glucose levels in the hepatic portal vein has recently been suggested in a mouse model of RYGB. Male Sprague-Dawley rats underwent either RYGB alone (RYGB; n = 7), RYGB + common hepatic branch vagotomy (RYGB + HV; n = 6), or sham procedure (sham; n = 9). Body weight, body composition, meal patterns, food choice, energy expenditure, and fecal energy loss were monitored up to 3 months after intervention. Both RYGB and RYGB + HV significantly reduced body weight, adiposity, meal size, and fat preference, and increased satiety, energy expenditure, and respiratory exchange rate compared with sham procedure, and there were no significant differences in these effects between RYGB and RYGB + HV rats. Integrity of vagal nerve supply to the liver, hepatic portal vein, and the proximal duodenum provided by the common hepatic branch is not necessary for RYGB to reduce food intake and body weight or increase energy expenditure. Specifically, it is unlikely that a hepatic portal vein glucose sensor signaling RYGB-induced increased intestinal gluconeogenesis to the brain depends on vagal afferent fibers.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

PubMed

Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

PubMed Central

Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

Schwannomatosis of Cervical Vagus Nerve

PubMed Central

Sasi, M. P.

2016-01-01

Cervical vagal schwannoma is a rare entity among lesions presenting as a neck mass. They are usually slow-growing benign lesions closely associated with the vagus nerve. They are usually solitary and asymptomatic. Multiple schwannomas occurring in patients without neurofibromatosis (NF) are rare and have recently been referred to as schwannomatosis. Here, we present a case of a neck mass that had imaging features suggestive of vagal schwannoma and was operated upon. Intraoperatively, it was discovered to be a case of multiple vagal cervical schwannoma, all directly related to the right vagus nerve, and could be resected from the nerve in toto preserving the function of the vagus nerve. Final HPR confirmed our pre-op suspicion of vagal schwannomatosis. PMID:27807496

TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats

PubMed Central

De Schepper, H U; De Winter, B Y; Van Nassauw, L; Timmermans, J-P; Herman, A G; Pelckmans, P A; De Man, J G

2008-01-01

Patients with inflammatory bowel disease often suffer from gastrointestinal motility and sensitivity disorders. The aim of the current study was to investigate the role of transient receptor potential of the vanilloid type 1 (TRPV1) receptors in the pathophysiology of colitis-induced pelvic afferent nerve sensitization. Trinitrobenzene sulphate (TNBS) colitis (7.5 mg, 30% ethanol) was induced in Wistar rats 72 h prior to the experiment. Single-fibre recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root. Fibres responding to colorectal distension (CRD) were identified in controls and rats with TNBS colitis. The effect of the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-chlorophyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 0.25–5 mg kg−1) or its vehicle (hydroxypropyl-β-cyclodextrin) was tested on the afferent response to repetitive distensions (60 mmHg). Immunocytochemical staining of TRPV1 and NF200, a marker for A-fibre neurons, was performed in the dorsal root ganglia L6–S1. TNBS colitis significantly increased the response to colorectal distension of pelvic afferent C-fibres. BCTC did not significantly affect the C-fibre response in controls, but normalized the sensitized response in rats with colitis. TNBS colitis increased the spontaneous activity of C-fibres, an effect which was insensitive to administration of BCTC. TNBS colitis had no effect on Aδ-fibres, nor was their activity modulated by BCTC. TNBS colitis caused an immunocytochemical up-regulation of TRPV1 receptors in the cell bodies of pelvic afferent NF200 negative neurons. TRPV1 signalling mediates the colitis-induced sensitization of pelvic afferent C-fibres to CRD, while Aδ-fibres are neither sensitized by colitis nor affected by TRPV1 inhibition. PMID:18755744

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

PubMed

Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

2017-09-22

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

PubMed

Hao, Man-Zhao; Xu, Shao-Qin; Hu, Zi-Xiang; Xu, Fu-Liang; Niu, Chuan-Xin M; Xiao, Qin; Lan, Ning

2017-07-14

Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. Our

Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

PubMed Central

Meyers, Kelly; Lim, Audrey; Dye, Matthew; Pak, Diana; Rinaman, Linda; Yates, Bill J.

2014-01-01

Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. PMID:24430885

Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity

PubMed Central

Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

2015-01-01

The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin brainstem slices from rats that were exposed to either a control diet or HFD from pregnancy day 13. Our data demonstrate that following perinatal HFD: (i) DMV neurones had decreased excitability and input resistance with a reduced ability to fire action potentials; (ii) the proportion of DMV neurones excited by cholecystokinin (CCK) was unaltered but the proportion of neurones in which CCK increased excitatory glutamatergic synaptic inputs was reduced; (iii) the tonic activation of presynaptic group II metabotropic glutamate receptors on inhibitory nerve terminals was attenuated, allowing modulation of GABAergic synaptic transmission; and (iv) the size and dendritic arborization of gastric-projecting DMV neurones was increased. These results suggest that perinatal HFD exposure compromises the excitability and responsiveness of gastric-projecting DMV neurones, even in the absence of obesity, suggesting that attenuation of vago-vagal reflex signalling may precede the development of obesity. PMID:25556801

Blood pressure control with selective vagal nerve stimulation and minimal side effects

NASA Astrophysics Data System (ADS)

Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

2014-06-01

Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

PubMed

Rudomin, P; Lomelí, J

2007-01-01

We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

PubMed

Matsukawa, Kanji

2012-01-01

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

PubMed

Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

2018-04-20

Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P < 0.05). Four of seven animals exhibited apneas of ≥20 sec requiring

Vagal activity is quadratically related to prosocial traits, prosocial emotions, and observer perceptions of prosociality.

PubMed

Kogan, Aleksandr; Oveis, Christopher; Carr, Evan W; Gruber, June; Mauss, Iris B; Shallcross, Amanda; Impett, Emily A; van der Lowe, Ilmo; Hui, Bryant; Cheng, Cecilia; Keltner, Dacher

2014-12-01

In the present article, we introduce the quadratic vagal activity-prosociality hypothesis, a theoretical framework for understanding the vagus nerve's involvement in prosociality. We argue that vagus nerve activity supports prosocial behavior by regulating physiological systems that enable emotional expression, empathy for others' mental and emotional states, the regulation of one's own distress, and the experience of positive emotions. However, we contend that extremely high levels of vagal activity can be detrimental to prosociality. We present 3 studies providing support for our model, finding consistent evidence of a quadratic relationship between respiratory sinus arrhythmia--the degree to which the vagus nerve modulates the heart rate--and prosociality. Individual differences in vagal activity were quadratically related to prosocial traits (Study 1), prosocial emotions (Study 2), and outside ratings of prosociality by complete strangers (Study 3). Thus, too much or too little vagal activity appears to be detrimental to prosociality. The present article provides the 1st theoretical and empirical account of the nonlinear relationship between vagal activity and prosociality.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

PubMed

Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

2018-01-01

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication.

PubMed

Gierthmuehlen, Mortimer; Plachta, Dennis T T

2016-02-01

Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. β-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the β1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.

Transcutaneous Vagus Nerve Stimulation: A Promising Method for Treatment of Autism Spectrum Disorders

PubMed Central

Jin, Yu; Kong, Jian

2017-01-01

Transcutaneous Vagus Nerve Stimulation (tVNS) on the auricular branch of the vagus nerve has been receiving attention due to its therapeutic potential for neuropsychiatric disorders. Although the mechanism of tVNS is not yet completely understood, studies have demonstrated the potential role of vagal afferent nerve stimulation in the regulation of mood and visceral state associated with social communication. In addition, a growing body of evidence shows that tVNS can activate the brain regions associated with Autism Spectrum Disorder (ASD), trigger neuroimmune modulation and produce treatment effects for comorbid disorders of ASD such as epilepsy and depression. We thus hypothesize that tVNS may be a promising treatment for ASD, not only for comorbid epilepsy and depression, but also for the core symptoms of ASD. The goal of this manuscript is to summarize the findings and rationales for applying tVNS to treat ASD and propose potential parameters for tVNS treatment of ASD. PMID:28163670

Mechanisms of reflex bladder activation by pudendal afferents

PubMed Central

Woock, John P.; Yoo, Paul B.

2011-01-01

Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by −25% to −39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity.

PubMed

Kopp, Ulla C; Jones, Susan Y; DiBona, Gerald F

2008-12-01

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.

One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

PubMed

Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

2015-09-04

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.

PubMed

Bonvini, Sara J; Birrell, Mark A; Grace, Megan S; Maher, Sarah A; Adcock, John J; Wortley, Michael A; Dubuis, Eric; Ching, Yee-Man; Ford, Anthony P; Shala, Fisnik; Miralpeix, Montserrat; Tarrason, Gema; Smith, Jaclyn A; Belvisi, Maria G

2016-07-01

Sensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored. We hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung. We used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues. Here we show TRPV4-induced activation of guinea pig airway-specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough. This study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP-mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

NASA Technical Reports Server (NTRS)

Rudas, L.; Crossman, A. A.; Morillo, C. A.; Halliwill, J. R.; Tahvanainen, K. U.; Kuusela, T. A.; Eckberg, D. L.

1999-01-01

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

PubMed

Sarr, Michael G; Billington, Charles J; Brancatisano, Roy; Brancatisano, Anthony; Toouli, James; Kow, Lilian; Nguyen, Ninh T; Blackstone, Robin; Maher, James W; Shikora, Scott; Reeds, Dominic N; Eagon, J Christopher; Wolfe, Bruce M; O'Rourke, Robert W; Fujioka, Ken; Takata, Mark; Swain, James M; Morton, John M; Ikramuddin, Sayeed; Schweitzer, Michael; Chand, Bipan; Rosenthal, Raul

2012-11-01

Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15

PubMed Central

Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N.; Langhans, Wolfgang; Lutz, Thomas A.; Blomqvist, Anders

2016-01-01

Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP�

A model-based approach for the evaluation of vagal and sympathetic activities in a newborn lamb.

PubMed

Le Rolle, Virginie; Ojeda, David; Beuchée, Alain; Praud, Jean-Paul; Pladys, Patrick; Hernández, Alfredo I

2013-01-01

This paper proposes a baroreflex model and a recursive identification method to estimate the time-varying vagal and sympathetic contributions to heart rate variability during autonomic maneuvers. The baroreflex model includes baroreceptors, cardiovascular control center, parasympathetic and sympathetic pathways. The gains of the global afferent sympathetic and vagal pathways are identified recursively. The method has been validated on data from newborn lambs, which have been acquired during the application of an autonomic maneuver, without medication and under beta-blockers. Results show a close match between experimental and simulated signals under both conditions. The vagal and sympathetic contributions have been simulated and, as expected, it is possible to observe different baroreflex responses under beta-blockers compared to baseline conditions.

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

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

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

PubMed Central

Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

2016-01-01

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

Distinct Expression of Phenotypic Markers in Placodes- and Neural Crest-Derived Afferent Neurons Innervating the Rat Stomach.

PubMed

Trancikova, Alzbeta; Kovacova, Eva; Ru, Fei; Varga, Kristian; Brozmanova, Mariana; Tatar, Milos; Kollarik, Marian

2018-02-01

Visceral pain is initiated by activation of primary afferent neurons among which the capsaicin-sensitive (TRPV1-positive) neurons play an important role. The stomach is a common source of visceral pain. Similar to other organs, the stomach receives dual spinal and vagal afferent innervation. Developmentally, spinal dorsal root ganglia (DRG) and vagal jugular neurons originate from embryonic neural crest and vagal nodose neurons originate from placodes. In thoracic organs the neural crest- and placodes-derived TRPV1-positive neurons have distinct phenotypes differing in activation profile, neurotrophic regulation and reflex responses. It is unknown to whether such distinction exists in the stomach. We hypothesized that gastric neural crest- and placodes-derived TRPV1-positive neurons express phenotypic markers indicative of placodes and neural crest phenotypes. Gastric DRG and vagal neurons were retrogradely traced by DiI injected into the rat stomach wall. Single-cell RT-PCR was performed on traced gastric neurons. Retrograde tracing demonstrated that vagal gastric neurons locate exclusively into the nodose portion of the rat jugular/petrosal/nodose complex. Gastric DRG TRPV1-positive neurons preferentially expressed markers PPT-A, TrkA and GFRα 3 typical for neural crest-derived TRPV1-positive visceral neurons. In contrast, gastric nodose TRPV1-positive neurons preferentially expressed markers P2X 2 and TrkB typical for placodes-derived TRPV1-positive visceral neurons. Differential expression of neural crest and placodes markers was less pronounced in TRPV1-negative DRG and nodose populations. There are phenotypic distinctions between the neural crest-derived DRG and placodes-derived vagal nodose TRPV1-positive neurons innervating the rat stomach that are similar to those described in thoracic organs.

Plasticity of vagal brainstem circuits in the control of gastric function

PubMed Central

Browning, Kirsteen N.; Travagli, R. Alberto

2010-01-01

Background Sensory information from the viscera, including the gastrointestinal (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory information to regulate autonomic functions and homeostasis. The integrated response is conveyed to, amongst other nuclei, the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and catecholamines as neurotransmitters. Despite being modulated by almost all the neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV does not appear to be tonically active in the control of gastric motility and tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to the DMV appears critical in setting gastric tone and motility, yet, under basal conditions, this synapse appears resistant to modulation. Purpose Here, we review the available evidence suggesting that vagal efferent output to the GI tract is regulated, perhaps even controlled, in an “on-demand” and efficient manner in response to ever-changing homeostatic conditions. The focus of this review is on the plasticity induced by variations in the levels of second messengers in the brainstem neurons that form vago-vagal reflex circuits. Emphasis is placed upon the modulation of GABAergic transmission to DMV neurons and the modulation of afferent input from the GI tract by neurohormones/neurotransmitters and macronutrients. Derangement of this “on-demand” organization of brainstem vagal circuits may be one of the factors underlying the pathophysiological changes observed in functional dyspepsia or hyperglycemic gastroparesis. PMID:20804520

Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.

PubMed

Sandler, A D; Schlegel, J F; DeSautel, M G; Maher, J W

1993-10-01

Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.

Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

PubMed Central

Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

2004-01-01

We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

Inhibitory neurotransmission regulates vagal efferent activity and gastric motility

PubMed Central

McMenamin, Caitlin A; Travagli, R Alberto

2016-01-01

The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions. PMID:27302177

Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

PubMed

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E

1978-01-01

The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

PubMed Central

Kopp, Ulla C.; Jones, Susan Y.; DiBona, Gerald F.

2008-01-01

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, −60 ± 4 vs. −77 ± 6%. Maximum gain, −4.22 ± 0.45 vs. −6.04 ± 0.90% ΔERSNA/mmHg, and the maximum value of instantaneous gain, −4.19 ± 0.45 vs. −6.04 ± 0.81% ΔERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 ± 0.2 vs. 6.1 ± 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 ± 4,900 vs. 20,900 ± 3,410%·s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet. PMID:18945951

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

PubMed

Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

2013-09-01

limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

PubMed

Morimoto, H; Matsuda, A; Ohori, M; Fujii, T

1996-06-01

We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15.

PubMed

Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N; Langhans, Wolfgang; Lutz, Thomas A; Blomqvist, Anders; Riediger, Thomas

2017-06-01

The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice. Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action. © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle

Effects from fine muscle and cutaneous afferents on spinal locomotion in cats

PubMed Central

Kniffki, K.-D.; Schomburg, E. D.; Steffens, H.

1981-01-01

1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l-DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi- and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar α-motoneurones. 2. After nialamide but before treatment with l-DOPA, in some cases, transient locomotor-like discharges were induced by an increased activity in fine muscle afferents. The response pattern in nerves to both hind limbs could be different showing e.g. only transient alternating activity between knee flexor and extensor of one limb but not of the other one. 3. Treatment with l-DOPA did not always cause fictive locomotion. Often not all motoneurone pools showed rhythmic activity. In these cases stimulation of group III and IV muscle afferents usually caused transient periodic activity. In cases with apparent rhythmic activity, algesic stimulation of the gastrocnemius—soleus muscle caused an accentuation of the rhythm by a more abrupt transition from the active phase to the non-active interval. Again, the response patterns on both sides were not uniform in all cases. 4. A second type of response to activation of fine muscle afferents had a quite different character: the rhythmic activity was more or less completely overridden by a strong transient tonic hyperactivity or the rhythm was transiently blocked. These phenomena did not occur in the same way in all nerves. 5. Electrical stimulation of cutaneous nerves of the hind limb generally induced the same response pattern as chemical stimulation of the group III and IV muscle afferents. The effects varied depending on the stimulus strength and the nerve. 6. The results revealed that cutaneous and fine muscle afferents not only

Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus

PubMed Central

Izumi, Noriaki; Matsuyama, Hayato; Ko, Mifa; Shimizu, Yasutake; Takewaki, Tadashi

2003-01-01

Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 μs, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones. PMID:12813149

Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa.

PubMed

Pabst, M A; Schöninkle, E; Holzer, P

1993-07-01

Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa.

Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium

PubMed Central

Hoover, Donald B.; Shepherd, Angela V.; Southerland, E. Marie; Armour, J. Andrew; Ardell, Jeffrey L.

2008-01-01

While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T3 DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T3 DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30–40% of ventricular afferent somata in T3 DRG). About 30% of the ventricular afferent neurons in T2 DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB4. Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters. PMID:18558516

Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium.

PubMed

Hoover, Donald B; Shepherd, Angela V; Southerland, E Marie; Armour, J Andrew; Ardell, Jeffrey L

2008-08-18

While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T(3) DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T(3) DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30-40% of ventricular afferent somata in T(3) DRG). About 30% of the ventricular afferent neurons in T(2) DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB(4). Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters.

Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

PubMed

Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

2015-01-01

Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

PubMed

Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

2003-06-01

Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

Vagal Nerve Stimulation Evoked Heart Rate Changes and Protection from Cardiac Remodeling.

PubMed

Agarwal, Rahul; Mokelke, Eric; Ruble, Stephen B; Stolen, Craig M

2016-02-01

This study investigated whether vagal nerve stimulation (VNS) leads to improvements in ischemic heart failure via heart rate modulation. At 7 ± 1 days post left anterior descending artery (LAD) ligation, 63 rats with myocardial infarctions (MI) were implanted with ECG transmitters and VNS devices (MI + VNS, N = 44) or just ECG transmitters (MI, N = 17). VNS stimulation was active from 14 ± 1 days to 8 ± 1 weeks post MI. The average left ventricular (LV) end diastolic volumes at 8 ± 1 weeks were MI = 672.40 μl and MI + VNS = 519.35 μl, p = 0.03. The average heart weights, normalized to body weight (± std) at 14 ± 1 weeks were MI = 3.2 ± 0.6 g*kg(-1) and MI + VNS = 2.9 ± 0.3 g*kg(-1), p = 0.03. The degree of cardiac remodeling was correlated with the magnitude of acute VNS-evoked heart rate (HR) changes. Further research is required to determine if the acute heart rate response to VNS activation is useful as a heart failure biomarker or as a tool for VNS therapy characterization.

Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses

PubMed Central

Ikeda, Ryo; Cha, Myeounghoon; Ling, Jennifer; Jia, Zhanfeng; Coyle, Dennis; Gu, Jianguo G.

2014-01-01

SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions. PMID:24746027

[Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

PubMed

Xue, Run-Qing; Xu, Man; Yu, Xiao-Jiang; Liu, Long-Zhu; Zang, Wei-Jin

2017-10-25

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters.

PubMed

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E

2009-09-20

The sense of taste is crucial in an animal's determination as to what is edible and what is not. This gustatory function is especially important in goldfish, who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe, which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons that have radially directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca(++)-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3-hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediate neurotransmission between reflex interneurons and vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system.

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish Cellular organization and neurotransmitters

PubMed Central

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E.

2009-01-01

The sense of taste is crucial in an animal’s determination as to what is edible and what is not. This gustatory function is especially important in goldfish who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons which have radially-directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca++-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (±)-α-amino-3-hydroxy-5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediates neurotransmission between reflex interneurons and vagal motoneurons. Thus the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system. PMID:19598285

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

PubMed

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

Transfer characteristics of the hair cell's afferent synapse

NASA Astrophysics Data System (ADS)

Keen, Erica C.; Hudspeth, A. J.

2006-04-01

The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

PubMed

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

Local opiate receptors in the sinoatrial node moderate vagal bradycardia.

PubMed

Farias, M; Jackson, K; Stanfill, A; Caffrey, J L

2001-02-20

Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused into the systemic circulation. This study was designed to locate the opiate receptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardiac parasympathetic ganglia or the pre-junctional nerve terminals innervating the sinoatrial node. In this study 10 dogs were instrumented with a microdialysis probe inserted into the sinoatrial node. The functional position of the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimulations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorded on-line. MEAP was infused directly into the sinoatrial node via the microdialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenorphine co-infused with MEAP. MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultaneous local nodal blockade of these receptors with the opiate antagonist, diprenorphine, eliminated the effect of MEAP demonstrating the participation by opiate receptors. Systemic infusions of MEAP produced a reduction in vagal bradycardia nearly identical to that observed during nodal administration. When local nodal opiate receptors were blocked with diprenorphine, the systemic effect of MEAP was eliminated. These data lead us to suggest that the opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-nodal or ganglionic receptors.

Vagal innervation of the aldosterone-sensitive HSD2 neurons in the NTS

PubMed Central

Shin, Jung-Won; Geerling, Joel C.; Loewy, Arthur D.

2009-01-01

The nucleus of the solitary tract (NTS) contains a unique subpopulation of aldosterone-sensitive neurons. These neurons express the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) and are activated by sodium deprivation. They are located in the caudal NTS, a region which is densely innervated by the vagus nerve, suggesting that they could receive direct viscerosensory input from the periphery. To test this possibility, we injected the highly sensitive axonal tracer biotinylated dextran amine (BDA) into the left nodose ganglion in rats. Using confocal microscopy, we observed a sparse input from the vagus to most HSD2 neurons. Roughly 80% of the ipsilateral HSD2 neurons exhibited at least one close contact with a BDA-labeled vagal bouton, although most of these cells received only a few total contacts. Most of these contacts were axo-dendritic (~80%), while ~20% were axo-somatic. In contrast, the synaptic vesicular transporters VGLUT2 or GAD7 labeled much larger populations of boutons contacting HSD2-labeled dendrites and somata, suggesting that direct input from the vagus may only account for a minority of the information integrated by these neurons. In summary, the aldosterone-sensitive HSD2 neurons in the NTS appear to receive a small amount of direct viscerosensory input from the vagus nerve. The peripheral sites of origin and functional significance of this projection remain unknown. Combined with previously-identified central sources of input to these cells, the present finding indicates that the HSD2 neurons integrate humoral information with input from a variety of neural afferents. PMID:19010311

The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

PubMed

van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

2016-03-01

Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

Central projections and entries of capsaicin-sensitive muscle afferents.

PubMed

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity.

PubMed

Campaniello, M A; Harrington, A M; Martin, C M; Ashley Blackshaw, L; Brierley, S M; Hughes, P A

2016-01-01

Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown. Myeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and NaV 1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice. MPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p < 0.05), and the abundance of IL-2R and NaV 1.7 mRNA was increased 3.5- and 2-fold (p < 0.001 for both) in colo-rectal DRG neurons. IL-2, an immune mediator from the adaptive arm of the immune response, affects colo-rectal afferent function, indicating these effects are not restricted to innate immune mediators. Colo-rectal afferent sensitivity to IL-2 is increased long after healing from inflammation. © 2015 John Wiley & Sons Ltd.

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

PubMed

Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

2017-05-01

/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

PubMed

Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

2014-01-01

Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

The modulation of visceral functions by somatic afferent activity.

PubMed

Sato, A; Schmidt, R F

1987-01-01

We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice.

PubMed

Fox, E A; Biddinger, J E; Jones, K R; McAdams, J; Worman, A

2013-01-15

Global-heterozygous and brain-specific homozygous knockouts (KOs) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from the gut to the brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus nerve (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

The serotonin receptor mediates changes in autonomic neurotransmission and gastrointestinal transit induced by heat-killed Lactobacillus brevis SBC8803.

PubMed

Horii, Y; Nakakita, Y; Misonou, Y; Nakamura, T; Nagai, K

2015-01-01

Lactobacilli exhibit several health benefits in mammals, including humans. Our previous reports established that heat-killed Lactobacillus brevis SBC8803 (SBC8803) increased both efferent gastric vagal nerve activity and afferent intestinal vagal nerve activity in rats. We speculated that this strain could be useful for the treatment of gastrointestinal (GI) disorders. In this study, we examined the effects of SBC8803 on peristalsis and the activity of the efferent celiac vagal nerve innervating the intestine in rats. First, we examined the effects of intraduodenal (ID) administration of SBC8803 on efferent celiac vagal nerve activity (efferent CVNA) in urethane-anesthetised rats using electrophysiological studies. The effects of intravenous injection of the serotonin 5-HT3 receptor antagonist granisetron on changes in efferent CVNA due to ID administration of SBC8803 were also investigated. Finally, the effects of oral gavage of SBC8803 on GI transit were analysed using the charcoal propulsion method in conscious rats treated with or without granisetron. ID administration of SBC8803 increased efferent CVNA. Pretreatment with granisetron eliminated SBC8803-dependent changes in efferent CVNA. Furthermore, oral gavage of SBC8803 significantly accelerated GI transit, while pretreatment with granisetron inhibited GI transit. Our findings suggested that SBC8803 increased efferent CVNA and GI transit of charcoal meal via 5-HT3 receptors. Moreover, SBC8803 enhanced the activity of efferent vagal nerve innervating the intestine and promoted peristalsis via 5-HT3 receptors.

Sensory neurons that detect stretch and nutrients in the digestive system

PubMed Central

Williams, Erika K.; Chang, Rui B.; Strochlic, David E.; Umans, Benjamin D.; Lowell, Bradford B.; Liberles, Stephen D.

2016-01-01

SUMMARY Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology. PMID:27238020

Role of renal sensory nerves in physiological and pathophysiological conditions

PubMed Central

2014-01-01

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

PubMed Central

Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

2014-01-01

Crohn’s disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8∶00 AM and 10∶00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = −0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = −0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases. PMID

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

2001-01-01

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

NASA Technical Reports Server (NTRS)

Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

1998-01-01

There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

Radiofrequency Catheter Ablation for Atrial Fibrillation Elicited "Jackhammer Esophagus": A New Complication Due to Vagal Nerve Stimulation?

PubMed

Tolone, Salvatore; Savarino, Edoardo; Docimo, Ludovico

2015-10-01

Radiofrequency catheter ablation (RFCA) is a potentially curative method for treatment of highly symptomatic and drug-refractory atrial fibrillation (AF). However, this technique can provoke esophageal and nerve lesion, due to thermal injury. To our knowledge, there have been no reported cases of a newly described motor disorder, the Jackhammer esophagus (JE) after RFCA, independently of GERD. We report a case of JE diagnosed by high-resolution manometry (HRM), in whom esophageal symptoms developed 2 weeks after RFCA, in absence of objective evidence of GERD. A 65-year-old male with highly symptomatic, drug-refractory paroxysmal AF was candidate to complete electrical pulmonary vein isolation with RFCA. Prior the procedure, the patient underwent HRM and impedance-pH to rule out GERD or hiatal hernia presence. All HRM parameters, according to Chicago classification, were within normal limits. No significant gastroesophageal reflux was documented at impedance pH monitoring. Patient underwent RFCA with electrical disconnection of pulmonary vein. After two weeks, patient started to complain of dysphagia for solids, with acute chest-pain. The patient repeated HRM and impedance-pH monitoring 8 weeks after RFCA. HRM showed in all liquid swallows the typical spastic hypercontractile contractions consistent with the diagnosis of JE, whereas impedance-pH monitoring resulted again negative for GERD. Esophageal dysmotility can represent a possible complication of RFCA for AF, probably due to a vagal nerve injury, and dysphagia appearance after this procedure must be timely investigated by HRM.

Neuroanatomical basis of Sandifer's syndrome: a new vagal reflex?

PubMed

Cerimagic, Denis; Ivkic, Goran; Bilic, Ervina

2008-01-01

Sandifer's syndrome is a gastrointestinal disorder with neurological features. It is characterized by reflex torticollis following deglutition in patients with gastroesophageal reflux and/or hiatal hernia. The authors believe that neurological manifestations of the syndrome are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii (NTS). Three models for the neuroanatomical basis of the hypothetic reflex arc are presented. In the first one the hypothetic reflex arc is based on the classic hypothesis of two components nervus accessorius (n.XI) - radix cranialis (RC) and radix spinalis (RS) The nervous impulses are transmitted by nervus vagus (n.X) general visceral afferent (GVA) fibers to NTS situated in medulla oblongata, then by interneuronal connections on nucleus ambiguus (NA) and nucleus dorsalis nervi vagi (NDX). Special visceral efferent fibers (SVE) impulses from NA are in part transferred to n.XI ramus externus (RE) (carrying the majority of general somatic efferent (GSE) fibers) via hypothetic anastomoses in the region of foramen jugulare. This leads to contraction of trapezius and sternocleidomastoideus muscles, and the occurrence of intermittent torticollis. In the second suggested neuroanatomical model the hypothetic reflex arc is organized in the absence of n.XI RC, the efferent part of the reflex arc continues as NA, which is motor nucleus of nervus glossopharyngeus (n.IX) and n.X in this case while distal roots of n.XI that appear at the level of the olivary nucleus lower edge represent n.X roots. In the third presented model the hypothetic reflex arc includes no jugular transfer and could be realized via interneuronal connections directly from NTS to the spinal motoneurons within nucleus radicis spinalis nervi accessorii (NRS n.XI) or from NA to NRS n.XI. The afferent segment of the postulated reflex arc in all three models is mediated via n.X. We conclude that Sandifer's syndrome is a clinical manifestation of another

Chicken (Gallus domesticus) inner ear afferents

NASA Technical Reports Server (NTRS)

Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.

1998-01-01

Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis.

PubMed

Jin, Haifeng; Guo, Jie; Liu, Jiemin; Lyu, Bin; Foreman, Robert D; Yin, Jieyun; Shi, Zhaohong; Chen, Jiande D Z

2017-09-01

The purpose of this study was to determine the effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-trinitrobenzenesulfonic acid). The rats were then treated with sham ES (electrical stimulation), VNS, or VNS + EA for 3 wk. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, plasma levels of TNFα, IL-1β, and IL-6, and myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. It was found that 1 ) the area under curve (AUC) of DAI was substantially decreased with VNS + EA and VNS, with VNS + EA being more effective than VNS ( P < 0.001); 2 ) the macroscopic score was 6.43 ± 0.61 in the sham ES group and reduced to 1.86 ± 0.26 with VNS ( P < 0.001) and 1.29 ± 0.18 with VNS + EA ( P < 0.001); 3 ) the histological score was 4.05 ± 0.58 in the sham ES group and reduced to 1.93 ± 0.37 with VNS ( P < 0.001) and 1.36 ± 0.20 with VNS + EA ( P < 0.001); 4 ) the plasma levels of TNFα, IL-1β, IL-6, and MPO were all significantly decreased with VNS and VNS + EA compared with the sham ES group; and 5 ) autonomically, both VNS + EA and VNS substantially increased vagal activity and decreased sympathetic activity compared with sham EA ( P < 0.001, P < 0.001, respectively). In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS. NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid

Effect of vagal stimulation on gastric mucosal barrier in albino rats.

PubMed

Somasundaram, K; Ganguly, A K

1987-01-01

To study the influence of vagus nerves on gastric mucosal barrier in albino rats, gastric adherent mucus and mucosal epithelial neutral glycoproteins were quantitatively assessed after vagal stimulation at the cardio-esophageal region by a specially designed circular electrode. Gastric adherent mucus and epithelial mucus were studied from oxyntic and pyloric gland areas by Alcian blue binding and periodic acid Schiff's (PAS) staining method respectively. The results when compared with sham operated control animals showed increase in the visible mucus concurrent with decrease in PAS positive materials. The stimulation at the cardio-esophageal region of vagotomized animals did not produce these effects. This study indicates that in an acute condition, increased vagal influence is important in increasing mucus secretion and strengthening the first line of defence of the mucosal barrier.

Differential central projections of vestibular afferents in pigeons

NASA Technical Reports Server (NTRS)

Dickman, J. D.; Fang, Q.

1996-01-01

The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

NASA Technical Reports Server (NTRS)

Cox, James F.; Tahvanainen, Kari U O.; Kuusela, Tom A.; Levine, Benjamin D.; Cooke, William H.; Mano, Tadaaki; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Ertl, Andrew C.;

Resection of cervical vagal schwannoma via a post-auricular approach.

PubMed

Roh, Jong-Lyel

2006-03-01

Cervical vagal schwannomas are extremely rare and gross total resection is the standard treatment modality. However, because the conventional cervical approach leaves an incision scar in a visible area, other approaches need to be developed for young women who want the postoperative scar to be invisible. A 28-year-old female underwent complete resection of a 4x4 cm tumor in her right upper neck via a post-auricular approach using an inverted V-shaped incision along the post-auricular sulcus and hairline. The tumor was a schwannoma originating from the right cervical vagus nerve. Postoperatively, right vocal cord paralysis developed despite careful dissection but completely recovered within 6 months after surgery. The patient was satisfied with an invisible external scar which was hidden by her auricle and hair. A cervical vagal schwannoma can be successfully removed by making an incision in a potentially invisible area.

Pulmonary vein region ablation in experimental vagal atrial fibrillation: role of pulmonary veins versus autonomic ganglia.

PubMed

Lemola, Kristina; Chartier, Denis; Yeh, Yung-Hsin; Dubuc, Marc; Cartier, Raymond; Armour, Andrew; Ting, Michael; Sakabe, Masao; Shiroshita-Takeshita, Akiko; Comtois, Philippe; Nattel, Stanley

2008-01-29

Pulmonary vein (PV) -encircling radiofrequency ablation frequently is effective in vagal atrial fibrillation (AF), and there is evidence that PVs may be particularly prone to cholinergically induced arrhythmia mechanisms. However, PV ablation procedures also can affect intracardiac autonomic ganglia. The present study examined the relative role of PVs versus peri-PV autonomic ganglia in an experimental vagal AF model. Cholinergic AF was studied under carbachol infusion in coronary perfused canine left atrial PV preparations in vitro and with cervical vagal stimulation in vivo. Carbachol caused dose-dependent AF promotion in vitro, which was not affected by excision of all PVs. Sustained AF could be induced easily in all dogs during vagal nerve stimulation in vivo both before and after isolation of all PVs with encircling lesions created by a bipolar radiofrequency ablation clamp device. PV elimination had no effect on atrial effective refractory period or its responses to cholinergic stimulation. Autonomic ganglia were identified by bradycardic and/or tachycardic responses to high-frequency subthreshold local stimulation. Ablation of the autonomic ganglia overlying all PV ostia suppressed the effective refractory period-abbreviating and AF-promoting effects of cervical vagal stimulation, whereas ablation of only left- or right-sided PV ostial ganglia failed to suppress AF. Dominant-frequency analysis suggested that the success of ablation in suppressing vagal AF depended on the elimination of high-frequency driver regions. Intact PVs are not needed for maintenance of experimental cholinergic AF. Ablation of the autonomic ganglia at the base of the PVs suppresses vagal responses and may contribute to the effectiveness of PV-directed ablation procedures in vagal AF.

Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia.

PubMed

García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; Eleno, Nélida; Morán, Asunción

2017-01-01

5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor.

TRP channel functions in the gastrointestinal tract.

PubMed

Yu, Xiaoyun; Yu, Mingran; Liu, Yingzhe; Yu, Shaoyong

2016-05-01

Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

PubMed

Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

2016-05-02

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

Neuropeotide Y changes the excitability of fine afferent units in the rat knee joint

PubMed Central

Just, Stefan; Heppelmann, Bernd

2001-01-01

The aim of the present study was to examine the effects of the sympathetic co-transmitter Neuropeotide Y on primary afferent nerve fibres of the rat knee joint. The responses to passive joint rotations at defined torque were recorded from 41 slowly conducting afferent nerve fibres (0.9 – 18.8 m s−1) innervating the knee joint capsule. About 70% of the joint afferents were significantly affected in their mechanosensitivity by topical application of Neuropeptide Y. Significant effects occurred at a concentration of 10 nM. Decreased mechanosensitivity was observed in about 40% of nerve fibres, whereas 30% of the units increased the mechanosensitivity. In addition, in about 35% of the fibres resting activity was induced or increased. Neither the conduction velocity nor the mechanical threshold of the units correlated with the described effects of Neuropeptide Y. NPY(13 – 36), a specific Y2-receptor agonist, only modulated the mechanosensitivity, with no effect on the resting activity. The effects on the mechanosensitivity were similar to Neuropeptide Y, i.e. increase and decrease of the response. Studies with the Y1-agonist (Leu31, Pro34)-NPY showed that activation of the Y1-receptor predominantly resulted in an enhanced mechanosensitivity and an induction or increase of a resting activity. The opposite effect was observed by application of BIBP 3226 BS, a Y1-receptor antagonist. In conclusion, these data indicate that Neuropeptide Y affects the excitability of sensory nerve fibre endings. PMID:11159723

Effects of tachykinin receptor agonists and antagonists on the guinea-pig isolated oesophagus.

PubMed

Kerr, K P

2000-11-01

1. Vagal nerve stimulation of the guinea-pig isolated oesophagus produced a triphasic tetrodotoxin (TTX)-sensitive contractile response. The third phase, which was resistant to ganglion blocking drugs, was selectively abolished by capsaicin, suggesting the involvement of one or more neuropeptides released from afferent neurons. Receptors on cholinergic neurons were subsequently activated because the response was atropine sensitive. Contractile responses resulting from exogenous substance P were abolished by atropine and TTX and enhanced by physostigmine. These findings suggest that the third phase may be mediated by the action of a substance P-like neuropeptide released from sensory nerve endings that subsequently activated cholinergic neurons. 2. The tachykinin receptors in the body of the guinea-pig oesophagus were characterized by determining the relative agonist potencies of natural tachykinins as well as tachykinin receptor-selective analogues. Antagonist affinities were also determined. The results indicated the presence of both NK2 and NK3 receptors. In addition, the effects of a cocktail of peptidase inhibitors (captopril, thiorphan and amastatin) on responses to various tachykinins and synthetic analogues were determined. The results indicate that one or more peptidases are present in this preparation. 3. Experiments using various tachykinin receptor antagonists were performed to determine whether the activation of tachykinin receptors played a role in the mediation of the third phase of the response to vagal nerve stimulation. While this response was unaffected by NK1 and NK2 receptor-selective antagonists, it was only partially inhibited (23%) by the NK3 receptor antagonist SR 142801. Thus, in the guinea-pig oesophagus, it appears that NK3 receptors play only a minor role in mediating a contractile response when afferent neurons are excited by vagal nerve stimulation.

The modulatory effects of noradrenaline on vagal control of heart rate in the dogfish, Squalus acanthias.

PubMed

Agnisola, Claudio; Randall, David J; Taylor, Edwin W

2003-01-01

The possible interactions between inhibitory vagal control of the heart and circulating levels of catecholamines in dogfish (Squalus acanthias) were studied using an in situ preparation of the heart, which retained intact its innervation from centrally cut vagus nerves. The response to peripheral vagal stimulation typically consisted of an initial cardiac arrest, followed by an escape beat, leading to renewed beating at a mean heart rate lower than the prestimulation rate (partial recovery). Cessation of vagal stimulation led to a transient increase in heart rate, above the prestimulation rate. This whole response was completely abolished by 10(-4) M atropine (a muscarinic cholinergic antagonist). The degree of vagal inhibition was evaluated in terms of both the initial, maximal cardiac interval and the mean heart rate during partial recovery, both expressed as a percentage of the prestimulation heart rate. The mean prestimulation heart rate of this preparation (36+/-4 beats min(-1)) was not affected by noradrenaline but was significantly reduced by 10(-4) M nadolol (a beta-adrenergic receptor antagonist), suggesting the existence of a resting adrenergic tone arising from endogenous catecholamines. The degree of vagal inhibition of heart rate varied with the rate of stimulation and was increased by the presence of 10(-8) M noradrenaline (the normal in vivo level in routinely active fish), while 10(-7) M noradrenaline (the in vivo level measured in disturbed or deeply hypoxic fish) reduced the cardiac response to vagal stimulation. In the presence of 10(-7) M noradrenaline, 10(-4) M nadolol further reduced the vagal response, while 10(-4) M nadolol + 10(-4) M phentolamine had no effect, indicating a complex interaction between adrenoreceptors, possibly involving presynaptic modulation of vagal inhibition.

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

The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective.

PubMed

Al Omari, Ahmad I; Alzoubi, Firas Q; Alsalem, Mohammad M; Aburahma, Samah K; Mardini, Diala T; Castellanos, Paul F

Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years. VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively. This study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion. Series of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation. Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation. Seizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70-90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency. The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems. Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a

Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves.

PubMed

Holzer-Petsche, U

1991-08-01

1. Extrinsic reflexes elicited by changes in gastric wall tension play an important role in regulating gastric tone. The present study investigated whether such reflexes modulate gastric contractions induced by close arterially administered neurokinin A (NKA), substance P (SP), SP-methylester and bethancehol in anaesthetized rats. 2. Reflex pathways were acutely interrupted by either subdiaphragmatic vagotomy or prevertebral ganglionectomy. C-fibre afferent nerve activity was abolished by pretreating rats with capsaicin 10 to 16 days before the experiments. 3. The order of potency in inducing gastric contractions was NKA greater than SP greater than bethanechol. SP-methylester was markedly less effective than SP and its effects did not fit sigmoid dose-response curves (DRCs). The maximal responses to NKA, SP, and bethanechol were similar, whilst the DRC for SP was significantly flatter than those for NKA or bethanechol. Pretreatment of the rats with the peptidase inhibitors phosphoramidon or captopril did not increase the contractile response to SP. 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left. 5. Capsaicin pretreatment did not change the DRC for NKA in rats with intact vagus but shifted that for bethanechol to the left. The leftward of the DRC for NKA caused by vagotomy was prevented in capsaicin-pretreated rats whereas the vagotomy-induced shift of the DRC for bethanechol remained unaltered. The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment. 6. These data may be interpreted as demonstrating two neuronal mechanisms for modulating drug-induced gastric contractions. First, the contractions themselves activate a vago-vagal negative feedback involving capsaicin-sensitive afferents. Second, NKA, and to a lesser degree SP, seem to induce a nonvagal non-splanchnic mechanism which via capsaicin

Anatomy and physiology of the afferent visual system.

PubMed

Prasad, Sashank; Galetta, Steven L

2011-01-01

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. 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.

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

Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder.

PubMed

Downie, J W; Armour, J A

1992-11-01

The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure.

Vagal Flexibility: A Physiological Predictor of Social Sensitivity

PubMed Central

Muhtadie, Luma; Akinola, Modupe; Koslov, Katrina; Mendes, Wendy Berry

2015-01-01

This research explores vagal flexibility— dynamic modulation of cardiac vagal control—as an individual-level physiological index of social sensitivity. In 4 studies, we test the hypothesis that individuals with greater cardiac vagal flexibility, operationalized as higher cardiac vagal tone at rest and greater cardiac vagal withdrawal (indexed by a decrease in respiratory sinus arrhythmia) during cognitive or attentional demand, perceive social-emotional information more accurately and show greater sensitivity to their social context. Study 1 sets the foundation for this investigation by establishing that vagal flexibility can be elicited consistently in the laboratory and reliably over time. Study 2 demonstrates that vagal flexibility has different associations with psychological characteristics than does vagal tone, and that these characteristics are primarily social in nature. Study 3 links individual differences in vagal flexibility with accurate detection of social and emotional cues depicted in still facial images. Study 4 demonstrates that individuals with greater vagal flexibility respond to dynamic social feedback in a more context-sensitive manner than do individuals with less vagal flexibility. Specifically, compared with their less flexible counterparts, individuals with greater vagal flexibility, when assigned to receive negative social feedback, report more shame, show more pronounced blood pressure responses, and display less sociable behavior, but when receiving positive social feedback display more sociable behavior. Taken together, these findings suggest that vagal flexibility is a useful individual difference physiological predictor of social sensitivity, which may have implications for clinical, developmental, and health psychologists. PMID:25545841

Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

PubMed

Liddy, Whitney; Barber, Samuel R; Lin, Brian M; Kamani, Dipti; Kyriazidis, Natalia; Lawson, Bradley; Randolph, Gregory W

2018-01-01

Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. Retrospective review. Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. 4. Laryngoscope, 128:283-289, 2018. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea.

PubMed

Drescher, M J; Drescher, D G; Khan, K M; Hatfield, J S; Ramakrishnan, N A; Abu-Hamdan, M D; Lemonnier, L A

2006-09-29

Pituitary adenylyl cyclase-activating polypeptide (PACAP), via its specific receptor pituitary adenylyl cyclase-activating polypeptide receptor 1 (PAC1-R), is known to have roles in neuromodulation and neuroprotection associated with glutamatergic and cholinergic neurotransmission, which, respectively, are believed to form the primary basis for afferent and efferent signaling in the organ of Corti. Previously, we identified transcripts for PACAP preprotein and multiple splice variants of its receptor, PAC1-R, in microdissected cochlear subfractions. In the present work, neural localizations of PACAP and PAC1-R within the organ of Corti and spiral ganglion were examined, defining sites of PACAP action. Immunolocalization of PACAP and PAC1-R in the organ of Corti and spiral ganglion was compared with immunolocalization of choline acetyltransferase (ChAT) and synaptophysin as efferent neuronal markers, and glutamate receptor 2/3 (GluR2/3) and neurofilament 200 as afferent neuronal markers, for each of the three cochlear turns. Brightfield microscopy giving morphological detail for individual immunolocalizations was followed by immunofluorescence detection of co-localizations. PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti. Further, evidence was obtained that PACAP is expressed in type I afferent axons leaving the spiral ganglion en route to the auditory nerve, potentially serving as a neuromodulator in axonal terminals. In contrast to the efferent localization of PACAP within the organ of Corti, PAC1-R immunoreactivity was co-localized with afferent dendritic neuronal marker GluR2/3 in nerve fibers passing beneath and lateral to the inner hair cell and in fibers at supranuclear and basal sites on outer hair cells. Given the known association of PACAP with catecholaminergic neurotransmission in sympathoadrenal function, we also re-examined the issue

St. John’s Wort enhances the synaptic activity of the nucleus of the solitary tract

PubMed Central

Vance, Katie M.; Ribnicky, David M.; Hermann, Gerlinda E.; Rogers, Richard C.

2014-01-01

Objective St. John’s Wort extract, which is commonly used to treat depression, inhibits the reuptake of several neurotransmitters, including glutamate, serotonin, norepinephrine, and dopamine. Glutamatergic visceral vagal afferents synapse upon neurons of the solitary tract (NST); thus, we evaluated whether St. John’s Wort extract modulates glutamatergic neurotransmission within the NST. Materials and Methods We used live cell calcium imaging to evaluate whether St. John’s Wort and its isolated components hypericin and hyperforin increase the excitability of pre-labeled vagal afferent terminals synapsing upon the NST. We used voltage-clamp recordings of spontaneous miniature excitatory postsynaptic currents (mEPSCs) to evaluate whether St. John’s Wort alters glutamate release from vagal afferents onto NST neurons. Results Our imaging data show that St. John’s Wort (50 μg/mL) increased the intracellular calcium levels of stimulated vagal afferent terminals compared to the bath control. This increase in presynaptic vagal afferent calcium by the extract coincides with an increase in neurotransmitter release within the nucleus of the solitary tract, as the frequency of mEPSCs is significantly higher in the presence of the extract compared to the control. Finally, our imaging data show that hyperforin, a known component of St. John’s Wort extract, also significantly increases terminal calcium levels. Conclusion These data suggest that St. John’s Wort extract can significantly increase the probability of glutamate release from vagal afferents onto the NST by increasing presynaptic calcium. The in vitro vagal afferent synapse with NST neurons is an ideal model system to examine the mechanism of action of botanical agents on glutamatergic neurotransmission. PMID:24985104

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.

Ultrasound-Guided Phrenic Nerve Block for Intractable Hiccups following Placement of Esophageal Stent for Esophageal Squamous Cell Carcinoma.

PubMed

Arsanious, David; Khoury, Spiro; Martinez, Edgar; Nawras, Ali; Filatoff, Gregory; Ajabnoor, Hossam; Darr, Umar; Atallah, Joseph

2016-05-01

Hiccups are actions consisting of sudden contractions of the diaphragm and intercostals followed by a sudden inspiration and transient closure of the vocal cords. They are generally short lived and benign; however, in extreme and rare cases, such as esophageal carcinoma, they can become persistent or intractable, up to and involving significant pain, dramatically impacting the patient's quality of life. This case involves a 60-year-old man with a known history of squamous cell carcinoma of the esophagus. He was considered to have high surgical risk, and therefore he received palliative care through the use of fully covered metallic esophageal self-expandable stents due to a spontaneous perforated esophagus, after which he developed intractable hiccups and associated mediastinal pain. Conservative treatment, including baclofen, chlorpromazine, metoclopramide, and omeprazole, provided no relief for his symptoms. The patient was referred to pain management from gastroenterology for consultation on pain control. He ultimately received an ultrasound-guided left phrenic nerve block with bupivacaine and depomedrol, and 3 days later underwent the identical procedure on the right phrenic nerve. This led to complete resolution of his hiccups and associated mediastinal pain. At follow-up, 2 and 4 weeks after the left phrenic nerve block, the patient was found to maintain complete alleviation of the hiccups. Esophageal dilatation and/or phrenic or vagal afferent fiber irritation can be suspected in cases of intractable hiccups secondary to esophageal stenting. Regional anesthesia of the phrenic nerve through ultrasound guidance offers a long-term therapeutic option for intractable hiccups and associated mediastinal pain in selected patients with esophageal carcinoma after stent placement. Esophageal stent, esophageal stenting, intractable hiccups, intractable singultus, phrenic nerve block, phrenic nerve, ultrasound, palliative care, esophageal carcinoma.

Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

PubMed

Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2012-02-01

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.

Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs.

PubMed

Uemura, Kazunori; Inagaki, Masashi; Zheng, Can; Kawada, Toru; Li, Meihua; Fukumitsu, Masafumi; Sugimachi, Masaru

2017-04-01

Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n = 8, ivabradine group) or saline (n = 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac

Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

NASA Technical Reports Server (NTRS)

Damelio, F.; Gibbs, M. A.; Mehler, W. R.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

Fiber diameter distributions in the chinchilla's ampullary nerves

NASA Technical Reports Server (NTRS)

Hoffman, Larry F.; Honrubia, Vicente

2002-01-01

A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.5 to 8 microm. The distributions of diameters were positively skewed, where approximately 75% of the fibers were found to have diameters less than 3.5 microm. An analysis of the spatial distribution of diameters within the nerve section revealed that the lateralmost areas of the nerve contained larger fractions of fibers within the smallest diameter quintiles, and the central area harbored greater proportions of the larger diameter quintiles. However, significant fractions of all quintiles were found in all areas. These data were integrated with available data of Fernandez et al. (1998) to produce diameter estimates of calyx, dimorphic, and bouton morphology subpopulations. In view of a general relationship between diameter, innervation locus, and an afferent's physiologic characteristics, these data provide the basis for developing a perspective for the in situ distribution of afferent response dynamics.

Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model

NASA Astrophysics Data System (ADS)

Somann, Jesse P.; Albors, Gabriel O.; Neihouser, Kaitlyn V.; Lu, Kun-Han; Liu, Zhongming; Ward, Matthew P.; Durkes, Abigail; Robinson, J. Paul; Powley, Terry L.; Irazoqui, Pedro P.

2018-06-01

Objective. Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. Approach. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Main results. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. Significance. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.

Effect of mCOUP-TF1 deficiency on the glossopharyngeal and vagal sensory ganglia.

PubMed

Ichikawa, H; Lin, S-C; Tsai, S Y; Tsai, M-J; Sugimoto, T

2004-07-16

Immunohistochemistry for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase and calbindin D-28k was performed on the glossopharyngeal and vagal ganglia in mCOUP-TFI knockout mice to know the effect of its deficiency on different types of primary sensory neurons. In wild type and heterozygous mice, the glossopharyngeal and vagal ganglia contained abundant CGRP-, tyrosine hydroxylase- and calbindin D-28k-immunoreactive (IR) neurons. In the ganglia of mCOUP-TFI knockout mice, a 38% decrease of CGRP-IR neurons was detected. However, the number of tyrosine hydroxylase- or calbindin D-28k-neurons was not altered by the mCOUP-TFI deficiency. In the tongue of knockout mice, the number of CGRP-IR nerve fibers decreased compared to wild-type and heterozygous mice. The development of CGRP-IR petrosal neurons, which supply innervation of the tongue, may depend on mCOUP-TFI.

Domestic Violence and Vagal Reactivity to Peer Provocation

PubMed Central

Katz, Lynn Fainsilber

2007-01-01

This paper examined whether individual differences in children’s vagal reactivity to peer provocation was related to domestic violence within the family. It also examined the question of whether conduct-problem children who show vagal augmentation to peer provocation come from families with high levels of domestic violence. During the peer provocation, children were expecting to interact with a difficult peer while vagal reactivity was assessed. Groups were divided into children who showed vagal augmentation and vagal suppression to the stressful peer interaction. Findings indicated that conduct-problem children who showed vagal augmentation to interpersonal challenge came from families with the highest levels of domestic violence. Vagal augmentation was also associated with a greater number of conduct-related problems for those children exposed to high levels of domestic violence. Discussion highlights the role of individual differences in physiological reactivity in understanding children’s behavior problems in relation to domestic violence. PMID:17118516

Vagal tone during infant contingency learning and its disruption.

PubMed

Sullivan, Margaret Wolan

2016-04-01

This study used contingency learning to examine changes in infants' vagal tone during learning and its disruption. The heart rate of 160 five-month-old infants was recorded continuously during the first of two training sessions as they experienced an audiovisual event contingent on their pulling. Maternal reports of infant temperament were also collected. Baseline vagal tone, a measure of parasympathetic regulation of the heart, was related to vagal levels during the infants' contingency learning session, but not to their learner status. Vagal tone levels did not vary significantly over session minutes. Instead, vagal tone levels were a function of both individual differences in learner status and infant soothability. Vagal levels of infants who learned in the initial session were similar regardless of their soothability; however, vagal levels of infants who learned in a subsequent session differed as a function of soothability. Additionally, vagal levels during contingency disruption were significantly higher among infants in this group who were more soothable as opposed to those who were less soothable. The results suggest that contingency learning and disruption is associated with stable vagal tone in the majority of infants, but that individual differences in attention processes and state associated with vagal tone may be most readily observed during the disruption phase. © 2015 Wiley Periodicals, Inc.

Vagal Tone During Infant Contingency Learning and Its Disruption

PubMed Central

Sullivan, Margaret Wolan

2015-01-01

This study used contingency learning to examine changes in infants’ vagal tone during learning and its disruption. The heart rate of 160 five-month-old infants was recorded continuously during the first of two training sessions as they experienced an audiovisual event contingent on their pulling. Maternal reports of infant temperament were also collected. Baseline vagal tone, a measure of parasympathetic regulation of the heart, was related to vagal levels during the infants’ contingency learning session, but not to their learner status. Vagal tone levels did not vary significantly over session minutes. Instead, vagal tone levels were a function of both individual differences in learner status and infant soothability. Vagal levels of infants who learned in the initial session were similar regardless of their soothability; however, vagal levels of infants who learned in a subsequent session differed as a function of soothability. Additionally, vagal levels during contingency disruption were significantly higher among infants in this group who were more soothable as opposed to those who were less soothable. The results suggest that contingency learning and disruption is associated with stable vagal tone in the majority of infants, but that individual differences in attention processes and state associated with vagal tone may be most readily observed during the disruption phase. PMID:26517573

Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

NASA Technical Reports Server (NTRS)

Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

2002-01-01

Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

Allodynia mediated by C-tactile afferents in human hairy skin.

PubMed

Nagi, Saad S; Rubin, Troy K; Chelvanayagam, David K; Macefield, Vaughan G; Mahns, David A

2011-08-15

We recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz–200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s(−1))--known to excite CT fibres--was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4–6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected. Furthermore

Evidence for glutamatergic mechanisms in the vagal sensory pathway initiating cardiorespiratory reflexes in the shorthorn sculpin Myoxocephalus scorpius.

PubMed

Sundin, L; Turesson, J; Taylor, E W

2003-03-01

Glutamate is a major neurotransmitter of chemoreceptor and baroreceptor afferent pathways in mammals and therefore plays a central role in the development of cardiorespiratory reflexes. In fish, the gills are the major sites of these receptors, and, consequently, the terminal field (sensory area) of their afferents (glossopharyngus and vagus) in the medulla must be an important site for the integration of chemoreceptor and baroreceptor signals. This investigation explored whether fish have glutamatergic mechanisms in the vagal sensory area (Xs) that could be involved in the generation of cardiorespiratory reflexes. The locations of the vagal sensory and motor (Xm) areas in the medulla were established by the orthograde and retrograde axonal transport of the neural tract tracer Fast Blue following its injection into the ganglion nodosum. Glutamate was then microinjected into identified sites within the Xs in an attempt to mimic chemoreceptor- and baroreceptor-induced reflexes commonly observed in fish. By necessity, the brain injections were performed on anaesthetised animals that were fixed by 'eye bars' in a recirculating water system. Blood pressure and heart rate were measured using an arterial cannula positioned in the afferent branchial artery of the 3rd gill arch, and ventilation was measured by impedance probes sutured onto the operculum. Unilateral injection of glutamate (40-100 nl, 10 mmol l(-1)) into the Xs caused marked cardiorespiratory changes. Injection (0.1-0.3 mm deep) in different rostrocaudal, medial-lateral positions induced a bradycardia, either increased or decreased blood pressure, ventilation frequency and amplitude and, sometimes, an initial apnea. Often these responses occurred simultaneously in various different combinations but, occasionally, they appeared singly, suggesting specific projections into the Xs for each cardiorespiratory variable and local determination of the modality of the response. Response patterns related to

Oligosynaptic inhibition of group Ia afferents from brachioradialis to triceps brachii motor neurons in humans.

PubMed

Sato, Toshiaki; Nito, Mitsuhiro; Suzuki, Katsuhiko; Fujii, Hiromi; Hashizume, Wataru; Miyasaka, Takuji; Shindo, Masaomi; Naito, Akira

2018-01-01

This study examines effects of low-threshold afferents from the brachioradialis (BR) on excitability of triceps brachii (TB) motor neurons in humans. We evaluated the effects using a post stimulus time histogram (PSTH) and electromyogram averaging (EMG-A) methods in 13 healthy human participants. Electrical conditioning stimulation to the radial nerve branch innervating BR with the intensity below the motor threshold was delivered. In the PSTH study, the stimulation produced a trough (inhibition) in 36/69 TB motor units for all the participants. A cutaneous stimulation never provoked such inhibition. The central latency of the inhibition was 1.5 ± 0.5 ms longer than that of the homonymous facilitation. In the EMG-A study, the stimulation produced inhibition in EMG-A of TB in all participants. The inhibition diminished with a tonic vibration stimulation to BR. These findings suggest that oligosynaptic inhibition mediated by group Ia afferents from BR to TB exists in humans. Muscle Nerve 57: 122-128, 2018. © 2017 Wiley Periodicals, Inc.

Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph.

PubMed

Morishita, Koji; Costantini, Todd W; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

2014-03-01

Previous studies have established that posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory mediators, while the cellular basis of PHSML is less well characterized in acute models of injury. CD103 dendritic cells (DCs) have been identified in the mesenteric lymph (ML) in models of chronic intestinal inflammation, suggesting an important role in the gut response to injury. We have previously demonstrated the ability of vagal nerve stimulation (VNS) to prevent gut barrier failure after trauma/hemorrhagic shock (T/HS); however, the ability of VNS to alter ML DCs is unknown. We hypothesized that the CD103 MHC-II DC population would change in PHSML and that VNS would prevent injury-induced changes in this population in PHSML. Male Sprague-Dawley rats were randomly assigned to trauma/sham shock or T/HS. T/HS was induced by midline laparotomy and 60 minutes of HS (blood pressure, 35 mm Hg), followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. Gut tissue was harvested at 2 hours after injury for histologic analysis. ML was collected during the pre-HS, HS, and post-HS phase. For flow cytometric analysis, ML cells were subjected to staining with CD103 and MHC-II antibodies, and this cell population was compared in the pre-HS and post-HS phase from the same animal. The CD4Foxp3 cell (T reg) population in the ML node (MLN) was also tested to determine effects of CD103 DC modulation in the ML. VNS reduced histologic gut injury and ML flow seen after injury. The CD103 MHC-II DC population in the PHSML was significantly decreased compared with pre-HS and was associated with decreased T reg expression in the MLN. VNS prevented the injury-induced decrease in the CD103 MHC-II+ DC population in the ML and restored the T reg population in the MLN. These findings suggest that VNS mediates the inflammatory responses in ML DCs and MLN T reg cells by affecting the set point of T/HS responsiveness.

Tonic Investigation Concept of Cervico-vestibular Muscle Afferents

PubMed Central

Dorn, Linda Josephine; Lappat, Annabelle; Neuhuber, Winfried; Scherer, Hans; Olze, Heidi; Hölzl, Matthias

2016-01-01

Introduction Interdisciplinary research has contributed greatly to an improved understanding of the vestibular system. To date, however, very little research has focused on the vestibular system's somatosensory afferents. To ensure the diagnostic quality of vestibular somatosensory afferent data, especially the extra cranial afferents, stimulation of the vestibular balance system has to be precluded. Objective Sophisticated movements require intra- and extra cranial vestibular receptors. The study's objective is to evaluate an investigation concept for cervico-vestibular afferents with respect to clinical feasibility. Methods A dedicated chair was constructed, permitting three-dimensional trunk excursions, during which the volunteer's head remains fixed. Whether or not a cervicotonic provocation nystagmus (c-PN) can be induced with static trunk excursion is to be evaluated and if this can be influenced by cervical monophasic transcutaneous electrical nerve stimulation (c-TENS) with a randomized test group. 3D-video-oculography (VOG) was used to record any change in cervico-ocular examination parameters. The occurring nystagmuses were evaluated visually due to the small caliber of nystagmus amplitudes in healthy volunteers. Results The results demonstrate: no influence of placebo-controlled c-TENS on the spontaneous nystagmus; a significant increase of the vertical nystagmus on the 3D-trunk-excursion chair in static trunk flexion with cervical provocation in all young healthy volunteers (n = 49); and a significant difference between vertical and horizontal nystagmuses during static trunk excursion after placebo-controlled c-TENS, except for the horizontal nystagmus during trunk torsion. Conclusion We hope this cervicotonic investigation concept on the 3D trunk-excursion chair will contribute to new diagnostic and therapeutic perspectives on cervical pathologies in vestibular head-to-trunk alignment. PMID:28050208

The role of central 5-HT1A receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats

PubMed Central

Wang, Yun; Ramage, Andrew G

2001-01-01

Experiments were performed to determine whether 5-HT1A receptors (a) modulate the activity of cardiac and bronchoconstrictor vagal preganglionic neurones (CVPNs and BVPNs) in the nucleus ambiguus (NA) and (b) are involved in pulmonary C-fibre afferent-evoked excitation of CVPNs, by right-atrial injections of phenylbiguanide (PBG). These experiments were carried out on α-chloralose-anaesthetized, artificially ventilated and atenolol (1 mg kg−1)-pretreated cats. The ionophoretic application of 8-OH-DPAT (a selective 5-HT1A receptor agonist) influenced the activity of 16 of the 19 CVPNs tested. 8-OH-DPAT tended to cause inhibition at low currents (40 nA) and excitation at high currents (120 nA). The activity of 15 of these neurones increased in response to the application of 8-OH-DPAT. In six of the CVPNs tested, this excitatory action of 8-OH-DPAT was attenuated by co-application of the selective 5-HT1A receptor antagonist WAY-100635. The pulmonary C-fibre afferent-evoked excitation of eight CVPNs was attenuated by ionophoretic application of WAY-100635. In three out of four CVPNs, the ionophoretic application of PBG caused excitation. In five out of the nine identified BVPNs that were tested with ionophoretic application of 8-OH-DPAT, excitation was observed that was attenuated by WAY-100635. WAY-100635 (i.v. or intra-cisternally) also reversed bradycardia, hypotension and the decrease in phrenic nerve activity evoked by the i.v. application of 8-OH-DPAT (42 μg kg−1). In conclusion, the data indicate that 5-HT1A receptors located in the NA play an important role in the reflex activation of CVPNs and BVPNs, and support the view that overall, these receptors play a fundamental role in the reflex regulation of parasympathetic outflow. PMID:11691870

Two cases of Bezold-Jarisch reflex induced by intra-arterial nitroglycerin in critical left main coronary artery stenosis.

PubMed

Shah, Sachin P; Waxman, Sergio

2013-01-01

The Bezold-Jarisch reflex, a well-described phenomenon, occurs upon the stimulation of intracardiac mechanoreceptors and is mediated by vagal afferent nerve fibers. Several factors can sensitize the cardiovascular system to develop this reflex, including acute myocardial ischemia, natriuretic peptides, and, rarely, nitroglycerin administration in the setting of acute myocardial infarction. The development of the Bezold-Jarisch reflex in the presence of severe coronary artery stenosis, specifically left main coronary artery stenosis, has not been described. We report 2 cases of patients who underwent elective coronary angiography and were given intra-arterial nitroglycerin during radial sheath insertion to reduce radial artery spasm. In both patients, bradycardia and hypotension developed along with diaphoresis, consistent with the Bezold-Jarisch reflex. Coronary angiography revealed critical (>90%) left main coronary artery stenosis in both patients. Critical left main coronary artery stenosis might sensitize mechanoreceptors or vagal afferents to the development of the Bezold-Jarisch reflex after intra-arterial nitroglycerin use; however, the mechanism of this possible relationship is unclear. In addition to discussing our patients' cases, we review the medical literature relevant to the Bezold-Jarisch reflex.

An implantable nerve cooler for the exercising dog.

PubMed

Borgdorff, P; Versteeg, P G

1984-01-01

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

PubMed

Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

2016-05-01

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

[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.

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

PubMed

Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-05-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

PubMed Central

Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-01-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

Resting Vagal Tone and Vagal Response to Stress: Associations with Anxiety, Aggression and Perceived Anxiety Control among Youth

PubMed Central

Scott, Brandon G.; Weems, Carl F.

2014-01-01

This study tested the associations of both resting vagal tone and vagal response to stress with anxiety control beliefs, anxiety, and aggression among 80 youth (aged 11-17 years). Measures included physiological assessments of emotion regulation along with youth self-report of anxiety control beliefs, anxiety, and aggression and caregiver reports of their child's anxiety and aggression. Resting vagal tone was positively related to anxiety control beliefs, but negatively associated with anxiety. Conversely, higher levels of anxiety and aggression were associated with increased vagal tone during a cognitive stress task. Findings suggest associations between physiological and self-report of emotion regulation (anxiety control beliefs) and that anxiety and aggression may have specific and non-specific relations with physiological indices of emotion regulation. PMID:24708059

Parallel processing of afferent olfactory sensory information

PubMed Central

Vaaga, Christopher E.

2016-01-01

Key points The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood.One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation.Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons.Compared to external tufted cells, mitral cells have a prolonged afferent‐evoked EPSC, which serves to amplify the synaptic input.The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells.Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. Abstract Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1‐fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5‐fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic

Motor evoked potential monitoring of the vagus nerve with transcranial electrical stimulation during skull base surgeries.

PubMed

Ito, Eiji; Ichikawa, Masahiro; Itakura, Takeshi; Ando, Hitoshi; Matsumoto, Yuka; Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Sakuma, Jun; Saito, Kiyoshi

2013-01-01

Dysphasia is one of the most serious complications of skull base surgeries and results from damage to the brainstem and/or cranial nerves involved in swallowing. Here, the authors propose a method to monitor the function of the vagus nerve using endotracheal tube surface electrodes and transcranial electrical stimulation during skull base surgeries. Fifteen patients with skull base or brainstem tumors were enrolled. The authors used surface electrodes of an endotracheal tube to record compound electromyographic responses from the vocalis muscle. Motor neurons were stimulated using corkscrew electrodes placed subdermally on the scalp at C3 and C4. During surgery, the operator received a warning when the amplitude of the vagal motor evoked potential (MEP) decreased to less than 50% of the control level. After surgery, swallowing function was assessed clinically using grading criteria. In 5 patients, vagal MEP amplitude permanently deteriorated to less than 50% of the control level on the right side when meningiomas were dissected from the pons or basilar artery, or when a schwannoma was dissected from the vagal rootlets. These 5 patients had postoperative dysphagia. At 4 weeks after surgery, 2 patients still had dysphagia. In 2 patients, vagal MEPs of one side transiently disappeared when the tumors were dissected from the brainstem or the vagal rootlets. After surgery, both patients had dysphagia, which recovered in 4 weeks. In 7 patients, MEP amplitude was consistent, maintaining more than 50% of the control level throughout the operative procedures. After surgery all 7 patients were neurologically intact with normal swallowing function. Vagal MEP monitoring with transcranial electrical stimulation and endotracheal tube electrode recording was a safe and effective method to provide continuous real-time information on the integrity of both the supranuclear and infranuclear vagal pathway. This method is useful to prevent intraoperative injury of the brainstem

Coexistence of calbindin D-28k and NADPH-diaphorase in vagal and glossopharyngeal sensory neurons of the rat.

PubMed

Ichikawa, H; Helke, C J

1996-10-07

The presence and coexistence of calbindin D-28k-immunoreactivity (ir) and nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase activity (a marker of neurons that are presumed to convert L-arginine to L-citrulline and nitric oxide) were examined in the glossopharyngeal and vagal sensory ganglia (jugular, petrosal and nodose ganglia) of the rat. Calbindin D-28k-ir nerve cells were found in moderate and large numbers in the petrosal and nodose ganglia, respectively. Some calbindin D-28k-ir nerve cells were also observed in the jugular ganglion. NADPH-diaphorase positive nerve cells were localized to the jugular and nodose ganglia and were rare in the petrosal ganglion. A considerable portion (33-51%) of the NADPH-diaphorase positive neurons in these ganglia colocalized calbindin D-28k-ir. The presence and colocalization of calbindin D-28k-ir and NADPH-diaphorase activity in neurotransmitter-identified subpopulations of visceral sensory neurons were also studied. In all three ganglia, calcitonin gene-related peptide (CGRP)-ir was present in many NADPH-diaphorase positive neurons, a subset of which also contained calbindin D-28k-ir. In the nodose ganglion, many (42%) of tyrosine hydroxylase (TH)-ir neurons also contained NADPH diaphorase activity but did not contain calbindin D-28k-ir. These data are consistent with a potential co-operative role for calbindin D-28k and NADPH-diaphorase in the functions of a subpopulation of vagal and glossopharyngeal sensory neurons.

Police work stressors and cardiac vagal control.

PubMed

Andrew, Michael E; Violanti, John M; Gu, Ja K; Fekedulegn, Desta; Li, Shengqiao; Hartley, Tara A; Charles, Luenda E; Mnatsakanova, Anna; Miller, Diane B; Burchfiel, Cecil M

2017-09-10

This study examines relationships between the frequency and intensity of police work stressors and cardiac vagal control, estimated using the high frequency component of heart rate variability (HRV). This is a cross-sectional study of 360 officers from the Buffalo New York Police Department. Police stress was measured using the Spielberger police stress survey, which includes exposure indices created as the product of the self-evaluation of how stressful certain events were and the self-reported frequency with which they occurred. Vagal control was estimated using the high frequency component of resting HRV calculated in units of milliseconds squared and reported in natural log scale. Associations between police work stressors and vagal control were examined using linear regression for significance testing and analysis of covariance for descriptive purposes, stratified by gender, and adjusted for age and race/ethnicity. There were no significant associations between police work stressor exposure indices and vagal control among men. Among women, the inverse associations between the lack of support stressor exposure and vagal control were statistically significant in adjusted models for indices of exposure over the past year (lowest stressor quartile: M = 5.57, 95% CI 5.07 to 6.08, and highest stressor quartile: M = 5.02, 95% CI 4.54 to 5.51, test of association from continuous linear regression of vagal control on lack of support stressor β = -0.273, P = .04). This study supports an inverse association between lack of organizational support and vagal control among female but not male police officers. © 2017 Wiley Periodicals, Inc.

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.

PubMed

Chen, W; McRoberts, J A; Marvizón, J C G

2014-05-16

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. Published by Elsevier Ltd.

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

PubMed Central

Chen, Wenling; McRoberts, James A.; Marvizón, Juan Carlos G.

2014-01-01

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund’s adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. PMID:24583035

Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

PubMed

Ro, J Y; Capra, N F

2001-05-01

Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal afferents mediating the Bezold-Jarisch reflex

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

2000-01-01

The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) desensitize upon repeated exposure to selective agonists. BJR-mediated falls in heart rate, diastolic arterial blood pressure and cardiac output elicited by the 5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT (100 microg/kg, i.v.), progressively diminished upon repeated injection in conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly reduced in rats which had received the above injections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S-nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the injections of the 5-HT(3) receptor agonists. These findings suggest that tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5-HT(3) receptors on cardiopulmonary afferents rather than the impairment of the central or peripheral processing of the BJR.

Bicuculline and strychnine suppress the mesencephalic locomotor region-induced inhibition of group III muscle afferent input to the dorsal horn.

PubMed

Degtyarenko, A M; Kaufman, M P

2003-01-01

We examined the effect of iontophoretic application of bicuculline methiodide and strychnine hydrochloride on the mesencephalic locomotor region (MLR)-induced inhibition of dorsal horn cells in paralyzed cats. The activity of 60 dorsal horn cells was recorded extracellularly in laminae I, II, V-VII of spinal segments L7-S1. Each of the cells was shown to receive group III muscle afferent input as demonstrated by their responses to electrical stimulation of the tibial nerve (mean latency and threshold of activation: 20.1+/-6.4 ms and 15.2+/-1.4 times motor threshold, respectively). Electrical stimulation of the MLR suppressed transmission in group III muscle afferent pathways to dorsal horn cells. Specifically the average number of impulses generated by the dorsal horn neurons in response to a single pulse applied to the tibial nerve was decreased by 78+/-2.8% (n=60) during the MLR stimulation. Iontophoretic application (10-50 nA) of bicuculline and strychnine (5-10 mM) suppressed the MLR-induced inhibition of transmission of group III afferent input to laminae I and II cells by 69+/-5% (n=10) and 29+/-7% (n=7), respectively. Likewise, bicuculline and strychnine suppressed the MLR-induced inhibition of transmission of group III afferent input to lamina V cells by 59+/-13% (n=14) and 39+/-11% (n=10), respectively. Our findings raise the possibility that GABA and glycine release onto dorsal horn neurons in the spinal cord may play an important role in the suppression by central motor command of thin fiber muscle afferent-reflex pathways.

Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

PubMed Central

Miller, Jonas G.; Kahle, Sarah; Hastings, Paul D.

2016-01-01

Vagal tone is widely believed to be an important physiological aspect of emotion regulation and associated positive behaviors. However, there is inconsistent evidence for relations between children’s baseline vagal tone and their helpful or prosocial responses to others (Hastings & Miller, 2014). Recent work in adults suggests a quadratic association (inverted U-shape curve) between baseline vagal tone and prosociality (Kogan et al., 2014). The present research examined whether this nonlinear association was evident in children. We found consistent evidence for a quadratic relation between vagal tone and prosociality across 3 samples of children using 6 different measures. Compared to low and high vagal tone, moderate vagal tone in early childhood concurrently predicted greater self-reported prosociality (Study 1), observed empathic concern in response to the distress of others and greater generosity toward less fortunate peers (Study 2), and longitudinally predicted greater self-, mother-, and teacher-reported prosociality 5.5 years later in middle childhood (Study 3). Taken together, our findings suggest that moderate vagal tone at rest represents a physiological preparedness or tendency to engage in different forms of prosociality across different contexts. Early moderate vagal tone may reflect an optimal balance of regulation and arousal that helps prepare children to sympathize, comfort, and share with others. PMID:27819463

Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing)

PubMed Central

Laskawi, R.; Rohrbach, S.

2005-01-01

The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia. PMID:22073058

Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Cork, Simon C.; Eftekhar, Amir; Mirza, Khalid B.; Zuliani, Claudio; Nikolic, Konstantin; Gardiner, James V.; Bloom, Stephen R.; Toumazou, Christofer

2018-02-01

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.

Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

PubMed

Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H

2017-05-01

Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed

The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve.

PubMed

Liddy, Whitney; Barber, Samuel R; Cinquepalmi, Matteo; Lin, Brian M; Patricio, Stephanie; Kyriazidis, Natalia; Bellotti, Carlo; Kamani, Dipti; Mahamad, Sadhana; Dralle, Henning; Schneider, Rick; Dionigi, Gianlorenzo; Barczynski, Marcin; Wu, Che-Wei; Chiang, Feng Yu; Randolph, Gregory

2017-03-01

Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. Retrospective chart review. Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 μV (mean difference range = -814.1 to -1,078 μV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 μV (mean difference range = -6,222.6 to -6,362.3 μV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. 4

Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.

PubMed

Phillis, Benjamin D; Martin, Chris M; Kang, Daiwu; Larsson, Håkan; Lindström, Erik A; Martinez, Vicente; Blackshaw, L Ashley

2009-08-07

The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

PubMed Central

Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent

Effects of vagal deafferentation on oesophageal motility and transit in the sheep.

PubMed Central

Falempin, M; Madhloum, A; Rousseau, J P

1986-01-01

Effects of vagal deafferentation on oesophageal motility and transit were studied in conscious sheep by recording the electromyographic activity of different parts of oesophagus during swallowing of saliva, or balloons inflated with 20 ml of air. Surgical isolation and subsequent sectioning of the nodose ganglion, leaving the bundles of motor fibres intact, can be performed in sheep. Division of both ganglia led to immediate death of sheep. However, vagal deafferentation of the thoracic oesophagus could be achieved by sectioning the thoracic vagus nerve in association with sectioning the contralateral nodose ganglion. The sectioning of one vagus nerve did not affect primary oesophageal peristalsis during swallowing of saliva or of a bolus. Balloons inflated in the pharyngeal cavity and left free to move caudally, failed to pass into the stomach within the normal time of 2-2.3 s in only 4-16% of the tests. In these cases, they were always stopped in the thoracic oesophagus. Following total deafferentation of the thoracic oesophagus, balloons were prevented from being propelled into the stomach in each test. They were stopped for several minutes at the beginning of the deafferented part of the oesophagus. Electromyographic activity recorded from the deafferented part was reduced during swallowing of balloons or saliva. Deafferentation was confirmed by the failure of the presumed deafferented segment of oesophagus to respond to distension. These experiments provide direct evidence that the vagus carries information from the oesophagus which influences the central pattern generator during swallowing of a bolus or saliva. In sheep, this feed-back is essential for the effective swallowing of a bolus although not for saliva. PMID:3723412

Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

PubMed Central

Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2008-01-01

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

PubMed Central

Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

2016-01-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

PubMed Central

Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

2014-01-01

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models.

PubMed

Takada, M; Nishida, K; Kataoka-Kato, A; Gondo, Y; Ishikawa, H; Suda, K; Kawai, M; Hoshi, R; Watanabe, O; Igarashi, T; Kuwano, Y; Miyazaki, K; Rokutan, K

2016-07-01

This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN. © 2016 John Wiley & Sons Ltd.

Wavelet Packet Analysis for Angular Data Extraction from Muscle Afferent Cuff Electrode Signals

DTIC Science & Technology

2001-10-25

from rabbits. In order to estimate ankle flexion/extension angles, we recorded ENG signals from the left Tibial and Peroneal nerves, both during FES...afferent ENG. II. METHODOLOGY A. Experimental Setup Acute experiments were conducted with 2 female New Zealand rabbits. The rabbits were pre-anesthetized...fixating the knee and ankle joints in place (see [3] for more details) . For extracting the ENG signals, tripolar cuff electrodes were implanted onto the

Cortical presynaptic control of dorsal horn C-afferents in the rat.

PubMed

Moreno-López, Yunuen; Pérez-Sánchez, Jimena; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

PubMed Central

Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

Ionotropic and metabotropic receptor mediated airway sensory nerve activation.

PubMed

Lee, Min-Goo; Kollarik, Marian; Chuaychoo, Benjamas; Undem, Bradley J

2004-01-01

There are several receptors capable of inducing activating generator potentials in cough-associated afferent terminals in the airways. The chemical receptors leading to generator potentials can be subclassified into ionotropic and metabotropic types. An ionotropic receptor has an agonist-binding domain, and also serves directly as an ion channel that is opened upon binding of the agonist. Examples of ionotropic receptors found in airway sensory nerve terminals include receptors for serotonin (5-HT3 receptors), ATP (P2X receptors), acetylcholine (nicotinic receptors), receptors for capsaicin and related vanilloids (TRPV1 receptors), and acid receptors (acid sensing ion channels). Afferent nerve terminals can also be depolarized via activation of metabotropic or G-protein coupled receptors (GPCRs). Among the GPCRs that can lead to activation of airway afferent fibers include bradykinin B2 and adenosine A1 receptors. The signaling events leading to GPCR-mediated membrane depolarization are more complex than that seen with ionotropic receptors. The GPCR-mediated effects are thought to occur through classical second messenger systems such as activation of phospholipase C. This may lead to membrane depolarization through interaction with specific ionotropic receptors (such as TRPV1) and/or various types of calcium activated channels.

Common theme for drugs effective in overactive bladder treatment: Inhibition of afferent signaling from the bladder

PubMed Central

Hood, Brandy; Andersson, Karl-Erik

2013-01-01

The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed. PMID:23072271

Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

PubMed Central

Titus-Mitchell, Haley E.; Bullinger, Katie L.; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C.

2011-01-01

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons. PMID:21832035

Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

PubMed

Baev, K V; Esipenko, V B; Shimansky YuP

1991-01-01

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just

Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

PubMed

Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

2003-09-01

The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

Function and morphology correlates of rectal nerve mechanoreceptors innervating the guinea pig internal anal sphincter.

PubMed

Lynn, P A; Brookes, S J H

2011-01-01

Mechanoreceptors to the internal anal sphincter (IAS) contribute to continence and normal defecation, yet relatively little is known about their function or morphology. We investigated the function and structure of mechanoreceptors to the guinea pig IAS. Extracellular recordings from rectal nerve branches to the IAS in vitro, combined with anterograde labeling of recorded nerve trunks, were used to characterize extrinsic afferent nerve endings activated by circumferential distension. Slowly adapting, stretch-sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were silent under basal conditions and responded to circumferential stretch in a saturating linear manner. Rectal nerve afferents responded to compression with von Frey hairs with low thresholds (0.3-0.5 mN) and 3.4 ± 0.5 discrete, elongated mechanosensitive fields of innervation aligned parallel to circular muscle bundles (length = 62 ± 16 mm, n = 10). Anterogradely labeled rectal nerve axons typically passed through sparse irregular myenteric ganglia adjacent to the IAS, before ending in extensive varicose arrays within the circular muscle and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS myenteric ganglia contained intraganglionic laminar endings. In eight preparations, mechanotransduction sites were mapped in combination with successful anterograde fills. Mechanotransduction sites were strongly associated with extensive fine varicose arrays within the circular muscle (P < 0.05), and not with any other neural structures. Mechanotransduction sites for low-threshold, slowly adapting mechanoreceptors innervating the IAS are likely to correspond to extensive fine varicose arrays within the circular muscle. © 2010 Blackwell Publishing Ltd.

Hydrogen peroxide preferentially activates capsaicin-sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder.

PubMed

Nicholas, S; Yuan, S Y; Brookes, S J H; Spencer, N J; Zagorodnyuk, V P

2017-01-01

There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H 2 O 2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. H 2 O 2 (300-1000 μM) preferentially and potently activated capsaicin-sensitive high threshold afferents but not low threshold stretch-sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin-sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC-030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N-(2-aminoethyl)-N-[[3-methoxy-4-(phenylmethoxy)phenyl]methyl]thiophene-2-carboxamide, significantly inhibited the H 2 O 2 -induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H 2 O 2 on high threshold afferents. The findings show that H 2 O 2 , in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long-lasting activation of the majority of capsaicin-sensitive high threshold afferents, but not low threshold stretch-sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin-sensitive afferent fibres are probable targets of ROS released during oxidative stress. © 2016 The British Pharmacological Society.

Hydrogen peroxide preferentially activates capsaicin‐sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder

PubMed Central

Nicholas, S; Yuan, S Y; Brookes, S J H; Spencer, N J

2016-01-01

Background and Purpose There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. Experimental Approach ‘Close‐to‐target’ single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. Key Results H2O2 (300–1000 μM) preferentially and potently activated capsaicin‐sensitive high threshold afferents but not low threshold stretch‐sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin‐sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC‐030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N‐(2‐aminoethyl)‐N‐[[3‐methoxy‐4‐(phenylmethoxy)phenyl]methyl]thiophene‐2‐carboxamide, significantly inhibited the H2O2‐induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H2O2 on high threshold afferents. Conclusions and Implications The findings show that H2O2, in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long‐lasting activation of the majority of capsaicin‐sensitive high threshold afferents, but not low threshold stretch‐sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin‐sensitive afferent fibres are probable targets of ROS released during oxidative stress. PMID:27792844

Selective Expression of a Sodium Pump Isozyme by Cough Receptors and Evidence for Its Essential Role in Regulating Cough

PubMed Central

Mazzone, Stuart B.; Reynolds, Sandra M.; Mori, Nanako; Kollarik, Marian; Farmer, David G.; Myers, Allen C.

2009-01-01

We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na+-K+ ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the α3 subunit of Na+-K+ ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo are potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation. PMID:19864578

Effect of Microgravity on Afferent Innervation

NASA Technical Reports Server (NTRS)

1998-01-01

Presentations and publications are: (1) an audiovisual summary web presentation on results from SLM-MIR avian experiments. A color presentation summarizing results from the SLM-MIR and STS-29 avian experiments; (2) color threshold and ratio of S 100B MAP5, NF68/200, GABA and GAD; (3) chicken (Gallus domesticus) inner ear afferents; (4) microgravity in the STS-29 Space Shuttle Discovery affected the vestibular system of chick embryos; (5) expression of S 100B in sensory and secretory cells of the vertebrate inner ear; (6) otoconia biogenesis, phylogeny, composition and functional attributes;(7) the glycan keratin sulfate in inner ear crystals; (8) elliptical-P cells in the avian perilymphatic interface of the tegmentum vasculosum; and (9) LAMP2c and S100B upregulation in brain stem after VIIIth nerve deafferentation.

Importance of vagal input in maintaining gastric tone in the dog.

PubMed Central

Azpiroz, F; Malagelada, J R

1987-01-01

1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels. Images Fig. 1 PMID:2888879

The role of the vagus nerve in the generation of cardiorespiratory interactions in a neotropical fish, the pacu, Piaractus mesopotamicus.

PubMed

Leite, Cleo Alcantara Costa; Taylor, E W; Guerra, C D R; Florindo, L H; Belão, T; Rantin, F T

2009-08-01

The role of the vagus nerve in determining heart rate (f(H)) and cardiorespiratory interactions was investigated in a neotropical fish, Piaractus mesopotamicus. During progressive hypoxia f(H) initially increased, establishing a 1:1 ratio with ventilation rate (f(R)). Subsequently there was a hypoxic bradycardia. Injection of atropine abolished a normoxic inhibitory tonus on the heart and the f(H) adjustments during progressive hypoxia, confirming that they are imposed by efferent parasympathetic inputs via the vagus nerve. Efferent activity recorded from the cardiac vagus in lightly anesthetized normoxic fish included occasional bursts of activity related to spontaneous changes in ventilation amplitude, which increased the cardiac interval. Restricting the flow of aerated water irrigating the gills resulted in increased respiratory effort and bursts of respiration-related activity in the cardiac vagus that seemed to cause f(H) to couple with f(R). Cell bodies of cardiac vagal pre-ganglionic neurons were located in two distinct groups within the dorsal vagal motor column having an overlapping distribution with respiratory motor-neurons. A small proportion of cardiac vagal pre-ganglionic neurons (2%) was in scattered positions in the ventrolateral medulla. This division of cardiac vagal pre-ganglionic neurons into distinct motor groups may relate to their functional roles in determining cardiorespiratory interactions.

Afferent connections of nervus facialis and nervus glossopharyngeus in the pigeon (Columba livia) and their role in feeding behavior.

PubMed

Dubbeldam, J L

1984-01-01

The afferent connections of the facial nerve and glossopharyngeal nerve in the pigeon have been studied with the Fink-Heimer I method after ganglion lesions. The nucleus ventrolateralis anterior of the solitary complex and an indistinct cell group S VII medial to the nucleus interpolaris of the descending trigeminal tract are the terminal fields for facial afferents. The n. ventrolateralis anterior also receives an important projection from the distal glossopharyngeal ganglion. Other projection areas of this ganglion are the n. presulcalis , n. centralis anterior, n. intermedius anterior and the parasolitary nucleus. Both ganglia have only ipsilateral projections. A lesion in the jugular ganglion complex causes degeneration throughout the ipsilateral solitary complex, in the contralateral n. commissuralis and n. centralis posterior and in the n. cuneatus externus. The lack of a substantial contribution to the trigeminal system is ascribed to the absence of mechanoreceptors in the tongue. The implications for the organization of neuronal pathways related to the feeding behavior are discussed.

Interparental Relationship Dynamics and Cardiac Vagal Functioning in Infancy

PubMed Central

Graham, Alice M.; Ablow, Jennifer C.; Measelle, Jeffrey R.

2010-01-01

This study examined associations between interparental relationship dynamics and vagus system functioning in infancy. The functioning of the vagus system, part of the parasympathetic nervous system, indexes emotional reactivity and regulation. Interparental avoidance and dyadic adjustment constitute the focus of this study in order to bring attention to relationship dynamics not subsumed under overt conflict. Infants’ baseline vagal tone and change in vagal tone in response to a novel toy were assessed at five months in a sample of high-risk mother-infant dyads (n = 77). Maternal report of interparental avoidance demonstrated an association with infants’ baseline vagal tone, while interparental dyadic adjustment was associated with change in infants’ vagal tone from baseline to the novel toy. Infant gender moderated these associations. Maternal sensitivity did not mediate interparental relationship dynamics and infants’ vagal functioning. Results are discussed in the context of emotional security theory. PMID:20727595

Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

PubMed

Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

2012-11-10

Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects.

PubMed

De Couck, M; Cserjesi, R; Caers, R; Zijlstra, W P; Widjaja, D; Wolf, N; Luminet, O; Ellrich, J; Gidron, Y

2017-03-01

The vagus nerve is strategically located in the body, and has multiple homeostatic and health-promoting effects. Low vagal activity predicts onset and progression of diseases. These are the reasons to activate this nerve. This study examined the effects of transcutaneous vagus nerve stimulation (t-VNS) on a main index of vagal activity, namely heart rate variability (HRV). In Study 1, we compared short (10min) left versus right ear t-VNS versus sham (no stimulation) in a within-subjects experimental design. Results revealed significant increases in only one HRV parameter (standard deviation of the RR intervals (SDNN)) following right-ear t-VNS. Study 2 examined the prolonged effects of t-VNS (1h) in the right ear. Compared to baseline, right-t-VNS significantly increased the LF and LF/HF components of HRV, and SDNN in women, but not in men. These results show limited effects of t-VNS on HRV, and are discussed in light of neuroanatomical and statistical considerations and future directions are proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

Anatomic assessment of sympathetic peri-arterial renal nerves in man.

PubMed

Sakakura, Kenichi; Ladich, Elena; Cheng, Qi; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Fowler, David R; Kolodgie, Frank D; Virmani, Renu; Joner, Michael

2014-08-19

Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood. The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p < 0.001). The mean number of nerves in the ventral region (11.0 ± 3.5 per section) was greater compared with the dorsal region (6.2 ± 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene-related peptide ratio 25.1 ± 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients. The density of peri-arterial renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures. Copyright © 2014

Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues.

PubMed

Darques, J L; Jammes, Y

1997-03-07

Recordings of group IV afferent activity of tibialis anterior muscle were performed in paralysed rabbits during runs of electrically induced fatigue produced by direct muscle stimulation at a high (100 Hz, high-frequency fatigue HFF) or a low rate (10 Hz, low-frequency fatigue LFF). In addition to analysis of afferent nerve action potentials, muscle force and compound muscle action potentials (M waves) elicited by direct muscle stimulation with single shocks were recorded. Changes in M wave configuration were used as an index of the altered propagation of membrane potentials and the associated efflux of potassium from muscle fibers. The data show that increased group IV afferent activity occurred during LFF as well as HFF trials and developed parallel with force failure. Enhanced afferent activity was significantly higher during LFF (maximal delta f(impulses) = 249 +/- 35%) than HFF (147 +/- 45%). No correlation was obtained between the responses of group IV afferents to LFF or to pressure exerted on tibialis anterior muscle. On the other hand, decreased M wave amplitude was minimal with LFF while it was pronounced with HFF. Close correlations were found between fatigue-induced activation of group IV afferents and decreases in force or M wave amplitude, but their strength was significantly higher with LFF compared to HFF. Thus, electrically induced fatigue activates group IV muscle afferents with a prominent effect of low-frequency stimulation. The mechanism of muscle afferent stimulation does not seem to be due to the sole increase in extracellular potassium concentration, but also by the efflux of muscle metabolites, present during fatiguing contractions at low rate of stimulation.

Ankle joint movements are encoded by both cutaneous and muscle afferents in humans.

PubMed

Aimonetti, Jean-Marc; Roll, Jean-Pierre; Hospod, Valérie; Ribot-Ciscar, Edith

2012-08-01

We analyzed the cutaneous encoding of two-dimensional movements by investigating the coding of movement velocity for differently oriented straight-line movements and the coding of complex trajectories describing cursive letters. The cutaneous feedback was then compared with that of the underlying muscle afferents previously recorded during the same "writing-like" movements. The unitary activity of 43 type II cutaneous afferents was recorded in the common peroneal nerve in healthy subjects during imposed ankle movements. These movements consisted first of ramp-and-hold movements imposed at two different and close velocities in seven directions and secondly of "writing-like" movements. In both cases, the responses were analyzed using the neuronal population vector model. The results show that movement velocity encoding depended on the direction of the ongoing movement. Discriminating between two velocities therefore involved processing the activity of afferent populations located in the various skin areas surrounding the moving joint, as shown by the statistically significant difference observed in the amplitude of the sum vectors. Secondly, "writing-like" movements induced cutaneous neuronal patterns of activity, which were reproducible and specific to each trajectory. Lastly, the "cutaneous neuronal trajectories," built by adding the sum vectors tip-to-tail, nearly matched both the movement trajectories and the "muscle neuronal trajectories," built from previously recorded muscle afferents. It was concluded that type II cutaneous and the underlying muscle afferents show similar encoding properties of two-dimensional movement parameters. This similarity is discussed in relation to a central gating process that would for instance increase the gain of cutaneous inputs when muscle information is altered by the fusimotor drive.

Monosynaptic convergence of chorda tympani and glossopharyngeal afferents onto ascending relay neurons in the nucleus of the solitary tract: A high-resolution confocal and correlative electron microscopy approach

PubMed Central

Corson, James A.; Erisir, Alev

2014-01-01

While physiological studies suggested convergence of chorda tympani and glossopharyngeal afferent axons onto single neurons of the rostral nucleus of the solitary tract (rNTS), anatomical evidence has been elusive. The current study uses high-magnification confocal microscopy to identify putative synaptic contacts from afferent fibers of the two nerves onto individual projection neurons. Imaged tissue is re-visualized with electron microscopy, confirming that overlapping fluorescent signals in confocal z-stacks accurately identify appositions between labeled terminal and dendrite pairs. Monte Carlo modeling reveals that the probability of overlapping fluorophores is stochastically unrelated to the density of afferent label suggesting that convergent innervation in the rNTS is selective rather than opportunistic. Putative synaptic contacts from each nerve are often compartmentalized onto dendrite segments of convergently innervated neurons. These results have important implications for orosensory processing in the rNTS, and the techniques presented here have applications in investigations of neural microcircuitry with an emphasis on innervation patterning. PMID:23640852

Vagal tone as an index of mental state

NASA Technical Reports Server (NTRS)

Porges, Stephen W.

1988-01-01

The utility of monitoring oscillations in the heart rate pattern as a window to the brain is discussed as an index of general central nervous system status. Quantification of the amplitude of respiratory sinus arrhythmia provides an accurate index of cardiac vagal tone. A number of studies have demonstrated the validity of this measure; the relationship between flight performance and vagal tone has also been studied. In general, the vagal tone index appears to monitor global states of the central nervous system and may be useful in screening the general state of pilots.

Cardiac Vagal Regulation and Early Peer Status

ERIC Educational Resources Information Center

Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.

2007-01-01

A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

Activation of normal and inflamed fine articular afferent units by serotonin.

PubMed

Herbert, M K; Schmidt, R F

1992-07-01

In cats anesthetized with alpha-chloralose, extracellular recordings were made from fine afferent units belonging to the medial articular nerve (MAN) of the knee joint. The excitatory and sensitizing effects on articular afferents of serotonin (5-HT) applied intra-arterially close to the joint were examined. The joints were either normal or an experimental arthritis had been induced some hours before the recording session. Bolus injections of 1.35-135 micrograms 5-HT excited about 43% of group III (CV: 2.5-20 m/sec) and 73% of group IV units (CV: less than 2.5 m/sec) from normal joints. The latency was usually between 10 and 30 sec, and the duration and size of the responses were dose-dependent. Fast group III units (CV: greater than 16 m/sec) and group II units (CV: greater than 20 m/sec) were never excited by 5-HT. Repetitive administration led to pronounced tachyphylaxis of the 5-HT response. Inflammation induced an enhanced sensitivity of group III articular afferent units to close intra-arterial application of 5-HT. In particular the total duration of each response was considerably prolonged (4-10 min against 1-2 min under normal conditions). At the same time the tachyphylaxis seen under normal conditions was greatly reduced. In contrast, group IV articular afferent units did not become sensitized to 5-HT in the course of inflammation. In normal joints 5-HT did not sensitize fine afferent units for movement-induced responses. However, after inflammation, a distinct sensitization to such movements by 5-HT application could be observed both in group III and group IV fiber ranges. The sensitization had a short time course not exceeding 7 min. The tonic component of the movement-induced response was more enhanced than the phasic one. The bolus application of 5-HT led to temporary vasoconstriction of the knee joint vessels. This vasoconstriction was especially pronounced in inflamed joints and impeded the access of subsequently applied substances to the terminal

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed Central

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-01-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-03-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

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.

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius.

PubMed

Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2018-01-30

Stimulation of vagal afferent endings with intravenous phenylbiguanide (PBG) causes both bradycardia and vasodepression, simulating neurally mediated syncope. Activation of µ-opioid receptors in the nucleus tractus solitarius (NTS) increases blood pressure. Electroacupuncture (EA) stimulation of somatosensory nerves underneath acupoints P5-6, ST36-37, LI6-7 or G37-39 selectively but differentially modulates sympathoexcitatory responses. We therefore hypothesized that EA-stimulation at P5-6 or ST36-37, but not LI6-7 or G37-39 acupoints, inhibits the bradycardia and vasodepression through a µ-opioid receptor mechanism in the NTS. We observed that stimulation at acupoints P5-6 and ST36-37 overlying the deep somatosensory nerves and LI6-7 and G37-39 overlying cutaneous nerves differentially evoked NTS neural activity in anesthetized and ventilated animals. Thirty-min of EA-stimulation at P5-6 or ST36-37 reduced the depressor and bradycardia responses to PBG while EA at LI6-7 or G37-39 did not. Congruent with the hemodynamic responses, EA at P5-6 and ST36-37, but not at LI6-7 and G37-39, reduced vagally evoked activity of cardiovascular NTS cells. Finally, opioid receptor blockade in the NTS with naloxone or a specific μ-receptor antagonist reversed P5-6 EA-inhibition of the depressor, bradycardia and vagally evoked NTS activity. These data suggest that point specific EA stimulation inhibits PBG-induced vasodepression and bradycardia responses through a μ-opioid mechanism in the NTS.

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.

PubMed

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-12-15

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

PubMed Central

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-01-01

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)−1) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to −0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of l-glutamate at the same sites, and both the effects of l-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

Effect of peripheral nerve injury on receptive fields of cells in the cat spinal cord.

PubMed

Devor, M; Wall, P D

1981-06-20

When the sciatic and saphenous nerves are cut and ligated in adult cats, the immediate effect is the production of a completely anesthetic foot and a region in medial lumbar dorsal horn where almost all cells have lost their natural receptive fields (RFs). Beginning at about 1 week and maturing by 4 weeks, some 40% of cells in the medial dorsal horn gain a novel RF on proximal skin, that is, upper and lower leg, thigh, lower back, or perineum. This new RF is supplied by intact proximal nerves and not by sciatic and saphenous nerve fibers that sprouted in the periphery. During the period of switching of RFs from distal to proximal skin there was no gross atrophy of dorsal horn grey matter and no Fink-Heimer stainable degeneration of central arbors and terminals of peripherally axotomized afferents. In intact animals medial dorsal horn cells showed no sign of response to mechanical stimulation of proximal skin. RFs of some of the cells had spontaneous variations in size and sensitivity, but these were not nearly sufficient to explain the large shifts observed after chronic nerve section. Tetanic electrical stimulation of skin or peripheral nerves often caused RFs to shrink, but never to expand. Although natural stimuli of proximal skin would not excite medial dorsal horn cells in intact or acutely deafferented animals, it was found that electrical stimulation of proximal nerves did excite many of these cells, often at short latencies. In the discussion we justify our working hypothesis that the appearance of novel RFs is due to the strengthening or unmasking of normally present but ineffective afferent terminals, rather than to long-distance sprouting of new afferent arbors within the spinal cord.

Interpretation of fusimotor activity in cat masseter nerve during reflex jaw movements.

PubMed Central

Gottlieb, S; Taylor, A

1983-01-01

Simultaneous recordings were made from fusimotor axons in the central ends of filaments of the masseter nerve, and from masseter and temporalis spindle afferents in the mesencephalic nucleus of the fifth cranial nerve in lightly anaesthetized cats. Fusimotor and alpha-motor units in the masseter nerve were differentiated on the basis of their response to passive ramp and hold stretches applied to the jaw. Spindle afferents were identified as primary or secondary according to their dynamic index after administration of suxamethonium. The activity of a given fusimotor unit during reflex movements of the jaw followed one of two distinct patterns: so-called 'tonic' units showed a general increase in activity during a movement, without detailed relation to lengthening or shortening, while 'modulated' units displayed a striking modulation of their activity with shortening, and were usually silent during subsequent lengthening. Comparison of the simultaneously recorded fusimotor and spindle afferent activity suggests that modulated units may be representative of a population of static fusimotor neurones, and tonic units of a population of dynamic fusimotor neurones. In these lightly anaesthetized animals, both primary and secondary spindle afferents showed increased firing during muscle shortening as well as during lengthening. This increase during shortening is not usually seen in conscious animals and reasons are given for the view that it is due to greater depression of alpha-motor activity than of static fusimotor activity during anaesthesia. The results are discussed in relation to the theories of 'alpha-gamma co-activation' and of 'servo-assistance'; and it is suggested that static fusimotor neurones provide a 'temporal template' of the intended movement, while dynamic fusimotor neurones set the required dynamic sensitivity to deviations from the intended movement pattern. PMID:6229627

Spinal cord stimulation paresthesia and activity of primary afferents.

PubMed

North, Richard B; Streelman, Karen; Rowland, Lance; Foreman, P Jay

2012-10-01

A patient with failed back surgery syndrome reported paresthesia in his hands and arms during a spinal cord stimulation (SCS) screening trial with a low thoracic electrode. The patient's severe thoracic stenosis necessitated general anesthesia for simultaneous decompressive laminectomy and SCS implantation for chronic use. Use of general anesthesia gave the authors the opportunity to characterize the patient's unusual distribution of paresthesia. During SCS implantation, they recorded SCS-evoked antidromic potentials at physiologically relevant amplitudes in the legs to guide electrode placement and in the arms as controls. Stimulation of the dorsal columns at T-8 evoked potentials in the legs (common peroneal nerves) and at similar thresholds, consistent with the sensation of paresthesia in the arms, in the right ulnar nerve. The authors' electrophysiological observations support observations by neuroanatomical specialists that primary afferents can descend several (in this case, at least 8) vertebral segments in the spinal cord before synapsing or ascending. This report thus confirms a physiological basis for unusual paresthesia distribution associated with thoracic SCS.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

PubMed

Zhang, Youhua; Popović, Zoran B; Kusunose, Kenya; Mazgalev, Todor N

2013-01-01

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF. © 2012 Wiley Periodicals, Inc.

Serotonin modulates substance P-induced plasma extravasation and vasodilatation in rat skin by an action through capsaicin-sensitive primary afferent nerves.

PubMed

Khalil, Z; Helme, R D

1990-09-17

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine the ability of serotonin (5-HT) to modulate an inflammatory reaction manifested as plasma extravasation and vasodilatation induced by the neuropeptide substance P (SP). In addition, the role of primary afferent sensory nerve fibres in these modulatory effects was studied in capsaicin pretreated rats. Using a protocol of simultaneous perfusion of amine and peptide over the blister base, no major modulatory effect was observed. On the other hand, using a protocol of sequential perfusion, 5-HT was found to extend the plasma extravasation and vasodilatation responses to SP. 5-HT maintained the plasma extravasation response to SP after cessation of stimulation (during the post-stimulation period). On the other hand, it extended the vasodilatation response to SP during the actual stimulation period by preventing the occurrence of tachyphylaxis. These modulatory effects were absent in capsacin-pretreated rats. The present study provides evidence for the first time in vivo to suggest that serotonin can modulate an inflammatory response to SP via a mechanism that involves capsaicin-sensitive sensory fibres.

Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the tractus solitarius: roles in the baroreceptor reflex.

PubMed

Massari, V J; Shirahata, M; Johnson, T A; Lauenstein, J M; Gatti, P J

1998-03-02

Physiological and light microscopic evidence suggest that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; however, ultrastructural support for this hypothesis is lacking. We have traced the central projections of the carotid sinus nerve (CSN) in the cat by utilizing the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the histochemical visualization of transganglionically labeled CSN afferents and for the immunocytochemical visualization of SP by dual labeling light and electron microscopic methods. Either HRP or SP was readily identified in single-labeled unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP immunoreactivity was also identified in unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS, which were simultaneously identified as CSN primary afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive for SP. Therefore, while the ultrastructural data support the hypothesis that SP immunoreactive first-order neurons are involved in the origination of the baroreceptor reflex, they suggest that only a modest part of the total sensory input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these synapses. Furthermore, SP terminals were never observed to form the presynaptic element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not appear to be involved in the modulation of the baroreceptor reflex in the dlNTS. Copyright 1998 Elsevier Science B.V.

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

PubMed Central

Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

2013-01-01

The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans.

PubMed

Cui, Jian; McQuillan, Patrick M; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

2012-08-15

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

[Roles of biologically active peptide in regulation of feeding behavior and energy homeostasis].

PubMed

Sakurai, Takeshi

2003-09-01

The mechanisms for regulating food intake involve a complicated interplay between peripheral systems (including gastrointestinal peptide secretion, leptin, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. Many hypothalamic neuropeptides are involved in the regulation of energy homeostasis and feeding behavior, including melanocortins, Agouti-related peptide, neuropeptide-Y, cocaine, and amphetamine-regulated transcript, orexin, and melanine concentrating hormone (MCH) as well as monamines (serotonin, dopamine, norepinephrine). Many of these systems are regulated by peripheral metabolic cues including plasma leptin levels. This review summarizes roles of neuropeptides in the regulatory mechanism of feeding and energy homeostasis.

Increased Vagal Tone and Sleep Apnea Syndrome.

PubMed

Ahmed, Tosaddak

2016-01-01

It has been observed that atrial overdrive pacing abolishes sleep apnea syndrome, but how it does so has not been explained. There is a possibility that it sends a retrograde inhibitory impulse to the vagal center in the brainstem, which in turn reduces the vagal tone, and thus prevents sleep apnea. Therefore, medical vagolytics such as atropine type of drugs should have the same effect. This is a case report of such an attempt.

Effect of vagotomy and vagal cooling on bronchoconstrictor response to substance P in sheep.

PubMed

Corcoran, B M; Haigh, A L

1995-10-01

The bronchoconstrictor effect of intravenous substance P can be antagonised by atropine pre-treatment in several species, and we have previously reported this finding in anaesthetised sheep. In the present study, we have assessed the effect of cooling the right vagus after sectioning the left vagus (n = 6), and bilateral vagotomy (n = 7) on the bronchoconstrictor response to a single intravenous dose of substance P (SP) (0.3-1.0 mumol/kg) in anaesthetized female sheep aged 6 to 12 months. Respiratory parameters including tidal volume, flow and transpulmonary pressure pressure were measured, from which pulmonary resistance (RL; cmH2O.1(-1).s) and dynamic compliance (CDyn; ml.cmH2O(-1) were calculated. Systemic arterial pressures were also measured. Vagal cooling significantly attenuated the bronchoconstrictor response to SP at 7 degrees C (RL P < 0.01; Cdyn P < 0.001). A further reduction in the response to SP occurred at 3 degrees C, but this was not statistically significantly different from the response at 7 degrees C. Vagotomy abolished the response to SP. SP caused mild, but statistically insignificant, hypotension (119.7 vs. 107.7 mmHg). These results suggest SP causes bronchoconstriction in the anaesthetised sheep by vagal reflex mechanisms, involving stimulation of myelinated nerve fibre endings.

The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

PubMed

Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

2018-04-05

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

A novel surgical procedure of vagal nerve, lower esophageal sphincter, and pyloric sphincter-preserving nearly total gastrectomy reconstructed by single jejunal interposition, and postoperative quality of life.

PubMed

Tomita, Ryouichi

2005-01-01

For early gastric cancer total gastrectomy (TG) has so far been essentially unavoidable. We performed the nearly TG reconstructed by single jejunal interposition preservation of the vagal nerve, lower esophageal sphincter (LES) and pyloric sphincter (D1 or D2 lymph node dissection, curability A) as a function-preserving surgical technique (i.e. NTG) to improve postoperative quality of life (QOL). In this report, the application criteria and points of the technique are outlined. QOL in patients after NTG was also compared with those after TG. Sixteen subjects who underwent NTG (12 men and 4 women subjects at age 30 to 70 years, mean 55.6 years) were interviewed to inquire about abdominal symptoms and compared with 20 patients after conventional TG (excision with D2 lymph node, radical curability A) reconstructed by single jejunal interposition without preserving the vagal nerve, LES, and pyloric sphincter (i.e. TGI; 14 men and 6 women at age 26 to 70 years, mean 54.8 years). The former was named group A and the latter group B. Included were cases with early cancer localizing at the upper third and middle stomach, 2cm or further in distance from oral-side margin of the cancer to esophagogastric mucosal junction; and 3.5cm or further in distance from anal-side margin of the cancer to the pyloric sphincter. In excision with the lymph node, hepatic and celiac branches were preserved. To preserve LES, the abdominal esophagus was completely preserved. The pyloric antrum was also preserved at 1.5cm from the pyloric sphincter. The substitute stomach was created as a 30-cm-long single jejunal segment having orthodromic peristaltic movement. The operative procedure in group A significantly improved postoperative gastrointestinal symptoms such as appetite loss (p=0.0004), weight loss (p=0.0369), reflux esophagitis (RE) (p=0.0163), early dumping syndrome (p=0.0163), endoscopic RE (p=0.0311), and postgastrectomy cholecystolithiasis (p=0.0163) compared with group B. Oral intake

Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

ERIC Educational Resources Information Center

Miller, Jonas G.; Kahle, Sarah; Hastings, Paul D.

2017-01-01

Vagal tone is widely believed to be an important physiological aspect of emotion regulation and associated positive behaviors. However, there is inconsistent evidence for relations between children's baseline vagal tone and their helpful or prosocial responses to others (Hastings & Miller, 2014). Recent work in adults suggests a quadratic…

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

PubMed

Adrian, T E; Bloom, S R; Edwards, A V

1983-11-01

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species.

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

PubMed Central

Adrian, T E; Bloom, S R; Edwards, A V

1983-01-01

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species. PMID:6361233

Distribution of TRPV1- and TRPV2-immunoreactive afferent nerve endings in rat trachea.

PubMed

Yamamoto, Yoshio; Sato, Yoshikazu; Taniguchi, Kazuyuki

2007-12-01

Nociception in the trachea is important for respiratory modulation. We investigated the distribution, neurochemical characteristics, and origin of nerve endings with immunoreactivity for candidate sensor channels, TRPV1 and TRPV2, in rat trachea. In the epithelial layer, the intraepithelial nerve endings and dense subepithelial network of nerve fibers were immunoreactive for TRPV1. In contrast, TRPV2 immunoreactivity was observed mainly in nerve fibers of the tracheal submucosal layer and in several intrinsic ganglion cells in the peritracheal plexus. Double immunostaining revealed that some TRPV1-immunoreactive nerve fibers were also immunoreactive for substance P or calcitonin gene-related peptide, but neither neuropeptide colocalized with TRPV2. Injection of the retrograde tracer, fast blue, into the tracheal wall near the thoracic inlet demonstrated labeled neurons in the jugular, nodose, and dorsal root ganglia at segmental levels of C2-C8. In the jugular and nodose ganglia, 59.3% (70/118) and 10.7% (17/159), respectively, of fast blue-labeled neurons were immunoreactive for TRPV1, compared to 8.8% (8/91) and 2.6% (5/191) for TRPV2-immunoreactive. Our results indicate that TRPV1-immunoreactive nerve endings are important for tracheal nociception, and the different expression patterns of TRPV1 and TRPV2 with neuropeptides may reflect different subpopulations of sensory neurons.

ACTIVATION OF TRPA1 ON DURAL AFFERENTS: A POTENTIAL MECHANISM OF HEADACHE PAIN

PubMed Central

Edelmayer, Rebecca M.; Le, Larry N.; Yan, Jin; Wei, Xiaomei; Nassini, Romina; Materazzi, Serena; Preti, Delia; Appendino, Giovanni; Geppetti, Pierangelo; Dodick, David W.; Vanderah, Todd W.; Porreca, Frank; Dussor, Gregory

2012-01-01

Activation of transient receptor potential ankyrin-1 (TRPA1) on meningeal nerve endings has been suggested to contribute to environmental irritant-induced headache but this channel may also contribute to other forms of headache such as migraine. The preclinical studies described here examined functional expression of TRPA1 on dural afferents and investigated whether activation of TRPA1 contributes to headache-like behaviors. Whole-cell patch-clamp recordings were performed in vitro using two TRPA1 agonists, mustard oil (MO) and the environmental irritant umbellulone (UMB), on dural-projecting trigeminal ganglion neurons. Application of MO and UMB to dural afferents produced TRPA1-like currents in approximately 42% and 38% of cells, respectively. Using an established in vivo behavioral model of migraine-related allodynia, dural application of MO and UMB produced robust time-related tactile facial and hindpaw allodynia that was attenuated by pretreatment with the TRPA1 antagonist HC-030031. Additionally, MO or UMB were applied to the dura and exploratory activity was monitored for 30 minutes using an automated open-field activity chamber. Dural MO and UMB decreased the number of vertical rearing episodes and the time spent rearing in comparison to vehicle treated animals. This change in activity was prevented in rats pretreated with HC-030031 as well as sumatriptan, a clinically effective anti-migraine agent. These data indicate that TRPA1 is expressed on a substantial fraction of dural afferents and activation of meningeal TRPA1 produces behaviors consistent with those seen in patients during migraine attacks. Further, they suggest that activation of meningeal TRPA1 via endogenous or exogenous mechanisms can lead to afferent signaling and headache. PMID:22809691

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.

Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

PubMed Central

Browning, Kirsteen N.

2013-01-01

Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal (GI) functions. Glucose regulates GI functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells, and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in GI functions occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates GI functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research. PMID:24324393

Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation.

PubMed

Mandyam, Mala C; Vedantham, Vasanth; Scheinman, Melvin M; Tseng, Zian H; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Gerstenfeld, Edward P; Olgin, Jeffrey E; Marcus, Gregory M

2012-08-01

Alcohol and vagal activity may be important triggers for paroxysmal atrial fibrillation (PAF), but it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies. We compared self-reported frequency of these triggers in patients with PAF to those with other supraventricular tachycardias (SVTs). Consecutive consenting patients presenting for electrophysiology procedures at a single university medical center underwent a structured interview regarding arrhythmia triggers. Two hundred twenty-three patients with a documented arrhythmia (133 with PAF and 90 with SVT) completed the survey. After multivariable adjustment, patients with PAF had a 4.42 greater odds (95% confidence interval [CI] 1.35 to 14.44) of reporting alcohol consumption (p = 0.014) and a 2.02 greater odds (95% CI 1.02 to 4.00) of reporting vagal activity (p = 0.044) as an arrhythmia trigger compared to patients with SVT. In patients with PAF, drinking primarily beer was associated with alcohol as a trigger (odds ratio [OR] 4.49, 95% CI 1.41 to 14.28, p = 0.011), whereas younger age (OR 0.68, 95% CI 0.49 to 0.95, p = 0.022) and a family history of AF (OR 5.73, 95% CI 1.21 to 27.23, p = 0.028) each were independently associated with having vagal activity provoke an episode. Patients with PAF and alcohol triggers were more likely to have vagal triggers (OR 10.32, 95% CI 1.05 to 101.42, p = 0.045). In conclusion, alcohol consumption and vagal activity elicit PAF significantly more often than SVT. Alcohol and vagal triggers often were found in the same patients with PAF, raising the possibility that alcohol may precipitate AF by vagal mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Mechanism of Hyperphagia Contributing to Obesity in Brain-Derived Neurotrophic Factor Knockout Mice

PubMed Central

Fox, Edward A.; Biddinger, Jessica E.; Jones, Kevin R.; McAdams, Jennifer; Worman, Amber

2012-01-01

Global-heterozygous and brain-specific homozygous knockouts (KO's) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from gut-to-brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal vagal motor nucleus (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. PMID:23069761

Breathing exercises with vagal biofeedback may benefit patients with functional dyspepsia.

PubMed

Hjelland, Ina E; Svebak, Sven; Berstad, Arnold; Flatabø, Geir; Hausken, Trygve

2007-09-01

Many patients with functional dyspepsia (FD) have postprandial symptoms, impaired gastric accommodation and low vagal tone. The aim of this study was to improve vagal tone, and thereby also drinking capacity, intragastric volume and quality of life, using breathing exercises with vagal biofeedback. Forty FD patients were randomized to either a biofeedback group or a control group. The patients received similar information and care. Patients in the biofeedback group were trained in breathing exercises, 6 breaths/min, 5 min each day for 4 weeks, using specially designed software for vagal biofeedback. Effect variables included maximal drinking capacity using a drink test (Toro clear meat soup 100 ml/min), intragastric volume at maximal drinking capacity, respiratory sinus arrhythmia (RSA), skin conductance (SC) and dyspepsia-related quality of life scores. Drinking capacity and quality of life improved significantly more in the biofeedback group than in the control group (p=0.02 and p=0.01) without any significant change in baseline autonomic activity (RSA and SC) or intragastric volume. After the treatment period, RSA during breathing exercises was significantly correlated to drinking capacity (r=0.6, p=0.008). Breathing exercises with vagal biofeedback increased drinking capacity and improved quality of life in FD patients, but did not improve baseline vagal tone.

Infants' and Mothers' Vagal Reactivity in Response to Anger

ERIC Educational Resources Information Center

Moore, Ginger A.

2009-01-01

Background: Exposure to anger in the family is a risk factor for disruptive behavior disorders characterized by ineffective vagal regulation. Effects of anger on developing vagal regulation may be due to direct exposure or to effects on parents' regulation of emotion as parents support infants' regulation. Little is known about the impact of anger…

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

PubMed

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 ( n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 ( n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

PubMed Central

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

Ventricular tachyarrhythmia-related basal cardiomyopathy in rabbits with vagal stimulation--a novel experimental model for inverted Takotsubo-like cardiomyopathy.

PubMed

Takato, Tetsuya; Ashida, Terunao; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2010-07-01

Electrical stimulation of the intact (unsectioned) cervical vagus in rabbits frequently provokes ventricular tachyarrhythmias that are often accompanied by mitral regurgitation. Unique pathological lesions often arise on the mitral valve, papillary muscles, and mitral annulus (mitral complex), the latter two of which become swollen and stiffened. These lesions are reversible in nature. Previous studies have essentially ignored the basal portion except for the mitral annulus. Therefore, the present study examined pathological lesions on the left ventricular basal portion in rabbits. The intact right vagal nerves of 20 anesthetized rabbits were repeatedly electrically stimulated under electrocardiographic monitoring. Colloidal carbon (lml) was injected intravenously immediately after the end of the stimulation and all animals were killed 1 week later. Pathological lesions were identified as carbon deposits visible at gross examination. Ventricular bigeminy was induced after vagal stimulation in 15 (75%) of the 20 rabbits. Pathological lesions were evident on the basal portion in 16 (80%) and on the mitral valve and papillary muscles of 15 (75%) of the 20 rabbits. Ventricular bigeminy was closely associated with the development of the pathological lesions, which were rarely observed on the ventricular apex. Cardiomyopathic lesions involving the basal portion and mitral complex were frequently induced in rabbits by vagal stimulation. These lesions bear a close similarity in distribution and reversibility to inverted Takotsubo cardiomyopathy. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Recording nerve signals in canine sciatic nerves with a flexible penetrating microelectrode array

NASA Astrophysics Data System (ADS)

Byun, Donghak; Cho, Sung-Joon; Lee, Byeong Han; Min, Joongkee; Lee, Jong-Hyun; Kim, Sohee

2017-08-01

Objective. Previously, we presented the fabrication and characterization of a flexible penetrating microelectrode array (FPMA) as a neural interface device. In the present study, we aim to prove the feasibility of the developed FPMA as a chronic intrafascicular recording tool for peripheral applications. Approach. For recording from the peripheral nerves of medium-sized animals, the FPMA was integrated with an interconnection cable and other parts that were designed to fit canine sciatic nerves. The uniformity of tip exposure and in vitro electrochemical properties of the electrodes were characterized. The capability of the device to acquire in vivo electrophysiological signals was evaluated by implanting the FPMA assembly in canine sciatic nerves acutely as well as chronically for 4 weeks. We also examined the histology of implanted tissues to evaluate the damage caused by the device. Main results. Throughout recording sessions, we observed successful multi-channel recordings (up to 73% of viable electrode channels) of evoked afferent and spontaneous nerve unit spikes with high signal quality (SNR  >  4.9). Also, minor influences of the device implantation on the morphology of nerve tissues were found. Significance. The presented results demonstrate the viability of the developed FPMA device in the peripheral nerves of medium-sized animals, thereby bringing us a step closer to human applications. Furthermore, the obtained data provide a driving force toward a further study for device improvements to be used as a bidirectional neural interface in humans.

Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

NASA Astrophysics Data System (ADS)

Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

2014-06-01

Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

Similarities of the neuronal circuit for the induction of fictive vomiting between ferrets and dogs.

PubMed

Onishi, Takako; Mori, Takashi; Yanagihara, Mamoru; Furukawa, Naohiro; Fukuda, Hiroyuki

2007-10-30

Previous studies suggested that the following neuronal circuit participates in the induction of vomiting by afferent vagal stimulation in decerebrated paralyzed dogs: (1) afferent fibers of the vagus nerve, (2) neurons of the solitary nucleus (NTS), (3) neurons of the prodromal sign center near the semicompact part of the nucleus ambiguus (scAMB), (4) neurons of the central pattern generator in the reticular area adjacent to the compact part of nucleus ambiguus (cAMB), (5) respiratory premotor neurons in the caudal medulla, (6) motor neurons of the diaphragm and abdominal muscles. However, the commonality of this neuronal circuit in different species has not yet been clarified. Thus, this study was conducted to clarify this point. This study clarified for the first time that fictive vomiting in decerebrated paralyzed ferrets could be induced by vagal stimulation, and could be identified by centrifugal activity patterns of the phrenic and abdominal muscle nerves. The distributions of c-Fos immunoreactive neurons in the NTS, scAMB and cAMB areas in ferrets that exhibited fictive vomiting were denser than those in ferrets that did not. Application of the nonNMDA receptor antagonist into the 4th ventricle produced the reversible suppression of fictive vomiting. The NK1 receptor immunoreactive puncta were found in the reticular area adjacent to the scAMB. Microinjections of NK1 receptor antagonist into the reticular areas on both sides abolished fictive vomiting. All these results in the ferrets are identical with results previously obtained in dogs and cats. Therefore, this suggests that the above neuronal circuit commonly participates in the induction of emesis in these animal species.

High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

NASA Astrophysics Data System (ADS)

Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

2013-04-01

Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

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.

Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways

PubMed Central

Kaji, Izumi; Akiba, Yasutada; Kato, Ikuo; Maruta, Koji; Kuwahara, Atsukazu

2017-01-01

Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose dependently increased the rate of duodenal HCO3− secretion in perfused duodenal loops of anesthetized rats. Xenin was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the xenin/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of xenin-8 or xenin-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1, substance P (SP) receptor (NK1), or 5-hydroxytryptamine (5-HT)3, but not NTS2, inhibited the responses to xenin. Xenin-evoked Cl- secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodium channel Nav1.8 in combination with TTX, suggesting that peripheral xenin augments duodenal HCO3− and Cl− secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released xenin may account for its secretory effects in the duodenum. PMID:28115552

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.

CO2 stimulation of the cornea: a comparison between human sensation and nerve activity in polymodal nociceptive afferents of the cat.

PubMed

Chen, X; Gallar, J; Pozo, M A; Baeza, M; Belmonte, C

1995-06-01

Excitation of nociceptors by low pH has been proposed as a cause of pain following tissue injury. Here we have studied the effect of pH reductions caused by application of CO2 pulses to the cornea on the activity of corneal afferent nerves of the cat and on the magnitude of pain sensations in humans. Single-unit activity was recorded from corneal afferent fibres in anaesthetized cats. The corneal receptive field of A-delta or C polymodal nociceptive units was exposed for 30 s to a gas mixture with different concentrations of CO2 in air (0, 35, 50, 65, 80 and 98.5%). Responses to CO2 were evoked at a mean threshold concentration of 40 +/- 3% CO2. They consisted of a discharge of impulses that decayed gradually to a tonic level. In 15% of the units the initial burst was absent. The CO2 concentration and firing frequency data could be fitted to a power function with an exponent of 1.12. Pulses of CO2 were also applied to the cornea of 16 human volunteers. Sensations experienced were measured by means of a visual analogue scale and a verbal descriptor scale. Flow was adjusted below the mechanical stimulation threshold (2.8 +/- 0.5 mg). When mixtures containing 10-90% CO2 in 5% steps were applied as 3 s pulses, threshold sensation, described as a mild stinging pain, was evoked at 33.5 +/- 4.0% CO2. This sensation became overtly painful with higher CO2 concentrations (47.5 +/- 3.6% CO2). For the same subject the sensory threshold was remarkably constant, though it changed with longer exposure times. The relationship between CO2 concentration and magnitude of pain could be adjusted to a power function with a power exponent of 1.12. Curves of CO2 concentration versus neural discharges in the cat and versus psychophysical sensation in humans were very similar. These results show that corneal polymodal nociceptors respond to protons, and encode changes in CO2 concentration presumably reflecting pH changes. The same stimulus evokes corneal pain sensations in humans, thus

Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

NASA Technical Reports Server (NTRS)

Cochran, S. L.

1995-01-01

The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking.

PubMed

Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G; Farina, Dario; Sinkjær, Thomas; Mrachacz-Kersting, Natalie

2017-01-01

A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.

PubMed

Sarabia-Estrada, Rachel; Bañuelos-Pineda, Jacinto; Osuna Carrasco, Laura P; Jiménez-Vallejo, Salvador; Jiménez-Estrada, Ismael; Rivas-Celis, Efrain; Dueñas-Jiménez, Judith M; Dueñas-Jiménez, Sergio H

2015-07-01

Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes

Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in squirrel monkey vestibular nuclei. III. Correlation with vestibulospinal and vestibuloocular output pathways

NASA Technical Reports Server (NTRS)

Boyle, R.; Goldberg, J. M.; Highstein, S. M.

1992-01-01

1. A previous study measured the relative contributions made by regularly and irregularly discharging afferents to the monosynaptic vestibular nerve (Vi) input of individual secondary neurons located in and around the superior vestibular nucleus of barbiturate-anesthetized squirrel monkeys. Here, the analysis is extended to more caudal regions of the vestibular nuclei, which are a major source of both vestibuloocular and vestibulospinal pathways. As in the previous study, antidromic stimulation techniques are used to classify secondary neurons as oculomotor or spinal projecting. In addition, spinal-projecting neurons are distinguished by their descending pathways, their termination levels in the spinal cord, and their collateral projections to the IIIrd nucleus. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from secondary neurons as shocks of increasing strength were applied to Vi. Shocks were normalized in terms of the threshold (T) required to evoke field potentials in the vestibular nuclei. As shown previously, the relative contribution of irregular afferents to the total monosynaptic Vi input of each secondary neuron can be expressed as a %I index, the ratio (x100) of the relative sizes of the EPSPs evoked by shocks of 4 x T and 16 x T. 3. Antidromic stimulation was used to type secondary neurons as 1) medial vestibulospinal tract (MVST) cells projecting to spinal segments C1 or C6; 2) lateral vestibulospinal tract (LVST) cells projecting to C1, C6; or L1; 3) vestibulooculo-collic (VOC) cells projecting both to the IIIrd nucleus and by way of the MVST to C1 or C6; and 4) vestibuloocular (VOR) neurons projecting to the IIIrd nucleus but not to the spinal cord. Most of the neurons were located in the lateral vestibular nucleus (LV), including its dorsal (dLV) and ventral (vLV) divisions, and adjacent parts of the medial (MV) and descending nuclei (DV). Cells receiving quite different proportions of their direct inputs

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

PubMed Central

Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

1992-01-01

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

A Transactional Analysis of the Relation between Maternal Sensitivity and Child Vagal Regulation

ERIC Educational Resources Information Center

Perry, Nicole B.; Mackler, Jennifer S.; Calkins, Susan D.; Keane, Susan P.

2014-01-01

A transactional model examining the longitudinal association between vagal regulation (as indexed by vagal withdrawal) and maternal sensitivity from age 2.5 to age 5.5 was assessed. The sample included 356 children (171 male, 185 female) and their mothers who participated in a laboratory visit at age 2.5, 4.5, and 5.5. Cardiac vagal tone was…

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

PubMed

Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

1999-03-01

1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat

PubMed Central

Pettorossi, V E; Torre, G Della; Bortolami, R; Brunetti, O

1999-01-01

The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a ‘12-train’ series, an increasing inhibition. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots. PMID:10050025

Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

PubMed Central

Gladden, M H; Matsuzaki, H

2002-01-01

Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

PubMed

Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

2015-10-01

Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

Afferent Connectivity of the Zebrafish Habenulae

PubMed Central

Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

2016-01-01

The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

Phenotyping sensory nerve endings in vitro in the mouse

PubMed Central

Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W

2014-01-01

This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088

Histamine excites groups III and IV afferents from the cat knee joint depending on their resting activity.

PubMed

Herbert, M K; Just, H; Schmidt, R F

2001-06-08

The effect of histamine on the sensory activity of primary afferents was studied in normal and acutely inflamed cat knee joints. A subpopulation of groups III and IV articular afferents could be activated by close-arterial bolus injections of histamine: units with a high resting activity (about 100/min) were particular sensitive to histamine and were excited even by 3.3 fg histamine. The lower the resting discharges of groups III and IV units both from normal and acutely inflamed joints, the higher the dose of histamine (up to 3.3 or 33 microg) necessary to excite the nerve fibres. Thirty-seven of 39 units without any resting activity were completely insensitive to histamine. In contrast to its clear excitatory effect, histamine caused only minor changes in the responses to joint movements. Movement-evoked activity remained unchanged in 22 of 28 units, 1 unit was sensitized and 5 units showed reduced activity after histamine (3.3 microg). The present results support the notion that histamine may participate in the mediation of pain from injured or inflamed tissue. It is remarkable that histamine has a profound excitatory action on a proportion of both groups III and IV articular afferents without changing their sensitivity to joint movements.

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

KATP channels in the nodose ganglia mediate the orexigenic actions of ghrelin

PubMed Central

Grabauskas, Gintautas; Wu, Xiaoyin; Lu, Yuanxu; Heldsinger, Andrea; Song, Il; Zhou, Shi-Yi; Owyang, Chung

2015-01-01

Abstract Ghrelin is the only known hunger signal derived from the peripheral tissues. Ghrelin overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. The mechanisms by which ghrelin reduces the sensory signals evoked by anorexigenic hormones, which act via the vagus nerve to stimulate feeding, are unknown. Patch clamp recordings of isolated rat vagal neurons show that ghrelin hyperpolarizes neurons by activating K+ conductance. Administering a KATP channel antagonist or silencing Kir6.2, a major subunit of the KATP channel, abolished ghrelin inhibition in vitro and in vivo. Patch clamp studies show that ghrelin inhibits currents evoked by leptin and CCK-8, which operate through independent ionic channels. The inhibitory actions of ghrelin were abolished by treating the vagal ganglia neurons with pertussis toxin, as well as phosphatidylinositol 3-kinase (PI3K) or extracellular signal-regulated kinase 1 and 2 (Erk1/2) small interfering RNA. In vivo gene silencing of PI3K and Erk1/2 in the nodose ganglia prevented ghrelin inhibition of leptin- or CCK-8-evoked vagal firing. Feeding experiments showed that silencing Kir6.2 in the vagal ganglia abolished the orexigenic actions of ghrelin. These data indicate that ghrelin modulates vagal ganglia neuron excitability by activating KATP conductance via the growth hormone secretagogue receptor subtype 1a–Gαi–PI3K–Erk1/2–KATP pathway. The resulting hyperpolarization renders the neurons less responsive to signals evoked by anorexigenic hormones. This provides a mechanism to explain the actions of ghrelin with respect to overcoming anorexigenic signals that act via the vagal afferent pathways. Key points Ghrelin, a hunger signalling peptide derived from the peripheral tissues, overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. Using in vivo and in vitro electrophysiological

Device-based approaches for renal nerve ablation for hypertension and beyond.

PubMed

Thorp, Alicia A; Schlaich, Markus P

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

Device-based approaches for renal nerve ablation for hypertension and beyond

PubMed Central

Thorp, Alicia A.; Schlaich, Markus P.

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented. PMID:26217232

Longitudinal relations between child vagal tone and parenting behavior: 2 to 4 years.

PubMed

Kennedy, Amy E; Rubin, Kenneth H; Hastings, Paul D; Maisel, Beth

2004-07-01

The longitudinal relations between physiological markers of child emotion regulation and maternal parenting practices were examined from 2 to 4 years of age. At Time 1, cardiac vagal tone was assessed for one hundred four 2-year-olds (54 females); their mothers completed an assessment of parenting styles. Two years later, at Time 2, 84 of the original participants were reassessed on measures of cardiac vagal tone and parenting style. Results indicated both baseline cardiac vagal tone and maternal parenting practices to be stable from 2 to 4 years of age. Children's cardiac vagal tone predicted specific parenting practices from the toddler to preschool years. Further, child cardiac vagal tone moderated maternal restrictive-parenting practices from 2 to 4 years of age; mothers of children who were highly or moderately physiologically dysregulated were more likely to report restrictive parenting practices at both 2 and 4 years of age. Copyright 2004 Wiley Periodicals, Inc.

Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections.

PubMed

Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa; Bartel, Dianna L; Kaufman, Daniel; Girard, David; Whitehead, Mark C

2014-05-01

The nucleus of the solitary tract (NST) processes gustatory and related somatosensory information rostrally and general viscerosensory information caudally. To compare its connections with those of other rodents, this study in the C57BL/6J mouse provides a subnuclear cytoarchitectonic parcellation (Nissl stain) of the NST into rostral, intermediate, and caudal divisions. Subnuclei are further characterized by NADPH staining and P2X2 immunoreactivity (IR). Cholera toxin subunit B (CTb) labeling revealed those NST subnuclei receiving chorda tympani nerve (CT) afferents, those connecting with the parabrachial nucleus (PBN) and reticular formation (RF), and those interconnecting NST subnuclei. CT terminals are densest in the rostral central (RC) and medial (M) subnuclei; less dense in the rostral lateral (RL) subnucleus; and sparse in the ventral (V), ventral lateral (VL), and central lateral (CL) subnuclei. CTb injection into the PBN retrogradely labels cells in the aforementioned subnuclei; RC and M providing the largest source of PBN projection neurons. Pontine efferent axons terminate mainly in V and rostral medial (RM) subnuclei. CTb injection into the medullary RF labels cells and axonal endings predominantly in V at rostral and intermediate NST levels. Small CTb injections within the NST label extensive projections from the rostral division to caudal subnuclei. Projections from the caudal division primarily interconnect subnuclei confined to the caudal division of the NST; they also connect with the area postrema. P2X2 -IR identifies probable vagal nerve terminals in the central (Ce) subnucleus in the intermediate/caudal NST. Ce also shows intense NADPH staining and does not project to the PBN. Copyright © 2013 Wiley Periodicals, Inc.

Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections

PubMed Central

Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa; Bartel, Dianna L; Kaufman, Daniel; Girard, David; Whitehead, Mark C

2013-01-01

The nucleus of the solitary tract (NST) processes gustatory and related somatosensory information rostrally and general viscerosensory information caudally. To compare its connections with those of other rodents, this study in the C57BL/6J mouse provides a subnuclear cytoarchitectonic parcellation (Nissl stain) of the NST into rostral, intermediate, and caudal divisions. Subnuclei are further characterized by NADPH staining and P2X2 immunoreactivity (IR). Cholera toxin subunit B (CTb) labeling revealed those NST subnuclei receiving chorda tympani nerve (CT) afferents, those connecting with the parabrachial nucleus (PBN) and reticular formation (RF), and those interconnecting NST subnuclei. CT terminals are densest in the rostral central (RC) and medial (M) subnuclei; less dense in the rostral lateral (RL) subnucleus; and sparse in the ventral (V), ventral lateral (VL), and central lateral (CL) subnuclei. CTb injection into the PBN retrogradely labels cells in the aforementioned subnuclei; RC and M providing the largest source of PBN projection neurons. Pontine efferent axons terminate mainly in V and rostral medial (RM) subnuclei. CTb injection into the medullary RF labels cells and axonal endings predominantly in V at rostral and intermediate NST levels. Small CTb injections within the NST label extensive projections from the rostral division to caudal subnuclei. Projections from the caudal division primarily interconnect subnuclei confined to the caudal division of the NST; they also connect with the area postrema. P2X2-IR identifies probable vagal nerve terminals in the central (Ce) subnucleus in the intermediate/caudal NST. Ce also shows intense NADPH staining and does not project to the PBN. J. Comp. Neurol. 522:1565–1596, 2014. PMID:24151133

Lower Cardiac Vagal Tone in Non-Obese Healthy Men with Unfavorable Anthropometric Characteristics

PubMed Central

Ramos, Plínio S.; Araújo, Claudio Gil S.

2010-01-01

OBJECTIVES: to determine if there are differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics. INTRODUCTION: It is well established that obesity reduces cardiac vagal tone. However, it remains unknown if decreases in cardiac vagal tone can be observed early in non-obese healthy, adult men presenting unfavorable anthropometric characteristics. METHODS: Among 1688 individuals assessed between 2004 and 2008, we selected 118 non-obese (BMI <30 kg/m2), healthy men (no known disease conditions or regular use of relevant medications), aged between 20 and 77 years old (42 ± 12-years-old). Their evaluation included clinical examination, anthropometric assessment (body height and weight, sum of six skinfolds, waist circumference and somatotype), a 4-second exercise test to estimate cardiac vagal tone and a maximal cardiopulmonary exercise test to exclude individuals with myocardial ischemia. The same physician performed all procedures. RESULTS: A lower cardiac vagal tone was found for the individuals in the higher quintiles – unfavorable anthropometric characteristics - of BMI (p=0.005), sum of six skinfolds (p=0.037) and waist circumference (p<0.001). In addition, the more endomorphic individuals also presented a lower cardiac vagal tone (p=0.023), while an ectomorphic build was related to higher cardiac vagal tone values as estimated by the 4-second exercise test (r=0.23; p=0.017). CONCLUSIONS: Non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. Early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease. PMID:20126345

[Acute pancreatitis and afferent loop syndrome. Case report].

PubMed

Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

2013-01-01

The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

PubMed Central

Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

2010-01-01

The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

Endoscopic Endonasal Optic Nerve Decompression for Fibrous Dysplasia

PubMed Central

DeKlotz, Timothy R.; Stefko, S. Tonya; Fernandez-Miranda, Juan C.; Gardner, Paul A.; Snyderman, Carl H.; Wang, Eric W.

2016-01-01

Objective To evaluate visual outcomes and potential complications for optic nerve decompression using an endoscopic endonasal approach (EEA) for fibrous dysplasia. Design Retrospective chart review of patients with fibrous dysplasia causing extrinsic compression of the canalicular segment of the optic nerve that underwent an endoscopic endonasal optic nerve decompression at the University of Pittsburgh Medical Center from 2010 to 2013. Main Outcome Measures The primary outcome measure assessed was best-corrected visual acuity (BCVA) with secondary outcomes, including visual field testing, color vision, and complications associated with the intervention. Results A total of four patients and five optic nerves were decompressed via an EEA. All patients were symptomatic preoperatively and had objective findings compatible with compressive optic neuropathy: decreased visual acuity was noted preoperatively in three patients while the remaining patient demonstrated an afferent pupillary defect. BCVA improved in all patients postoperatively. No major complications were identified. Conclusion EEA for optic nerve decompression appears to be a safe and effective treatment for patients with compressive optic neuropathy secondary to fibrous dysplasia. Further studies are required to identify selection criteria for an open versus an endoscopic approach. PMID:28180039

Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report.

PubMed

De Ridder, Dirk; Kilgard, Michael; Engineer, Navzer; Vanneste, Sven

2015-04-01

Classical neuromodulation consists of applying electrical or magnetic stimuli to the nervous system to modulate ongoing activity and connectivity. However, recently, an exciting novel neuromodulation technique was developed in which stimulation of the vagal nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats. To determine whether this therapy could also be effective in humans, we delivered a similar therapy in a patient with chronic tinnitus unresponsive to previous therapies. In this report, we describe the case of a 59-year-old man who suffered from bilateral tinnitus for 14 years that arose after a cervical fusion operation. Pharmacotherapy, transcranial magnetic stimulation, transcranial direct current stimulation, neurofeedback, and bilateral auditory cortex stimulation via implanted electrodes did not improve the tinnitus. After implanting the vagal nerve stimulator, the patient received daily vagus nerve stimulation tone pairings for 4 weeks in a non-placebo-controlled way. At the end of therapy, the patient experienced a significant reduction in tinnitus symptoms that lasted for 2 months after treatment. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire were reduced by 48% and 68%, respectively. Symptoms of depression were also improved by 40%, as quantified by the Beck Depression Inventory. Three months after ending therapy, placebo stimulation was performed consisting of only tone presentation without the simultaneous electrical stimuli. This resulted in further continuation of the gradual relapse to the baseline state, without renewed improvement. Our results suggest that vagus nerve stimulation paired with tones could become an effective therapy for the treatment of tinnitus.

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.

Correlation between afferent rearrangements and behavioral deficits after local excitotoxic insult in the mammalian vestibule: a rat model of vertigo symptoms.

PubMed

Gaboyard-Niay, Sophie; Travo, Cécile; Saleur, Aurélie; Broussy, Audrey; Brugeaud, Aurore; Chabbert, Christian

2016-10-01

Damage to inner ear afferent terminals is believed to result in many auditory and vestibular dysfunctions. The sequence of afferent injuries and repair, as well as their correlation with vertigo symptoms, remains poorly documented. In particular, information on the changes that take place at the primary vestibular endings during the first hours following a selective insult is lacking. In the present study, we combined histological analysis with behavioral assessments of vestibular function in a rat model of unilateral vestibular excitotoxic insult. Excitotoxicity resulted in an immediate but transient alteration of the balance function that was resolved within a week. Concomitantly, vestibular primary afferents underwent a sequence of structural changes followed by spontaneous repair. Within the first two hours after the insult, a first phase of pronounced vestibular dysfunction coincided with extensive swelling of afferent terminals. In the next 24 h, a second phase of significant but incomplete reduction of the vestibular dysfunction was accompanied by a resorption of swollen terminals and fiber retraction. Eventually, within 1 week, a third phase of complete balance restoration occurred. The slow and progressive withdrawal of the balance dysfunction correlated with full reconstitution of nerve terminals. Competitive re-innervation by afferent and efferent terminals that mimicked developmental synaptogenesis resulted in full re-afferentation of the sensory epithelia. By deciphering the sequence of structural alterations that occur in the vestibule during selective excitotoxic impairment, this study offers new understanding of how a vestibular insult develops in the vestibule and how it governs the heterogeneity of vertigo symptoms. © 2016. Published by The Company of Biologists Ltd.

The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

PubMed

Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

2015-04-20

What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.

PubMed

Aizawa, Naoki; Wakamatsu, Daisuke; Kida, Jun; Otsuki, Takeya; Saito, Yasuho; Matsuya, Hidekazu; Homma, Yukio; Igawa, Yasuhiko

2017-02-01

Kv7 voltage-gated potassium channels have been suggested to modulate mechano-afferent transduction and nociception in the bladder. We investigated the effects of retigabine, a Kv7 channel activator, on rhythmic bladder contractions (RBCs), and single-unit afferent activities (SAAs) of the primary bladder mechanosensitive afferent nerve fibers in urethane-anesthetized rats. In addition, the effects of pretreatment with retigabine on the nociceptive behaviors provoked by an intravesical instillation of resiniferatoxin (RTX) were evaluated in the conscious condition. Female Sprague-Dawley rats were used. Under urethane anesthesia, saline was instilled into the bladder until RBCs were induced reproducibly. Then, the effects of intravenous, cumulative administrations of retigabine (0.1-3 mg/kg) or vehicle (saline) on RBCs were assessed. In separate animals, SAAs of Aδ- and C-fibers were identified by electrical stimulation of the pelvic nerve and by bladder distention with saline. After baseline recording, vehicle or retigabine (0.01-1 mg/kg) was administered intravenously and further recordings were performed. Under pretreatment with vehicle or retigabine (3 mg/kg intraperitoneally), the frequencies of lower abdominal licking and freezing were counted and scored as the bladder nociceptive behaviors induced by intravesical RTX instillation (3 µM, 0.3 ml). Retigabine dose-dependently decreased both the frequency and the amplitude of RBCs and SAAs of both Aδ- and C-fibers. The effect on RBCs was more potent on the frequency than the amplitude. Retigabine inhibited the RTX-induced abdominal licking, but not freezing. Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

PubMed Central

Grey, Michael J; Ladouceur, Michel; Andersen, Jacob B; Nielsen, Jens Bo; Sinkjær, Thomas

2001-01-01

The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h−1 with the left ankle attached to a portable stretching device. The soleus stretch reflex was elicited by applying small amplitude (∼8 deg) dorsiflexion perturbations 200 ms after heel contact. Short and medium latency responses were observed with latencies of 55 ± 5 and 78 ± 6 ms, respectively. The short latency response was velocity sensitive (P < 0.001), while the medium latency response was not (P = 0.725). Nerve cooling increased the delay of the medium latency component to a greater extent than that of the short latency component (P < 0.005). Ischaemia strongly decreased the short latency component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). Two hours after the ingestion of tizanidine, an α2-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P = 0.007), whereas the short latency component was unchanged (P = 0.653). An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. Our results support the hypothesis that, during walking the medium latency component of the stretch reflex resulting from an unexpected perturbation is contributed to by group II muscle afferents. PMID:11483721

Vestibular afferent responses to linear accelerations in the alert squirrel monkey

NASA Technical Reports Server (NTRS)

Somps, Christopher J.; Schor, Robert H.; Tomko, David L.

1994-01-01

The spontaneous activity of 40 otolith afferents and 44 canal afferents was recorded in 4 alert, intact squirrel monkeys. Polarization vectors and response properties of otolith afferents were determined during static re-orientations relative to gravity and during Earth-horizontal, sinusoidal, linear oscillations. Canal afferents were tested for sensitivity to linear accelerations. For regular otolith afferents, a significant correlation between upright discharge rate and sensitivity to dynamic acceleration in the horizontal plane was observed. This correlation was not present in irregular units. The sensitivity of otolith afferents to both static tilts and dynamic linear acceleration was much greater in irregularly discharging units than in regularly discharging units. The spontaneous activity and static and dynamic response properties of regularly discharging otolith afferents were similar to those reported in barbiturate-anesthetized squirrel monkeys. Irregular afferents also had similar dynamic response properties when compared to anesthetized monkeys. However, this sample of irregular afferents in alert animals had higher resting discharge rates and greater sensitivity to static tilts. The majority of otolith polarization vectors were oriented near the horizontal in the plane of the utricular maculae; however, directions of maximum sensitivity were different during dynamic and static testing. Canal afferents were not sensitive to static tilts or linear oscillations of the head.

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.

The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

PubMed

Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

2018-01-03

Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p < 0.05), and delayed the time to VF after coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p < 0.05). In Group 2, vagal stimulation did not modify the time to VF (103 ± 39 vs. 91 ± 20 s). Analyses revealed that heart rate and the time to VF were positively linearly related. Maintaining a constant heart rate with atrial electrical stimulation in pigs prevented vagal stimulation from modifying the time to VF after acute coronary occlusion.

Voluntary control of breathing does not alter vagal modulation of heart rate

NASA Technical Reports Server (NTRS)

Patwardhan, A. R.; Evans, J. M.; Bruce, E. N.; Eckberg, D. L.; Knapp, C. F.

1995-01-01

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients

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

Higenbottam, T.; Jackson, M.; Woolman, P.

1989-07-01

As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilledmore » distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.« less

BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

PubMed Central

Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

2016-01-01

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

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

Parental Socialization, Vagal Regulation, and Preschoolers' Anxious Difficulties: Direct Mothers and Moderated Fathers

ERIC Educational Resources Information Center

Hastings, Paul D.; Sullivan, Caroline; McShane, Kelly E.; Coplan, Robert J.; Utendale, William T.; Vyncke, Johanna D.

2008-01-01

Parental supportiveness and protective overcontrol and preschoolers' parasympathetic regulation were examined as predictors of temperamental inhibition, social wariness, and internalizing problems. Lower baseline vagal tone and weaker vagal suppression were expected to mark poorer dispositional self-regulatory capacity, leaving children more…

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

PubMed

Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

2016-07-01

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. Copyright © 2016 the American Physiological Society.

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

PubMed Central

Xing, Jihong; Li, Jianhua

2017-01-01

Background/Aims Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex. Methods A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues were obtained to examine the protein levels of PAR2 using western blot analysis. Current responses induced by activation of TRPA1 in skeletal muscle DRG neurons were characterized using whole-cell patch clamp methods. The blood pressure response to static exercise (i.e., muscle contraction) and stimulation of TRPA1 was also examined after a blockade of PAR2. Results The expression of PAR2 was amplified in DRG neurons of the occluded limb, and PAR2 activation with SL-NH2 (a PAR2 agonist) increased the amplitude of TRPA1 currents to a greater degree in DRG neurons of the occluded limb. Moreover, FSLLRY-NH2 (a PAR antagonist) injected into the arterial blood supply of the hindlimb muscles significantly attenuated the pressor response to muscle contraction and TRPA1 stimulation in rats with occluded limbs. Conclusions The PAR2 signal in muscle sensory nerves contributes to the amplified exercise pressor reflex via TRPA1 mechanisms in rats with femoral artery ligation. These findings provide a pathophysiological basis for autonomic responses during exercise activity in PAD, which may potentially aid in the development of therapeutic approaches for improvement of blood flow in this disease. PMID:29131007

Vagal and sympathetic activity in burnouts during a mentally demanding workday.

PubMed

Zanstra, Ydwine J; Schellekens, Jan M H; Schaap, Cas; Kooistra, Libbe

2006-01-01

We study differences in task performance and related sympathetic-vagal reaction patterns between burnouts and controls during a mentally demanding workday. Thirty-nine adults with burnout and 40 healthy controls performed mental tasks during a simulated workday. At pretest, just before lunch (lunch test) and at the end of the day (posttest), a Stroop color word task was administered as a probe task. Efficiency (the relation between performance and effort during the probe task), performance (reaction time and errors), and effort (self-report) were measured, as well as cardiovascular indices of sympathetic (blood pressure) and vagal (respiratory sinus arrhythmia) activity. Performance and effort investment of both burnouts and controls did not differ during pretest. As the day progressed the performance of controls improved more than the performance of burnouts. Moreover, the control group showed a decrease of blood pressure in response to mental task demands, a decrease in respiratory sinus arrhythmia activity, and no change in experienced effort. In the burnout group, no change could be demonstrated in blood pressure, suggesting a sympathetic predominance in the sympathetic-vagal balance. Burnouts experienced an increase in effort and were more tired at the end of the workday. Burnouts and healthy controls differ in their pattern of sympathetic-vagal activity only after long-lasting work demands. Findings give limited support to Porges's view that in healthy subjects, the vagal system is more responsive to challenging task situations than in chronically stressed individuals. The distinction between two phases in the burnout on the basis of behavioral and physiological characteristics is discussed.

Reduced cardiac vagal activity in obese children and adolescents.

PubMed

Dangardt, Frida; Volkmann, Reinhard; Chen, Yun; Osika, Walter; Mårild, Staffan; Friberg, Peter

2011-03-01

  Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals.   Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16±7 versus 21±9 (P<0·01) and 22±10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status.   Children with obesity had low vagal activity at rest, and there was no gender difference. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Bronchoconstriction induced by hyperventilation with humidified hot air: role of TRPV1-expressing airway afferents.

PubMed

Lin, Ruei-Lung; Hayes, Don; Lee, Lu-Yuan

2009-06-01

A recent study by our laboratory has shown that an increase in intrathoracic temperature activates vagal pulmonary C-fibers. Because these afferents are known to elicit reflex bronchoconstriction upon stimulation, this study was carried out to investigate if an increase in airway temperature within the physiological range alters bronchomotor tone. Adult guinea pigs were anesthetized and mechanically ventilated via a tracheal tube. After the lung had been hyperventilated with humidified hot air (HHA) for 4 min, the tracheal temperature was elevated from 36.4 to 40.5 degrees C, which induced an immediate bronchoconstriction, increasing total pulmonary resistance (R(L)) to 177 +/- 10% and decreasing dynamic lung compliance to 81 +/- 6% of their respective baselines. The increase in R(L) returned spontaneously toward the baseline in <10 min and was reproducible in the same animals. There were no difference in the responses whether the humidity was generated from distilled water or isotonic saline. In contrast, hyperventilation with humidified air at room temperature did not cause any increase in R(L). The increase in R(L) caused by HHA was attenuated by 65.9% after a pretreatment with atropine alone and by 72.0% after a pretreatment with a combination of atropine and neurokinin receptor type 1 and 2 antagonists. In addition, capsazepine, a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, reduced the HHA-induced increase in R(L) by 64.1% but did not abolish it. However, pretreatment with formoterol, a beta(2)-agonist, completely prevented the HHA-induced bronchoconstriction. These results indicate that the increase in airway temperature induced transient airway constriction in guinea pigs. Approximately two-thirds of the increase in bronchomotor tone was mediated through the cholinergic reflex, which was probably elicited by the activation of TRPV1-expressing airway afferents. The remaining bronchoconstriction was caused by other, yet

Somatotopic organization of primary afferent perikarya of the guinea-pig extraocular muscles in the trigeminal ganglion: a post-mortem DiI-tracing study.

PubMed

Aigner, M; Robert Lukas, J; Denk, M; Ziya-Ghazvini, F; Kaider, A; Mayr, R

2000-04-01

Apart from the somatotopic organization of the trigeminal ganglion (TG) into the ophthalmic, maxillary and mandibular divisions along the mediolateral axis, there exist further somatotopic organizations within these three divisions. According to literature, the cell organization in the TG and the somatotopy in the brainstem develop together, formed by naturally occurring cell death in the TG. Thus, the somatotopy of the primary afferent trigeminal perikarya is of special interest. The aim of this study was to investigate the location of the primary afferent perikarya of the extraocular muscles (EOMs) in the TG of guinea-pig. The primary afferent perikarya were labeled by post-mortem application of the carbocyanine DiI on the oculomotor nerve branches near their entrance into the single EOMs. The DiI-positive perikarya were found musculo-somatically organized in the ipsilateral ophthalmic part of the TG at a wide range along the dorsoventral axis, expressing an overlap of the representation areas. The primary afferent perikarya of the superior rectus and the superior oblique muscles were mainly localized in the dorsal part of the ganglion while those of the inferior rectus and the inferior oblique muscle mainly in ventral part. The lateral and the medial rectus were predominantly represented in between. An organization along the mediolateral axis of the TG was not observed. Although guinea-pigs lack classical EOM proprioceptors, the somatotopic representation of the extraocular muscle primary afferent perikarya in the TG found in this study is in line with findings in species with well known encapsulated proprioceptors within the EOMs.

The gustatory system of lampreys.

PubMed

Barreiro-Iglesias, Antón; Anadón, Ramón; Rodicio, María Celina

2010-01-01

The present is a review of the gustatory system of lampreys, which are representative of the earliest vertebrates. They are the oldest extant vertebrates that possess taste buds. Because of the phylogenetic position of lampreys, the study of their gustatory system will provide important information to help understand the early evolution of this system in vertebrates. The taste buds of larval lampreys, which are papillae located on the first six pairs of gill arches facing the water current, respond to classical taste substances. They consist of two types of tall differentiated cells, serotonergic biciliated taste receptors ('light' cells) and microvillous sustentacular cells ('dark cells'). The taste buds also contain basal proliferative cells. Afferent gustatory fibers of the glossopharyngeal and vagal nerves innervate the taste buds of lampreys and contact the basal surface of the biciliated cells without entering the bud. Central processes of the glossopharyngeal and vagal cranial nerves terminate in a caudal rhombencephalic region that may correspond to the nucleus of the solitary tract of gnathostomes. To date, most studies in lampreys have focused on characterizing taste buds; future research should focus on the central processing of the gustatory information. Here we will review the current knowledge about the gustatory system of lampreys to provide a basis for establishing the direction of further studies of this chemosensory system. Copyright 2010 S. Karger AG, Basel.

Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

PubMed

Zielinski, Mark R; Dunbrasky, Danielle L; Taishi, Ping; Souza, Gianne; Krueger, James M

2013-08-01

Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.

Cardiac vagal flexibility and accurate personality impressions: Examining a physiological correlate of the good judge.

PubMed

Human, Lauren J; Mendes, Wendy Berry

2018-02-23

Research has long sought to identify which individuals are best at accurately perceiving others' personalities or are good judges, yet consistent predictors of this ability have been difficult to find. In the current studies, we revisit this question by examining a novel physiological correlate of social sensitivity, cardiac vagal flexibility, which reflects dynamic modulation of cardiac vagal control. We examined whether greater cardiac vagal flexibility was associated with forming more accurate personality impressions, defined as viewing targets more in line with their distinctive self-reported profile of traits, in two studies, including a thin-slice video perceptions study (N = 109) and a dyadic interaction study (N = 175). Across studies, we found that individuals higher in vagal flexibility formed significantly more accurate first impressions of others' more observable personality traits (e.g., extraversion, creativity, warmth). These associations held while including a range of relevant covariates, including cardiac vagal tone, sympathetic activation, and gender. In sum, social sensitivity as indexed by cardiac vagal flexibility is linked to forming more accurate impressions of others' observable traits, shedding light on a characteristic that may help to identify the elusive good judge and providing insight into its neurobiological underpinnings. © 2018 Wiley Periodicals, Inc.

VERSATILE, HIGH-RESOLUTION ANTEROGRADE LABELING OF VAGAL EFFERENT PROJECTIONS WITH DEXTRAN AMINES

PubMed Central

Walter, Gary C.; Phillips, Robert J.; Baronowsky, Elizabeth A.; Powley, Terry L.

2009-01-01

None of the anterograde tracers used to label and investigate vagal preganglionic neurons projecting to the viscera has proved optimal for routine and extensive labeling of autonomic terminal fields. To identify an alternative tracer protocol, the present experiment evaluated whether dextran conjugates, which have produced superior results in the CNS, might yield widespread and effective labeling of long, fine-caliber vagal efferents in the peripheral nervous system. The dextran conjugates that were evaluated proved reliable and versatile for labeling the motor neuron pool in its entirety, for single- and multiple-labeling protocols, for both conventional and confocal fluorescence microscopy, and for permanent labeling protocols for brightfield microscopy of the projections to the gastrointestinal (GI) tract. Using a standard ABC kit followed by visualization with DAB as the chromagen, Golgi-like labeling of the vagal efferent terminal fields in the GI wall was achieved with the biotinylated dextrans. The definition of individual terminal varicosities was so sharp and detailed that it was routinely practical to examine the relationship of putative vagal efferent contacts (by the criteria of high magnification light microscopy) with the dendritic and somatic architecture of counterstained neurons in the myenteric plexus. Overall, dextran conjugates provide high-definition labeling of an extensive vagal motor pool in the GI tract, and offer considerable versatility when multiple-staining protocols are needed to elucidate the complexities of the innervation of the gut. PMID:19056424

Patterning of sympathetic nerve activity in response to vestibular stimulation

NASA Technical Reports Server (NTRS)

Kerman, I. A.; McAllen, R. M.; Yates, B. J.

2000-01-01

Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

Carotid Space Mass Proximal to Vagus Nerve Causing Asystole and Syncope.

PubMed

Leviter, Julie; Wiznia, Daniel H

2016-01-01

Manipulation of vagal nerve rootlets, whether surgical or through mass effect of a neoplasm, can result in asystole and hypotension, accompanied by ST depression and right bundle branch block. There are few case reports of a neoplasm causing these effects, and this case describes a patient with such a mass presenting with syncopal episodes. A 43-year-old man with a past medical history of HIV, bipolar disorder, and epilepsy was admitted to the neurology service for a video electroencephalogram (vEEG) to characterize syncopal episodes that were felt to be epileptic in origin. During the study, he experienced symptoms of his typical aura, which correlated with a transient symptomatic high degree AV block on telemetry, and an absence of epileptic findings on vEEG. Magnetic Resonance Imaging (MRI) of the brain showed a mass in the left posterior carotid space at the skull base. The patient underwent permanent dual chamber MRI-compatible pacemaker placement for his heart block. His syncopal episodes resolved, but presyncopal symptoms persisted. We discuss the presentation and treatment of vagal neoplasms.

Presynaptic Inhibition of Diverse Afferents to the Locus Coeruleus by Kappa Opiate Receptors: a Novel Mechanism for Regulating the Central Norepinephrine System

PubMed Central

Kreibich, Arati S.; Reyes, Beverly A. S.; Curtis, Andre L.; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J.; Valentino, Rita J.

2008-01-01

The norepinephrine nucleus, locus coeruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAA), corticotropin-releasing factor (CRF) and endogenous opioids acting at μ-opiate receptors. As the LC is also innervated by the endogenous κ-opiate receptor (κ-OR) ligand, dynorphin, and expresses κ-ORs, this study investigated κ-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of κ-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the κ-OR agonist, U50488, into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the κ-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that κ-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-NE system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate κ-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders or disorders characterized by abnormal sensory responses, such as autism. PMID:18562623

Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

PubMed

Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

2008-06-18

The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit

NASA Technical Reports Server (NTRS)

Torigoe, Yasuhiro; Cernucan, Roxana D.; Nishimoto, Jo Ann S.; Blanks, Robert H. I.

1985-01-01

As a part of the study of the vestibular-autonomic pathways involved in motion sickness, the location and the morphology of preganglionic sympathetic neurons (PSNs) projecting via the greater splanchnic nerve were examined. Retrograde labeling of neurons was obtained by application of horseradish peroxidase to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column, but a significant portion also occurred within the lateral funiculus, the intercalated region, and the central autonomic area; the proportion of labeling between the four regions depended on the spinal cord segment.

The contribution of coping related variables and cardiac vagal activity on the performance of a dart throwing task under pressure.

PubMed

Mosley, Emma; Laborde, Sylvain; Kavanagh, Emma

2017-10-01

The aims of this study were 1) to assess the predictive role of coping related variables (CRV) on cardiac vagal activity (derived from heart rate variability), and 2) to investigate the influence of CRV (including cardiac vagal activity) on a dart throwing task under low pressure (LP) and high pressure (HP) conditions. Participants (n=51) completed trait CRV questionnaires: Decision Specific Reinvestment Scale, Movement Specific Reinvestment Scale and Trait Emotional Intelligence Questionnaire. They competed in a dart throwing task under LP and HP conditions. Cardiac vagal activity measurements were taken at resting, task and during recovery for 5min. Self-reported ratings of stress were recorded at three time points via a visual analogue scale. Upon completion of the task, self-report measures of motivation, stress appraisal, attention, perceived pressure and dart throwing experience were completed. Results indicated that resting cardiac vagal activity had no predictors. Task cardiac vagal activity was predicted by resting cardiac vagal activity in both pressure conditions with the addition of a trait CRV in HP. Post task cardiac vagal activity was predicted by resting cardiac vagal activity in both conditions with the addition of a trait CRV in HP. Cardiac vagal reactivity (difference from resting to task) was predicted by a trait CRV in HP conditions. Cardiac vagal recovery (difference from task to post task) was predicted by a state CRV only in LP. Dart throwing task performance was predicted by a combination of both CRV and cardiac vagal activity. The current research suggests that coping related variables and cardiac vagal activity influence dart throwing task performance differently dependent on pressure condition. Copyright © 2017 Elsevier Inc. All rights reserved.

The correlated blanching of synaptic bodies and reduction in afferent firing rates caused by transmitter-depleting agents in the frog semicircular canal

NASA Technical Reports Server (NTRS)

Guth, P.; Norris, C.; Fermin, C. D.; Pantoja, M.

1993-01-01

Synaptic bodies (SBs) associated with rings of synaptic vesicles and well-defined, pre- and post-synaptic membrane structures are indicators of maturity in most hair cell-afferent nerve junctions. The role of the SBs remains elusive despite several experiments showing that they may be involved in storage of neurotransmitter. Our results demonstrate that SBs of the adult posterior semicircular canal (SCC) cristae hair cells become less electron dense following incubation of the SCC with the transmitter-depleting drug tetrabenazine (TBZ). Objective quantification and comparison of the densities of the SBs in untreated and TBZ-treated frog SCC demonstrated that TBZ significantly decreased the electron density of SBs. This reduction in electron density was accompanied by a reduction in firing rates of afferent fibers innervating the posterior SCC. A second transmitter-depleting drug, guanethidine, previously shown to reduce the electron density of hair cell SBs, also reduced the firing rates of afferent fibers innervating the posterior SCC. In contrast, the electron density of dense granules (DG), similar in size and shape to synaptic bodies (SB) in hair cells, did not change after incubation in TBZ, thus indicating that granules and SBs are not similar in regard to their electron density. The role of SBs in synaptic transmission and the transmitter, if any, stored in the SBs remain unknown. Nonetheless, the association of the lessening of electron density with a reduction in afferent firing rate provides impetus for the further investigation of the SB's role in neurotransmission.

The vagus and recurrent laryngeal nerves in the rodent experimental model of esophageal atresia.

PubMed

Qi, B Q; Merei, J; Farmer, P; Hasthorpe, S; Myers, N A; Beasley, S W; Hutson, J M

1997-11-01

After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.

Edge orientation signals in tactile afferents of macaques

PubMed Central

Suresh, Aneesha K.

2016-01-01

The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic. PMID:27655968

Too much of a good thing? Cardiac vagal tone's nonlinear relationship with well-being.

PubMed

Kogan, Aleksandr; Gruber, June; Shallcross, Amanda J; Ford, Brett Q; Mauss, Iris B

2013-08-01

Parasympathetic regulation of heart rate through the vagus nerve--often measured as resting respiratory sinus arrhythmia or cardiac vagal tone (CVT)--is a key biological correlate of psychological well-being. However, recent theorizing has suggested that many biological and psychological processes can become maladaptive when they reach extreme levels. This raises the possibility that CVT might not have an unmitigated positive relationship with well-being. In line with this reasoning, across 231 adult participants (Mage = 40.02 years; 52% female), we found that CVT was quadratically related to multiple measures of well-being, including life satisfaction and depressive symptoms. Individuals with moderate CVT had higher well-being than those with low or high CVT. These results provide the first direct evidence of a nonlinear relationship between CVT and well-being, adding to a growing body of research that has suggested some biological processes may cease being adaptive when they reach extreme levels. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Trigemino-gustatory interactions: a randomized controlled clinical trial assessing the effects of selective anesthesia of dental afferents on taste thresholds.

PubMed

Lecor, Papa Abdou; Touré, Babacar; Boucher, Yves

2018-03-01

This study aimed at analyzing the effect of the temporary removal of trigeminal dental afferents on electrogustometric thresholds (EGMt). EGMt were measured in 300 healthy subjects randomized in three groups, in nine loci on the right and left side (RS, LS) of the tongue surface before and after anesthesia. Group IAN (n = 56 RS, n = 44 LS) received intraosseous local anesthesia of the inferior alveolar nerve (IAN). Group MdN received mandibular nerve (MdN) block targeting IAN before its entrance into the mandibular foramen (n = 60, RS, and n = 40, LS); group MxN receiving maxillary nerve (MxN) anesthesia (n = 56 RS and n = 44 LS) was the control group. Differences between mean EGMt were analyzed with the Wilcoxon test; correlation between type of anesthesia and EGMt was performed with Spearman's rho, all with a level of significance set at p ≤ 0.05. Significant EGMt (μA) differences before and after anesthesia were found in all loci with MdN and IAN on the ipsilateral side (p < 0.05), but not with MxN. Anesthesia of the MdN was positively correlated with the increase in EGMt (p < 0.001). Selective anesthesia of IAN was positively correlated only with the increase in EGMt measured at posterior and dorsal loci of the tongue surface (p < 0.01). The increase in EGMt following IAN anesthesia suggests a participation of dental afferents in taste perception. Extraction of teeth may impair food intake not only due to impaired masticatory ability but also to alteration of neurological trigemino-gustatory interactions. PACTR201602001452260.

Vagus nerve contributes to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice.

PubMed

Gao, Xia; van der Veen, Jelske N; Zhu, Linfu; Chaba, Todd; Ordoñez, Marta; Lingrell, Susanne; Koonen, Debby P Y; Dyck, Jason R B; Gomez-Muñoz, Antonio; Vance, Dennis E; Jacobs, René L

2015-04-01

Phosphatidylethanolamine N-methyltransferase (PEMT), a liver enriched enzyme, is responsible for approximately one third of hepatic phosphatidylcholine biosynthesis. When fed a high-fat diet (HFD), Pemt(-/-) mice are protected from HF-induced obesity; however, they develop steatohepatitis. The vagus nerve relays signals between liver and brain that regulate peripheral adiposity and pancreas function. Here we explore a possible role of the hepatic branch of the vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice. 8-week old Pemt(-/-) and Pemt(+/+) mice were subjected to hepatic vagotomy (HV) or capsaicin treatment, which selectively disrupts afferent nerves, and were compared to sham-operated or vehicle-treatment, respectively. After surgery, mice were fed a HFD for 10 weeks. HV abolished the protection against the HFD-induced obesity and glucose intolerance in Pemt(-/-) mice. HV normalized phospholipid content and prevented steatohepatitis in Pemt(-/-) mice. Moreover, HV increased the hepatic anti-inflammatory cytokine interleukin-10, reduced chemokine monocyte chemotactic protein-1 and the ER stress marker C/EBP homologous protein. Furthermore, HV normalized the expression of mitochondrial electron transport chain proteins and of proteins involved in fatty acid synthesis, acetyl-CoA carboxylase and fatty acid synthase in Pemt(-/-) mice. However, disruption of the hepatic afferent vagus nerve by capsaicin failed to reverse either the protection against the HFD-induced obesity or the development of HF-induced steatohepatitis in Pemt(-/-) mice. Neuronal signals via the hepatic vagus nerve contribute to the development of steatohepatitis and protection against obesity in HFD fed Pemt(-/-) mice. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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

The Role of Baseline Vagal Tone in Dealing with a Stressor during Face to Face and Computer-Based Social Interactions.

PubMed

Rigoni, Daniele; Morganti, Francesca; Braibanti, Paride

2017-01-01

Facing a stressor involves a cardiac vagal tone response and a feedback effect produced by social interaction in visceral regulation. This study evaluated the contribution of baseline vagal tone and of social engagement system (SES) functioning on the ability to deal with a stressor. Participants ( n = 70) were grouped into a minimized social interaction condition (procedure administered through a PC) and a social interaction condition (procedure administered by an experimenter). The State Trait Anxiety Inventory, the Social Interaction Anxiety Scale, the Emotion Regulation Questionnaire and a debriefing questionnaire were completed by the subjects. The baseline vagal tone was registered during the baseline, stressor and recovery phases. The collected results highlighted a significant effect of the baseline vagal tone on vagal suppression. No effect of minimized vs. social interaction conditions on cardiac vagal tone during stressor and recovery phases was detected. Cardiac vagal tone and the results of the questionnaires appear to be not correlated. The study highlighted the main role of baseline vagal tone on visceral regulation. Some remarks on SES to be deepen in further research were raised.

The Role of Baseline Vagal Tone in Dealing with a Stressor during Face to Face and Computer-Based Social Interactions

PubMed Central

Rigoni, Daniele; Morganti, Francesca; Braibanti, Paride

2017-01-01

Facing a stressor involves a cardiac vagal tone response and a feedback effect produced by social interaction in visceral regulation. This study evaluated the contribution of baseline vagal tone and of social engagement system (SES) functioning on the ability to deal with a stressor. Participants (n = 70) were grouped into a minimized social interaction condition (procedure administered through a PC) and a social interaction condition (procedure administered by an experimenter). The State Trait Anxiety Inventory, the Social Interaction Anxiety Scale, the Emotion Regulation Questionnaire and a debriefing questionnaire were completed by the subjects. The baseline vagal tone was registered during the baseline, stressor and recovery phases. The collected results highlighted a significant effect of the baseline vagal tone on vagal suppression. No effect of minimized vs. social interaction conditions on cardiac vagal tone during stressor and recovery phases was detected. Cardiac vagal tone and the results of the questionnaires appear to be not correlated. The study highlighted the main role of baseline vagal tone on visceral regulation. Some remarks on SES to be deepen in further research were raised. PMID:29234291

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

PubMed

Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart

2012-07-01

The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.

Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

PubMed

Lunding, J A; Nordström, L M; Haukelid, A-O; Gilja, O H; Berstad, A; Hausken, T

2008-06-01

Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

Parenting Stressors and Young Adolescents’ Depressive Symptoms: Does High Vagal Suppression Offer Protection?

PubMed Central

Fletcher, Anne C.; Buehler, Cheryl; Buchanan, Christy M.; Weymouth, Bridget B.

2017-01-01

Grounded in a dual-risk, biosocial perspective of developmental psychopathology, this study examined the role of higher vagal suppression in providing young adolescents protection from four parenting stressors. It was expected that lower vagal suppression would increase youth vulnerability to the deleterious effects of these parenting stressors. Depressive symptoms were examined as a central marker of socioemotional difficulties during early adolescence. The four parenting stressors examined were interparental hostility, maternal use of harsh discipline, maternal inconsistent discipline, and maternal psychological control. Participants were 68 young adolescents (Grade 6) and their mothers. Greater vagal suppression provided protection (i.e., lower depressive symptoms) from interparental hostility, harsh discipline, and maternal psychological control for boys but not for girls. PMID:27979628

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

PubMed

Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity.

PubMed

Sabetian, Parisa; Popovic, Milos R; Yoo, Paul B

2017-06-01

Differential measurement of efferent and afferent peripheral nerve activity offers a promising means of improving the clinical utility of implantable neuroprostheses. The tripolar nerve cuff electrode has historically served as the gold standard for achieving high signal-to-noise ratios (SNRs) of the recordings. However, the symmetrical geometry of this electrode array (i.e. electrically-shorted side contacts) precludes it from measuring electrical signals that can be used to obtain directional information. In this study, we investigated the feasibility of using a bipolar nerve cuff electrode to achieve high-SNR of peripheral nerve activity. A finite element model was implemented to investigate the effects of electrode design parameters-electrode length, electrode edge length (EEL), and a conductive shielding layer (CSL)-on simulated single fiber action potentials (SFAP) and also artifact noise signals (ANS). Our model revealed that the EEL was particularly effective in increasing the peak-to-peak amplitude of the SFAP (319%) and reducing the common mode ANS (67%) of the bipolar cuff electrode. By adding a CSL to the bipolar cuff electrode, the SNR was found to be 65.2% greater than that of a conventional tripolar cuff electrode. In vivo experiments in anesthetized rats confirmed that a bipolar cuff electrode can achieve a SNR that is 38% greater than that achieved by a conventional tripolar cuff electrode (p  <  0.05). The current study showed that bipolar nerve cuff electrodes can be designed to achieve SNR levels that are comparable to that of tripolar configuration. Further work is needed to confirm that these bipolar design parameters can be used to record bi-directional neural activity in a physiological setting.

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

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

PubMed

Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans

PubMed Central

Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O.

2018-01-01

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants (n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort. PMID:29740266

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans.

PubMed

Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O

2018-01-01

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants ( n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT ( p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS ( p = 0.014, post-hoc with Bonferroni correction ) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

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.

Effects of canal plugging on the vestibuloocular reflex and vestibular nerve discharge during passive and active head rotations.

PubMed

Sadeghi, Soroush G; Goldberg, Jay M; Minor, Lloyd B; Cullen, Kathleen E

2009-11-01

Mechanical occlusion (plugging) of the slender ducts of semicircular canals has been used in the clinic as well as in basic vestibular research. Here, we investigated the effect of canal plugging in two macaque monkeys on the horizontal vestibuloocular reflex (VOR) and the responses of vestibular-nerve afferents during passive head rotations. Afferent responses to active head movements were also studied. The horizontal VOR gain decreased after plugging to <0.1 for frequencies <2 Hz but rose to about 0.6 as frequency was increased to 15 Hz. Afferents innervating plugged horizontal canals had response sensitivities that increased with the frequency of passive rotations from <0.01 (spikes/s)/( degrees/s) at 0.5 Hz to values of about 0.2 and 0.5 (spikes/s)/( degrees/s) at 8 Hz for regular and irregular afferents, respectively (<50% of responses in controls). An increase in phase lead was also noted following plugging in afferent discharge, but not in the VOR. Because the phase discrepancy between the VOR and afferent discharge is much larger than that seen in control animals, this suggests that central adaptation shapes VOR dynamics following plugging. The effect of canal plugging on afferent responses can be modeled as an increase in stiffness and a reduction in the dominant time constant and gain in the transfer function describing canal dynamics. Responses were also evident during active head rotations, consistent with the frequency content of these movements. We conclude that canal plugging in macaques is effective only at frequencies <2 Hz. At higher frequencies, afferents show significant responses, with a nearly 90 degrees phase lead, such that they encode near-rotational acceleration. Our results demonstrate that afferents innervating plugged canals respond robustly during voluntary movements, a finding that has implications for understanding the effects of canal plugging in clinical practice.

Effects of Canal Plugging on the Vestibuloocular Reflex and Vestibular Nerve Discharge During Passive and Active Head Rotations

PubMed Central

Sadeghi, Soroush G.; Goldberg, Jay M.; Minor, Lloyd B.

2009-01-01

Mechanical occlusion (plugging) of the slender ducts of semicircular canals has been used in the clinic as well as in basic vestibular research. Here, we investigated the effect of canal plugging in two macaque monkeys on the horizontal vestibuloocular reflex (VOR) and the responses of vestibular-nerve afferents during passive head rotations. Afferent responses to active head movements were also studied. The horizontal VOR gain decreased after plugging to <0.1 for frequencies <2 Hz but rose to about 0.6 as frequency was increased to 15 Hz. Afferents innervating plugged horizontal canals had response sensitivities that increased with the frequency of passive rotations from <0.01 (spikes/s)/(°/s) at 0.5 Hz to values of about 0.2 and 0.5 (spikes/s)/(°/s) at 8 Hz for regular and irregular afferents, respectively (<50% of responses in controls). An increase in phase lead was also noted following plugging in afferent discharge, but not in the VOR. Because the phase discrepancy between the VOR and afferent discharge is much larger than that seen in control animals, this suggests that central adaptation shapes VOR dynamics following plugging. The effect of canal plugging on afferent responses can be modeled as an increase in stiffness and a reduction in the dominant time constant and gain in the transfer function describing canal dynamics. Responses were also evident during active head rotations, consistent with the frequency content of these movements. We conclude that canal plugging in macaques is effective only at frequencies <2 Hz. At higher frequencies, afferents show significant responses, with a nearly 90° phase lead, such that they encode near-rotational acceleration. Our results demonstrate that afferents innervating plugged canals respond robustly during voluntary movements, a finding that has implications for understanding the effects of canal plugging in clinical practice. PMID:19726724

Parenting stressors and young adolescents' depressive symptoms: Does high vagal suppression offer protection?

PubMed

Fletcher, Anne C; Buehler, Cheryl; Buchanan, Christy M; Weymouth, Bridget B

2017-03-01

Grounded in a dual-risk, biosocial perspective of developmental psychopathology, this study examined the role of higher vagal suppression in providing young adolescents protection from four parenting stressors. It was expected that lower vagal suppression would increase youth vulnerability to the deleterious effects of these parenting stressors. Depressive symptoms were examined as a central marker of socioemotional difficulties during early adolescence. The four parenting stressors examined were interparental hostility, maternal use of harsh discipline, maternal inconsistent discipline, and maternal psychological control. Participants were 68 young adolescents (Grade 6) and their mothers. Greater vagal suppression provided protection (i.e., lower depressive symptoms) from interparental hostility, harsh discipline, and maternal psychological control for boys but not for girls. Copyright © 2016 Elsevier Inc. All rights reserved.

Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection.

PubMed

Villarreal-Calderon, Rafael; Torres-Jardón, Ricardo; Palacios-Moreno, Juan; Osnaya, Norma; Pérez-Guillé, Beatriz; Maronpot, Robert R; Reed, William; Zhu, Hongtu; Calderón-Garcidueñas, Lilian

2010-12-01

Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1β), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1β P<.001). Mexico City mice had olfactory bulb upregulation of CD14 (P=.002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration. © The Author(s) 2010

Effects of Eucommia leaf extracts on autonomic nerves, body temperature, lipolysis, food intake, and body weight.

PubMed

Horii, Yuko; Tanida, Mamoru; Shen, Jiao; Hirata, Tetsuya; Kawamura, Naomi; Wada, Atsunori; Nagai, Katsuya

2010-08-02

Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Hair cell tufts and afferent innervation of the bullfrog crista ampullaris

NASA Technical Reports Server (NTRS)

Myers, Steven F.; Lewis, Edwin R.

1990-01-01

Within the bullfrog semicircular canal crista, hair cell tuft types were defined and mapped with the aid of scanning electron microscopy. Dye-filled planar afferent axons had mean distal axonal diameters of 1.6-4.9 microns, highly branched arbors, and contacted 11-24 hair cells. Dye-filled isthmus afferent axons had mean distal axonal diameters of 1.8-7.9 microns, with either small or large field arbors contacting 4-9 or 25-31 hair cells. The estimated mean number of contacts per innervated hair cell was 2.2 for planar and 1.3 for isthmus afferent neurons. Data on evoked afferent responses were available only for isthmus units that were observed to respond to our microrotational stimuli. Of 21 such afferent neurons, eight were successfully dye-filled. Within this sample, high-gain units had large field arbors and lower-gain units had small field arbors. The sensitivity of each afferent neuron was analyzed in terms of noise equivalent input (NEI), the stimulus amplitude for which the afferent response amplitude is just equivalent to the rms deviation of the instantaneous spike rate. NEI for isthmus units varied from 0.63 to 8.2 deg/s; the mean was 3.2 deg/s.

Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis.

PubMed

Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A

2010-09-01

Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.

Mothers’ Responses to Children’s Negative Emotions and Child Emotion Regulation: The Moderating Role of Vagal Suppression

PubMed Central

Perry, Nicole B.; Calkins, Susan D.; Nelson, Jackie A.; Leerkes, Esther M.; Marcovitch, Stuart

2011-01-01

The current study examined the moderating effect of children’s cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and non-supportive responses) and children’s emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children’s negative emotions and children’s regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children’s vagal suppression moderated the association between mothers’ non-supportive emotion socialization and children’s emotion regulation behaviors such that non-supportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children’s emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against non-supportive emotion socialization. PMID:22072217

Sciatic Nerve Stimulation and its Effects on Upper Airway Resistance in the Anesthetized Rabbit Model Relevant to Sleep Apnea.

PubMed

Schiefer, Matthew; Gamble, Jenniffer; Strohl, Kingman Perkins

2018-06-07

Obstructive sleep apnea (OSA) is a disorder characterized by collapse of the velopharynx and/or oropharynx during sleep when drive to the upper airway is reduced. Here, we explore an indirect approach for activation of upper airway muscles which might affect airway dynamics- unilateral electrical stimulation of the afferent fibers of the sciatic nerve- in an anesthetized rabbit model. A nerve cuff electrode was placed around the sciatic and hypoglossal nerves to deliver stimulus while air flow, air pressure, and alae nasi electromyogram (EMG) were monitored both prior to and after sciatic transection. Sciatic nerve stimulation increased respiratory effort, rate, and alae nasi EMG, which persisted for seconds after stimulation; however, upper airway resistance was unchanged. Hypoglossal stimulation reduced resistance without altering drive. While sciatic nerve stimulation is not ideal for treating obstructive sleep apnea, it remains a target for altering respiratory drive.

Human sinus arrhythmia as an index of vagal cardiac outflow

NASA Technical Reports Server (NTRS)

Eckberg, D. L.

1983-01-01

The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.

Patterns of motor activity in the isolated nerve cord of the octopus arm.

PubMed

Gutfreund, Yoram; Matzner, Henry; Flash, Tamar; Hochner, Binyamin

2006-12-01

The extremely flexible octopus arm provides a unique opportunity for studying movement control in a highly redundant motor system. We describe a novel preparation that allows analysis of the peripheral nervous system of the octopus arm and its interaction with the muscular and mechanosensory elements of the arm's intrinsic muscular system. First we examined the synaptic responses in muscle fibers to identify the motor pathways from the axial nerve cord of the arm to the surrounding musculature. We show that the motor axons project to the muscles via nerve roots originating laterally from the arm nerve cord. The motor field of each nerve is limited to the region where the nerve enters the arm musculature. The same roots also carry afferent mechanosensory information from the intrinsic muscle to the axial nerve cord. Next, we characterized the pattern of activity generated in the dorsal roots by electrically stimulating the axial nerve cord. The evoked activity, although far reaching and long lasting, cannot alone account for the arm extension movements generated by similar electrical stimulation. The mismatch between patterns of activity in the isolated cord and in an intact arm may stem from the involvement of mechanosensory feedback in natural arm extension.

Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis

PubMed Central

McAllen, Robin M; Salo, Lauren M; Paton, Julian F R; Pickering, Anthony E

2011-01-01

Abstract Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmissionin vivoare poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart–brainstem preparation. The atria were stabilisedin situpreserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart. PMID:22005679

Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

NASA Astrophysics Data System (ADS)

Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

2009-10-01

Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity

NASA Astrophysics Data System (ADS)

Sabetian, Parisa; Popovic, Milos R.; Yoo, Paul B.

2017-06-01

Objective. Differential measurement of efferent and afferent peripheral nerve activity offers a promising means of improving the clinical utility of implantable neuroprostheses. The tripolar nerve cuff electrode has historically served as the gold standard for achieving high signal-to-noise ratios (SNRs) of the recordings. However, the symmetrical geometry of this electrode array (i.e. electrically-shorted side contacts) precludes it from measuring electrical signals that can be used to obtain directional information. In this study, we investigated the feasibility of using a bipolar nerve cuff electrode to achieve high-SNR of peripheral nerve activity. Approach. A finite element model was implemented to investigate the effects of electrode design parameters—electrode length, electrode edge length (EEL), and a conductive shielding layer (CSL)—on simulated single fiber action potentials (SFAP) and also artifact noise signals (ANS). Main results. Our model revealed that the EEL was particularly effective in increasing the peak-to-peak amplitude of the SFAP (319%) and reducing the common mode ANS (67%) of the bipolar cuff electrode. By adding a CSL to the bipolar cuff electrode, the SNR was found to be 65.2% greater than that of a conventional tripolar cuff electrode. In vivo experiments in anesthetized rats confirmed that a bipolar cuff electrode can achieve a SNR that is 38% greater than that achieved by a conventional tripolar cuff electrode (p  <  0.05). Significance. The current study showed that bipolar nerve cuff electrodes can be designed to achieve SNR levels that are comparable to that of tripolar configuration. Further work is needed to confirm that these bipolar design parameters can be used to record bi-directional neural activity in a physiological setting.

Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection

PubMed Central

WANG, BAOXIN; YUAN, JUNJIE; XU, JIAFENG; XIE, JIN; WANG, GUOLIANG; DONG, PIN

2016-01-01

Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury. PMID:26677138

Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection.

PubMed

Wang, Baoxin; Yuan, Junjie; Xu, Jiafeng; Xie, Jin; Wang, Guoliang; Dong, Pin

2016-02-01

Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain‑derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury.

Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

PubMed Central

Mangum, Tyler S.; Sidhu, Simranjit K.; Weavil, Joshua C.; Hureau, Thomas J.; Jessop, Jacob E.; Bledsoe, Amber D.; Richardson, Russell S.; Amann, Markus

2016-01-01

Key points The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise‐induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle.Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive locomotor muscle afferents during a 5 km cycling time trial.The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural ‘drive’ to working locomotor muscle and limits the exercise‐induced intramuscular metabolic perturbation.Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance. Abstract To investigate the role of metabo‐ and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise‐induced changes in intramuscular metabolites were determined using liquid and gas chromatography‐mass spectrometry. Quadriceps fatigue was quantified by pre‐ to post‐exercise changes in potentiated quadriceps twitch torque (ΔQTsingle) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial

Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways.

PubMed

Dideriksen, Jakob L; Muceli, Silvia; Dosen, Strahinja; Laine, Christopher M; Farina, Dario

2015-02-01

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation, but electrically evoked muscle activation is in several ways different from voluntary muscle contractions. These differences lead to challenges in the use of NMES for restoring muscle function. We investigated the use of low-current, high-frequency nerve stimulation to activate the muscle via the spinal motoneuron (MN) pool to achieve more natural activation patterns. Using a novel stimulation protocol, the H-reflex responses to individual stimuli in a train of stimulation pulses at 100 Hz were reliably estimated with surface EMG during low-level contractions. Furthermore, single motor unit recruitment by afferent stimulation was analyzed with intramuscular EMG. The results showed that substantially elevated H-reflex responses were obtained during 100-Hz stimulation with respect to a lower stimulation frequency. Furthermore, motor unit recruitment using 100-Hz stimulation was not fully synchronized, as it occurs in classic NMES, and the discharge rates differed among motor units because each unit was activated only after a specific number of stimuli. The most likely mechanism behind these observations is the temporal summation of subthreshold excitatory postsynaptic potentials from Ia fibers to the MNs. These findings and their interpretation were also verified by a realistic simulation model of afferent stimulation of a MN population. These results suggest that the proposed stimulation strategy may allow generation of considerable levels of muscle activation by motor unit recruitment that resembles the physiological conditions. Copyright © 2015 the American Physiological Society.

Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat.

PubMed

Clark, F J; Matthews, P B; Muir, R B

1981-02-01

1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor.2. When the amplitude of vibration was 50 mum, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 mum vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut.3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 mum vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 mum vibration; at the same time the reflex tension increased.4. Additional, indirect evidence favouring widespread security of Ia driving by 50 mum vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action.5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general

Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat

PubMed Central

Clark, F. J.; Matthews, P. B. C.; Muir, R. B.

1981-01-01

1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor. 2. When the amplitude of vibration was 50 μm, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 μm vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut. 3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 μm vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 μm vibration; at the same time the reflex tension increased. 4. Additional, indirect evidence favouring widespread security of Ia driving by 50 μm vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action. 5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general

Vibratory Adaptation of Cutaneous Mechanoreceptive Afferents