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Sample records for rat cerebellar cortex

  1. Role of Muscarinic Acetylcholine Receptor-2 in the Cerebellar Cortex in Cardiovascular Modulation in Anaesthetized Rats.

    PubMed

    Zhang, Changzheng; Sun, Tingzhe; Zhou, Peiling; Zhu, Qingfeng; Zhang, Liefeng

    2016-04-01

    Our previous investigations have demonstrated that microinjection of acetylcholine (ACh) or muscarinic ACh receptor activation in the cerebellar cortex induces a systemic blood pressure depressor response. This study aimed to determine the role of muscarinic ACh receptor-2 (M2 receptor) in the cerebellar cortex in cardiovascular function regulation in rats. A nonselective muscarinic receptor agonist (oxotremorine M, OXO; 30 mM), a selective M2 receptor agonist (arecaidine but-2-ynyl ester tosylate, ABET; 3, 10, and 30 mM), 30 mM OXO mixed with a selective M2 receptor antagonist (methoctramine hydrate, MCT; 0.3, 1, and 3 mM), and normal saline (0.9 % NaCl) were separately microinjected (0.5 µl/5 s) into the cerebellar cortex (lobule VI) of anaesthetized rats. We measured the mean arterial pressure (MAP), maximum change in MAP, and reactive time (RT; the duration required for the blood pressure to return to basal levels), heart rate (HR) and the maximum change in HR during the RT in response to drug activation. The results demonstrated that ABET dose-dependently decreased MAP and HR, increased the maximum change in MAP and the maximum change in HR, and prolonged the RT. Furthermore, MCT dose-dependently blocked the OXO-mediated cardiovascular depressor response. This study provides the first evidence that M2 receptors in the cerebellar cortex are involved in cardiovascular regulation, the activation of which evokes significant depressor and bradycardic responses.

  2. Synapse-to-neuron ratios in rat cerebellar cortex following lengthy periods of undernutrition.

    PubMed Central

    Warren, M A; Bedi, K S

    1990-01-01

    Black and white hooded Lister rats were undernourished for various times up to 150 days of age; some of them were nutritionally rehabilitated from 75 days. Undernourished rats weighed significantly less than well-fed controls at all ages studied. After embedding in resin, sections of cerebellar cortex were cut and examined at the light and electron microscopical levels using traditional morphometric methods. Undernourished rats showed significant deficits in synapse-to-neuron ratio, compared with controls, at 21 days of age. This deficit disappeared by 75 days despite continued undernutrition. Indeed, there was no alteration in this ratio even when undernutrition was extended up to 150 days even though the ratio for the controls decreased after that period. Rats undernourished from birth to 75 days and subsequently rehabilitated to 150 days had significantly more synapses per neuron than controls. The functional sequelae of these morphological changes remain unknown. Images Fig. 1 Fig. 2 PMID:2254161

  3. Transcranial theta-burst stimulation alters GLT-1 and vGluT1 expression in rat cerebellar cortex.

    PubMed

    Mancic, Bojana; Stevanovic, Ivana; Ilic, Tihomir V; Djuric, Ana; Stojanovic, Ivana; Milanovic, Sladjan; Ninkovic, Milica

    2016-11-01

    Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in activity of excitatory and inhibitory systems as well as redox homeostasis. Our aim was to investigate the effect of single (SS) and repeated session (RS) of intermittent and continuous theta-burst stimulation (iTBS; cTBS) on the expression of vesicular and plasmatic glutamate transporters 1 (vGluT1 and GLT-1), glial fibrillary acidic protein (GFAP) and influence on oxidative status in rats cerebellar tissue and plasma. Redox state parameters in cerebellar tissue and plasma were assessed 24 h after single and 48 h after the last TBS session. Molecular changes were examined by immunofluorescence. Stimulation significantly increased thiol groups (SH) in tissue of SS iTBS group, and decreased in iTBS RS. Activity of glucose-6-phosphate-dehydrogenase (G6PD) was increased markedly in cTBS RS. Immunoreactivity of vGluT1 in cTBS RS decreased, while GLT-1 increased in cTBS SS and cTBS RS, compared to control. Present study gives insight in molecular and biochemical mechanisms by which iTBS and cTBS exerts its effects on rats cerebellar cortex.

  4. [Cytochemical research on the matrix activity and status of the histone component of the neurocyte chromatin in the rat cerebellar cortex during postnatal differentiation].

    PubMed

    Grigor'eva, A V; Iarygin, V N

    1986-08-01

    Evident differences in the ammoniacal silver staining pattern of histones were demonstrated for neurones of different layers of adult rat cerebellar cortex. These differences were formed during postnatal differentiation. It has been also shown for Purkinje and granular cells that time-course of age-dependent changes in histone staining are not coincident with that for template activity of these cells.

  5. Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres.

    PubMed

    Leergaard, Trygve B; Lillehaug, Sveinung; De Schutter, Erik; Bower, James M; Bjaalie, Jan G

    2006-11-01

    The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.

  6. Importance of nitric oxide for local increases of blood flow in rat cerebellar cortex during electrical stimulation.

    PubMed Central

    Akgören, N; Fabricius, M; Lauritzen, M

    1994-01-01

    The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, including the brain. We explored the possibility that NO might be of importance for the increase of cerebral blood flow (CBF) associated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. The evoked increases of CBF were frequency-dependent, being larger on than off the parallel fiber tracts, suggesting that conduction along parallel fibers and synaptic activation of target cells were important for the increase of CBF. This was verified experimentally since the evoked CBF increases were abolished by tetrodotoxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in the increase of CBF associated with neuronal activation. NO synthase inhibition by topical application of NG-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while NG-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors and NO synthase had no further suppressing effect on the blood flow increase than either substance alone, suggesting that the NO-dependent flow rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is involved in the transduction mechanism between neuronal activity and increased CBF. Images PMID:7517038

  7. Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine morphology.

    PubMed

    Bauer, David J; Peterson, Todd C; Swain, Rodney A

    2014-01-28

    Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Experiments in rats examining the functional role of this cerebellothalamocortical pathway have demonstrated the development of visuospatial and motivational deficits following lesions of the dentate nuclei, in the absence of motor impairment. These behavioral deficits possibly occur due to structural modifications of the cerebral cortex secondary to loss of cerebellar input. The current study characterized morphological alterations in prefrontal cortex important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions. Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30-day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for analysis. Measures of branch length and spine density revealed no differences between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls, with reductions of 33% in the basilar arbor and 28% in the apical arbor. Although expected pruning of branches and spines did not occur, the results are consistent with the hypothesis that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.

  8. VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

    PubMed Central

    2011-01-01

    Background The aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1. Results The examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons. Conclusion The present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins. PMID:22094010

  9. Caytaxin Deficiency Disrupts Signaling Pathways in Cerebellar Cortex

    PubMed Central

    Xiao, Jianfeng; Gong, Suzhen; LeDoux, Mark S.

    2007-01-01

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as a site of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time RT-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and calcium-transporting plasma membrane ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex. PMID:17092653

  10. Caytaxin deficiency disrupts signaling pathways in cerebellar cortex.

    PubMed

    Xiao, J; Gong, S; Ledoux, M S

    2007-01-19

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as sites of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time reverse transcriptase-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and plasma membrane calcium-dependent ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex.

  11. An integrator circuit in cerebellar cortex.

    PubMed

    Maex, Reinoud; Steuber, Volker

    2013-09-01

    The brain builds dynamic models of the body and the outside world to predict the consequences of actions and stimuli. A well-known example is the oculomotor integrator, which anticipates the position-dependent elasticity forces acting on the eye ball by mathematically integrating over time oculomotor velocity commands. Many models of neural integration have been proposed, based on feedback excitation, lateral inhibition or intrinsic neuronal nonlinearities. We report here that a computational model of the cerebellar cortex, a structure thought to implement dynamic models, reveals a hitherto unrecognized integrator circuit. In this model, comprising Purkinje cells, molecular layer interneurons and parallel fibres, Purkinje cells were able to generate responses lasting more than 10 s, to which both neuronal and network mechanisms contributed. Activation of the somatic fast sodium current by subthreshold voltage fluctuations was able to maintain pulse-evoked graded persistent activity, whereas lateral inhibition among Purkinje cells via recurrent axon collaterals further prolonged the responses to step and sine wave stimulation. The responses of Purkinje cells decayed with a time-constant whose value depended on their baseline spike rate, with integration vanishing at low (< 1 per s) and high rates (> 30 per s). The model predicts that the apparently fast circuit of the cerebellar cortex may control the timing of slow processes without having to rely on sensory feedback. Thus, the cerebellar cortex may contain an adaptive temporal integrator, with the sensitivity of integration to the baseline spike rate offering a potential mechanism of plasticity of the response time-constant.

  12. [Ultrastructure of the cortex of the cerebellar nodulus in rats after a flight on the biosatellite Kosmos-1514].

    PubMed

    Krasnov, I B; D'iachkova, L N

    1986-01-01

    The ultrastructure of moss fibers and granule cells of the cortex of the cerebellum nodulus of rats flown for 5 days onboard the biosatellite Cosmos-1514 and exposed to 1 g for 6-8 hours upon return to Earth is indicative of an excess excitation of terminals of moss fibers and excitation of granule cells. The excitation of moss fiber terminals reflect the excitatory state of hair cells of the otolith apparatus and neurons of the vestibular ganglion produced by the effect of 1 g after exposure to microgravity. This state can be viewed as evidence of a greater sensitivity of the hair cell of the otolith organ--neuron of the vestibular ganglion system during exposure to microgravity. It is hypothesized that the sensitivity of this system of other mammals may also increase in microgravity.

  13. Neocortical networks entrain neuronal circuits in cerebellar cortex

    PubMed Central

    Roš, Hana; Sachdev, Robert N. S.; Yu, Yuguo; Šestan, Nenad; McCormick, David A.

    2011-01-01

    Activity in neocortex is often characterized by synchronized oscillations of neurons and networks, resulting in the generation of a local field potential and electroencephalogram. Do the neuronal networks of the cerebellum also generate synchronized oscillations and are they under the influence of those in the neocortex? Here we show that in the absence of any overt external stimulus, the cerebellar cortex generates a slow oscillation that is correlated with that of the neocortex. Disruption of the neocortical slow oscillation abolishes the cerebellar slow oscillation, whereas blocking cerebellar activity has no overt effect on the neocortex. We provide evidence that the cerebellar slow oscillation results in part from the activation of granule, Golgi, and Purkinje neurons. In particular, we show that granule and Golgi cells discharge trains of single spikes, and Purkinje cells generate complex spikes, during the Up state of the slow oscillation. Purkinje cell simple spiking is weakly related to the cerebellar and neocortical slow oscillation in a minority of cells. Our results indicate that the cerebellum generates rhythmic network activity that can be recorded as an LFP in the anesthetized animal, which is driven by synchronized oscillations of the neocortex. Furthermore, we show that correlations between neocortical and cerebellar LFPs persist in the awake animal, indicating that neocortical circuits modulate cerebellar neurons in a similar fashion in natural behavioral states. Thus, the projection neurons of the neocortex collectively exert a driving and modulatory influence on cerebellar network activity. PMID:19692605

  14. Early degeneration of the cerebellar cortex, particularly the granular cells.

    PubMed

    Bugiani, O; Berio, A; Di Stefano, A; Mangiante, G; Mancardi, G L; Leonardi, A

    1978-12-07

    An 8 month old infant, who died of severe gastroenteritis, presented a degeneration of the cerebellar cortex involving cells arising from the outer granular layer as well as Purkinje and Golgi II cells. Residual Purkinje cells showed vacuolar change of the cell body and dendritic abnormalities. Related lesions were atrophy of the inferior olives and degeneration of the mossy fibers.

  15. Long lasting cerebellar alterations after perinatal asphyxia in rats.

    PubMed

    Campanille, Verónica; Saraceno, G Ezequiel; Rivière, Stéphanie; Logica, Tamara; Kölliker, Rodolfo; Capani, Francisco; Castilla, Rocío

    2015-07-01

    The developing brain may be particularly vulnerable to injury before, at and after birth. Among possible insults, hypoxia suffered as a consequence of perinatal asphyxia (PA) exhibits the highest incidence levels and the cerebellar circuitry appears to be particularly susceptible, as the cellular makeup and the quantity of inputs change quickly during days and weeks following birth. In this work, we have used a murine model to induce severe global PA in rats at the time of birth. Short-term cerebellar alterations within this PA model have been previously reported but whether such alterations remain in adulthood has not been conclusively determined yet. For this reason, and given the crucial cerebellar role in determining connectivity patterns in the brain, the aim of our work is to unveil long-term cerebellum histomorphology following a PA insult. Morphological and cytological neuronal changes and glial reaction in the cerebellar cortex were analyzed at postnatal 120 (P120) following injury performed at birth. As compared to control, PA animals exhibited: (1) an increase in molecular and granular thickness, both presenting lower cellular density; (2) a disarrayed Purkinje cell layer presenting a higher number of anomalous calbindin-stained cells. (3) focal swelling and marked fragmentation of microtubule-associated protein 2 (MAP-2) in Purkinje cell dendrites and, (4) an increase in glial fibrillary acidic protein (GFAP) expression in Bergmann cells and the granular layer. In conclusion, we demonstrate that PA produces long-term damage in cellular histomorphology in rat cerebellar cortex which could be involved in the pathogenesis of cognitive deficits observed in both animals and humans.

  16. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  17. Back to front: cerebellar connections and interactions with the prefrontal cortex.

    PubMed

    Watson, Thomas C; Becker, Nadine; Apps, Richard; Jones, Matthew W

    2014-01-01

    Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN) in awake, behaving rats evokes distinct local field potential (LFP) responses (onset latency ~13 ms) in the prelimbic (PrL) subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz). Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

  18. Microarchitectural changes during development of the cerebellar cortex.

    PubMed

    Mecha, Miriam; Peña-Melián, Angel L; Blanco, Maria J

    2010-01-01

    The cerebellum is a highly conserved structure in the Central Nervous System (CNS) of vertebrates, and is involved in the coordination of voluntary motor behaviour. Supporting this function, the cerebellar cortex presents a layered structure which requires a precise spatial and temporal coordination of proliferation, migration and differentiation events. One of the characteristics of the developing cortex is the formation of the external granule cell layer (EGL) in the outermost part. The EGL is a highly proliferative transient layer which disappears when cells migrate inwards to form the inner granule cell layer. The balance between proliferation and migration leads to changes in EGL thickness, and might be related to "indentations" observed in the surface of the developing chick cerebellum. We have extended the observation of this feature to quail and mouse, supporting the idea that this phenomenon forms part of the mechanisms of cerebellar morphogenesis. Different factors involved in both mitotic activity and migration were analyzed in this study. Our results indicate that proliferation, more than formation of raphes for cell migration, is involved in the formation of indentations in the EGL. In addition, we show that vessels penetrating from the pial surface divide the EGL into regular regions at the time of the appearance of bulges and furrows. We conclude that indentations are the result of a coincidence in time of both the increase in thickness of the EGL and the establishment of the embryonic vascular pattern, which confers a characteristic transitory morphology to the surface of folia.

  19. Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

    PubMed

    Thürling, Markus; Kahl, Fabian; Maderwald, Stefan; Stefanescu, Roxana M; Schlamann, Marc; Boele, Henk-Jan; De Zeeuw, Chris I; Diedrichsen, Jörn; Ladd, Mark E; Koekkoek, Sebastiaan K E; Timmann, Dagmar

    2015-01-21

    There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded.

  20. Antenatal betamethasone produces protracted changes in anxiety-like behaviors and in the expression of microtubule-associated protein 2, brain-derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex.

    PubMed

    Pascual, Rodrigo; Valencia, Martina; Bustamante, Carlos

    2015-06-01

    Using classic Golgi staining methods, we previously showed that the administration of synthetic glucocorticoid betamethasone in equivalent doses to those given in cases of human premature birth generates long-term alterations in Purkinje cell dendritic development in the cerebellar cortex. In the present study, we evaluated whether betamethasone alters the immunohistochemical expression of proteins that participate in cerebellar Purkinje cell dendritic development and maintenance, including microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor (BDNF) and the tyrosine kinase B receptor (TrkB), which are located predominantly in the cerebellar molecular layer where Purkinje cell dendritogenesis occurs. Consistent with our previous Golgi stain studies, we observed that animals prenatally exposed to a single course of betamethasone showed long-term alterations in the expression of MAP2, BDNF and TrkB. Additionally, these protracted molecular changes were accompanied by anxiety-like behaviors in the elevated plus maze and marble burying tests.

  1. [MORPHOFUNCTIONAL ADJUSTMENT VASCULAR AND CELLULAR COMPONENTS OF THE CEREBELLAR CORTEX IN EXPOSURE TO BODY SULFATES OF COPPER, ZINC AND IRON].

    PubMed

    Grintsova, N; Vasko, L; Kiptenko, L; Gortinsky, A; Murenets, N

    2015-09-01

    In order to analyze the morphological and morphometric reconstructions of the vascular bed, and Purkinje cells of the cerebellar cortex of rats in long-term action (for 90 days) on the body of sulphates of copper, zinc and iron, an experiment was conducted on 48 adult white male rats weighing 200-250 g in age 5-7 months. We used anatomical, morphometric, statistical and common methods of microanatomical research. It was found that the combined effect on the body of sulphates of copper and zinc, and iron in the cerebellum has enough expressive toxicity, which affects the condition of the vascular bed, and Purkinje cells. The degree of morphological transformations is in direct proportion to the duration of the experiment. In the pathogenesis of violations leading role played by hypoxia, develop signs of swelling of the cerebellar cortex with signs hemorrhagic infiltration, the severity of which is maximum on the 60th day of the experiment.

  2. Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

    PubMed

    Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

    2017-02-01

    Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

  3. Circadian oscillators in the mouse brain: molecular clock components in the neocortex and cerebellar cortex.

    PubMed

    Rath, Martin F; Rovsing, Louise; Møller, Morten

    2014-09-01

    The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum, as revealed by immunohistochemistry. These findings give reason to further pursue the physiological significance of circadian oscillators in the mouse neocortex and cerebellum.

  4. Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

    PubMed

    Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

    2015-12-01

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

  5. Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A.

    PubMed

    Zsarnovszky, Attila; Le, Hoa H; Wang, Hong-Sheng; Belcher, Scott M

    2005-12-01

    In addition to regulating estrogen receptor-dependent gene expression, 17beta-estradiol (E(2)) can directly influence intracellular signaling. In primary cultured cerebellar neurons, E(2) was previously shown to regulate growth and oncotic cell death via rapid stimulation of ERK1/2 signaling. Here we show that ERK1/2 signaling in the cerebellum of neonatal and mature rats was rapidly responsive to E(2) and during development to the environmental estrogen bisphenol A (BPA). In vivo dose-response analysis for each estrogenic compound was performed by brief (6-min) intracerebellar injection, followed by rapid fixation and phosphorylation-state-specific immunohistochemistry to quantitatively characterize changes in activated ERK1/2 (pERK) immunopositive cell numbers. Beginning on postnatal d 8, E(2) significantly influenced the number of pERK-positive cells in a cell-specific manner that was dependent on concentration and age but not sex. In cerebellar granule cells on postnatal d 10, E(2) or BPA increased pERK-positive cell numbers at low doses (10(-12) to 10(-10) M) and at higher (10(-7) to 10(-6) M) concentrations. Intermediate concentrations of either estrogenic compound did not modify basal ERK signaling. Rapid E(2)-induced increases in pERK immunoreactivity were specific to the ERK1/2 pathway as demonstrated by coinjection of the mitogen-activated, ERK-activating kinase (MEK)1/2 inhibitor U0126. Coadministration of BPA (10(-12) to 10(-10) M) with 10(-10) M E(2) dose-dependently inhibited rapid E(2)-induced ERK1/2 activation in developing cerebellar neurons. The ability of BPA to act as a highly potent E(2) mimetic and to also disrupt the rapid actions of E(2) at very low concentrations during cerebellar development highlights the potential low-dose impact of xenoestrogens on the developing brain.

  6. Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates

    PubMed Central

    Jacobs, Bob; Johnson, Nicholas L.; Wahl, Devin; Schall, Matthew; Maseko, Busisiwe C.; Lewandowski, Albert; Raghanti, Mary A.; Wicinski, Bridget; Butti, Camilla; Hopkins, William D.; Bertelsen, Mads F.; Walsh, Timothy; Roberts, John R.; Reep, Roger L.; Hof, Patrick R.; Sherwood, Chet C.; Manger, Paul R.

    2014-01-01

    Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee), carnivores (Siberian tiger, clouded leopard), cetartiodactyls (humpback whale, giraffe) and primates (human, common chimpanzee). Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317) of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant) and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967) and rodents (Palay and Chan-Palay, 1974), although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures. PMID:24795574

  7. Ultrastructural pathology of human peritumoural oedematous cerebellar cortex.

    PubMed

    Castejón, O J

    2016-01-01

    Cerebellar cortical biopsies of the peritumoural region of seven patients with cerebellar haemangioma, mesencephalic meningioma, cerebellopontine astrocytoma, cerebellopontine meningioma, and medulloblastoma of cerebellar vermis were examined by means of conventional transmission electron microscopy. Granule cells showed oedematous cytoplasm and mitochondria. Swollen Golgi cells exhibited lipofuscin granules and intranuclear inclusions. Both neuron cell types displayed swollen dendritic digits synapsing with afferent mossy fibre endings. Degenerated myelinated axons corresponding to afferent mossy and climbing fibres and efferent Purkinje cell axons were observed at the granular layer. Dense and clear ischaemic Purkinje cells established degenerated synapses with swollen parallel fibre synaptic varicosities. Degenerated Purkinje cell recurrent axonal collaterals were found at the molecular layer. Swollen and clear Bergmann glial cell cytoplasm was observed closely applied to the oedematous clear and dark Purkinje cell body, dendritic trunk, secondary and tertiary dendritic branches. Swollen climbing fibre endings featured by numerous microtubules and neurofilaments, and a decreased number of synaptic vesicles were observed making degenerated axo-spinodendritic synapses with clear and swollen dendritic spines from Purkinje, Golgi, basket and stellate cell dendrites. Swollen stellate neurons showed oedematous mitochondria. Lipofuscin-rich astrocytes and reactive phagocytic astrocytes were observed. The latter appeared engulfing haematogenous proteinaceous oedema fluid. All cerebellar neurons showed stress endoplasmic reticulum dysfunction featured by focal dilated cisterns and detachment of associated ribosomes. Myelin sheath degeneration was related with oligodendrocyte degenerating hydropic changes. The peritumoural ischaemic cerebellar nerve and glial cell abnormalities were related with neurobehavioral changes, tremor, nystagmus, dismetry and gait disturbance

  8. Precise localization of the voltage-gated potassium channel subunits Kv3.1b and Kv3.3 revealed in the molecular layer of the rat cerebellar cortex by a pre-embedding immunogold method.

    PubMed

    Puente, Nagore; Mendizabal-Zubiaga, Juan; Elezgarai, Izaskun; Reguero, Leire; Buceta, Ianire; Grandes, Pedro

    2010-10-01

    A proper motor activity relies on a correct cerebellar function. The Kv3.1 and Kv3.3 voltage-gated potassium channels are key proteins involved in cerebellar function and dysfunction, as the lack of these causes severe motor deficits. Both channel subunits are coexpressed in granule cells and are rapidly activated at relatively positive potentials to support the generation of fast action potentials. However, the contribution of each subunit to the molecular architecture of the parallel fibers, the granule cell axons, is so far unknown. The goal of this study was to elucidate the relative distribution of Kv3.1b and Kv3.3 in specific compartments of the rat parallel fibers by using a pre-embedding immunocytochemical method for electron microscopy. Numerous Kv3.1b and Kv3.3 silver-intensified gold particles were associated with membranes of parallel fiber synaptic terminals and their intervaricose segments. Kv3.1b was found in about 85% of parallel fiber synaptic terminals and in about 47% of their intervaricose portions. However, only 28% of intervaricosities and 23% of parallel fiber presynaptic boutons were Kv3.3 immunopositive. The analysis also revealed that 54% of Purkinje cell dendritic spines localized Kv3.3. Although both potassium channel subunits share localization in the same presynaptic parallel fiber compartments, the present results with the method used indicate that there are a higher percentage of parallel fibers labeled for Kv3.1b than for Kv3.3, and that the labeling intensity for each subunit is higher in specific subcompartments analyzed than in others.

  9. Cerebellar Structure and Function in Male Wistar-Kyoto Hyperactive Rats

    PubMed Central

    Thanellou, Alexandra; Green, John T.

    2014-01-01

    Previous research has suggested that the Wistar-Kyoto Hyperactive (WKHA) rat strain may model some of the behavioral features associated with attention-deficit/hyperactivity disorder (ADHD). We have shown that, in cerebellar-dependent eyeblink conditioning, WKHA emit eyeblink CRs with shortened onset latencies. To further characterize the shortened CR onset latencies seen in WKHA rats, we examined 750-ms delay conditioning with either a tone CS or a light CS, we extended acquisition training, and we included Wistar rats as an additional, outbred control strain. Our results indicated that WKHAs learned more quickly and showed a shortened CR onset latency to a tone CS compared to both Wistar-Kyoto Hypertensive (WKHT) and Wistars. WKHAs and Wistars show a lengthening of CR onset latency over conditioning with a tone CS and an increasing confinement of CRs to the later part of the tone CS (inhibition of delay). WKHAs learned more quickly to a light CS only in comparison to WKHTs and showed a shortened CR onset latency only in comparison to Wistars. Wistars showed an increasing confinement of CRs to the late part of the light CS over conditioning. We used unbiased stereology to estimate the number of Purkinje and granule cells in the cerebellar cortex of the three strains. Our results indicated that WKHAs have more granule cells than Wistars and WKHTs and more Purkinje cells than Wistars. Results are discussed in terms of CS processing and cerebellar cortical contributions to EBC. PMID:23398437

  10. Cerebellar structure and function in male Wistar-Kyoto hyperactive rats.

    PubMed

    Thanellou, Alexandra; Green, John T

    2013-04-01

    Previous research has suggested that the Wistar-Kyoto Hyperactive (WKHA) rat strain may model some of the behavioral features associated with attention-deficit/hyperactivity disorder (ADHD). We have shown that, in cerebellar-dependent eyeblink conditioning, male WKHAs emit eyeblink CRs with shortened onset latencies. To further characterize the shortened CR onset latencies seen in male WKHA rats, we examined 750-ms delay conditioning with either a tone conditional stimulus (CS) or a light CS, we extended acquisition training, and we included Wistar rats as an additional, outbred control strain. Our results indicated that WKHAs learned more quickly and showed a shortened CR onset latency to a tone CS compared to both Wistar-Kyoto Hypertensive (WKHT) and Wistars. WKHAs and Wistars show a lengthening of CR onset latency over conditioning with a tone CS and an increasing confinement of CRs to the later part of the tone CS (inhibition of delay). WKHAs learned more quickly to a light CS only in comparison to WKHTs, and showed a shortened CR onset latency only in comparison to Wistars. Wistars showed an increasing confinement of CRs to the late part of the light CS over conditioning. We used unbiased stereology to estimate the number of Purkinje and granule cells in the cerebellar cortex of the three strains. Our results indicated that WKHAs have more granule cells than Wistars and WKHTs and more Purkinje cells than Wistars. Results are discussed in terms of CS processing and cerebellar cortical contributions to EBC.

  11. The rat cortex in stereotaxic coordinates.

    PubMed

    Schober, W

    1986-01-01

    On the basis of Nissl-preparations the cortex of albino rats has been mapped cytoarchitectonically. 13 frontal sections through the cortex are illustrated with coordinates. Therewith exists a stereotaxic atlas of the cortex of the rat and one can realize exactly experimental investigations in the different cortical areas.

  12. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.

    PubMed

    Stefanescu, Maria R; Dohnalek, Moritz; Maderwald, Stefan; Thürling, Markus; Minnerop, Martina; Beck, Andreas; Schlamann, Marc; Diedrichsen, Joern; Ladd, Mark E; Timmann, Dagmar

    2015-05-01

    Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia

  13. Responses evoked in the cerebellar cortex by stimulation of the caudate nucleus in the cat

    PubMed Central

    Fox, Mary; Williams, T. D.

    1968-01-01

    1. Responses evoked in the cerebellar cortex following stimulation of caudate nucleus are described. 2. The evoked responses recorded from the surface of the cerebellar cortex were found to be of two types, one with a short (4-6 msec) latency and one with a longer (12-17 msec) latency. 3. The short latency response was maximal in the lobulus simplex, the longer latency response was maximal in paramedian lobule. 4. Following lesions in the inferior olive the longer latency response was absent. 5. Recordings from within the cerebellar cortex showed that the short latency response was uniformly distributed throughout the grey matter, the longer latency response was maximal in the region of the Purkinje cell bodies. 6. It was concluded that the short latency response was due to activation via the mossy fibres and the longer latency response to activation via the climbing fibres. 7. It was found that responses could be evoked in the cerebellum following stimulation of only the latero-ventral part of the caudate nucleus; stimulation of the rest of the nucleus caused no response in the cerebellum. This division of the caudate nucleus into two parts is similar to the subdivision of the caudate nucleus made by other workers using different criteria. PMID:5698279

  14. Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat.

    PubMed

    Hesslow, G

    1994-04-15

    The purpose of the present study was to test the hypothesis that neurones in the anterior interpositus nucleus, under the control of Purkinje cells in the c1 and c3 zones of the cerebellar cortex, exert some control over classically conditioned responses. In particular, the experiments were designed to determine whether the cerebellar control of conditioned and unconditioned responses is different. The experiments were performed on cats decerebrated rostral to the red nucleus under halothane anaesthesia. The cats were conditioned using either a 1000 Hz tone or trains of stimuli through the skin of the proximal forelimb as the conditioned stimulus, and periorbital electrical stimulation as the unconditioned stimulus. A large proportion of the animals acquired conditioned responses at normal rates. It could be shown that these were true conditioned responses and did not result from sensitization or pseudoconditioning. For instance, unpaired presentations of conditioned and unconditioned stimuli caused rapid extinction. Cerebellar areas controlling eyeblink were identified by recording climbing fibre responses in the cerebellar cortex and recording EMG activity in the eyelid evoked by stimulation of the cerebellar cortex. When single shocks of 40-70 microA were applied to these areas during the emission of conditioned eyeblink responses, the latter were strongly inhibited. The inhibition had a latency of about 10 ms and a duration of 25-75 ms. It was shown that this inhibition of the conditioned responses was topographically specific and could only be evoked from cortical sites identified as controlling eyeblink. Stimulation of the periphery of an eyeblink area caused little or no inhibition. The effect of cortical stimulation on unconditioned reflex responses in the orbicularis oculi muscle was also tested. Some inhibition of unconditioned responses was observed, but quantitative analysis showed that this inhibition was considerably weaker than the corresponding

  15. Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat.

    PubMed Central

    Hesslow, G

    1994-01-01

    The purpose of the present study was to test the hypothesis that neurones in the anterior interpositus nucleus, under the control of Purkinje cells in the c1 and c3 zones of the cerebellar cortex, exert some control over classically conditioned responses. In particular, the experiments were designed to determine whether the cerebellar control of conditioned and unconditioned responses is different. The experiments were performed on cats decerebrated rostral to the red nucleus under halothane anaesthesia. The cats were conditioned using either a 1000 Hz tone or trains of stimuli through the skin of the proximal forelimb as the conditioned stimulus, and periorbital electrical stimulation as the unconditioned stimulus. A large proportion of the animals acquired conditioned responses at normal rates. It could be shown that these were true conditioned responses and did not result from sensitization or pseudoconditioning. For instance, unpaired presentations of conditioned and unconditioned stimuli caused rapid extinction. Cerebellar areas controlling eyeblink were identified by recording climbing fibre responses in the cerebellar cortex and recording EMG activity in the eyelid evoked by stimulation of the cerebellar cortex. When single shocks of 40-70 microA were applied to these areas during the emission of conditioned eyeblink responses, the latter were strongly inhibited. The inhibition had a latency of about 10 ms and a duration of 25-75 ms. It was shown that this inhibition of the conditioned responses was topographically specific and could only be evoked from cortical sites identified as controlling eyeblink. Stimulation of the periphery of an eyeblink area caused little or no inhibition. The effect of cortical stimulation on unconditioned reflex responses in the orbicularis oculi muscle was also tested. Some inhibition of unconditioned responses was observed, but quantitative analysis showed that this inhibition was considerably weaker than the corresponding

  16. Surface-based atlases of cerebellar cortex in the human, macaque, and mouse

    NASA Technical Reports Server (NTRS)

    Van Essen, David C.

    2002-01-01

    This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

  17. Robustness effect of gap junctions between Golgi cells on cerebellar cortex oscillations

    PubMed Central

    2011-01-01

    Background Previous one-dimensional network modeling of the cerebellar granular layer has been successfully linked with a range of cerebellar cortex oscillations observed in vivo. However, the recent discovery of gap junctions between Golgi cells (GoCs), which may cause oscillations by themselves, has raised the question of how gap-junction coupling affects GoC and granular-layer oscillations. To investigate this question, we developed a novel two-dimensional computational model of the GoC-granule cell (GC) circuit with and without gap junctions between GoCs. Results Isolated GoCs coupled by gap junctions had a strong tendency to generate spontaneous oscillations without affecting their mean firing frequencies in response to distributed mossy fiber input. Conversely, when GoCs were synaptically connected in the granular layer, gap junctions increased the power of the oscillations, but the oscillations were primarily driven by the synaptic feedback loop between GoCs and GCs, and the gap junctions did not change oscillation frequency or the mean firing rate of either GoCs or GCs. Conclusion Our modeling results suggest that gap junctions between GoCs increase the robustness of cerebellar cortex oscillations that are primarily driven by the feedback loop between GoCs and GCs. The robustness effect of gap junctions on synaptically driven oscillations observed in our model may be a general mechanism, also present in other regions of the brain. PMID:22330240

  18. A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

    PubMed

    McBride, Devin W; Nowrangi, Derek; Kaur, Harpreet; Wu, Guangyong; Huang, Lei; Lekic, Tim; Tang, Jiping; Zhang, John H

    2017-01-01

    Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

  19. Neurotoxicological effects of nicotine on the embryonic development of cerebellar cortex of chick embryo during various stages of incubation.

    PubMed

    El-Beltagy, Abd El-Fattah B M; Abou-El-Naga, Amoura M; Sabry, Dalia M

    2015-10-01

    Long-acting nicotine is known to exert pathological effects on almost all tissues including the cerebellar cortex. The present work was designed to elucidate the effect of nicotine on the development of cerebellar cortex of chick embryo during incubation period. The fertilized eggs of hen (Gallus gallus domesticus) were injected into the air space by a single dose of long acting nicotine (1.6 mg/kg/egg) at the 4th day of incubation. The embryos were taken out of the eggs on days 8, 12 and 16 of incubation. The cerebellum of the control and treated embryos at above ages were processed for histopathological examination. The TEM were examined at 16th day of incubation. The results of the present study revealed that, exposure to long-acting nicotine markedly influence the histogenesis of cerebellar cortex of chick embryo during the incubation period. At 8th day of incubation, nicotine delayed the differentiation of the cerebellar analge; especially the external granular layer (EGL) and inner cortical layer (ICL). Furthermore, at 12th day of incubation, the cerebellar foliation was irregular and the Purkinje cells not recognized. By 16th day of incubation, the cerebellar foliations were irregular with interrupted cerebellar cortex and irregular arrangement of Purkinje cells. Immunohistochemical analysis for antibody P53 protein revealed that the cerebellar cortex in all stages of nicotine treated groups possessed a moderate to weak reaction for P53 protein however; this reaction was markedly stronger in the cerebellar cortex of control groups. Moreover, the flow cytometric analysis confirmed that the percentage of apoptosis in control group was significantly higher compared with that of nicotine treated group. At the TEM level, the cerebellar Purkinje cells of 16th day of treated groups showed multiple subcellular alterations in compared with those of the corresponding control group. Such changes represented by appearing of vacuolated mitochondria, cisternal

  20. Reevaluation of the Beam and Radial Hypotheses of Parallel Fiber Action in the Cerebellar Cortex

    PubMed Central

    Cramer, Samuel W.; Gao, Wangcai; Chen, Gang

    2013-01-01

    The role of parallel fibers (PFs) in cerebellar physiology remains controversial. Early studies inspired the “beam” hypothesis whereby granule cell (GC) activation results in PF-driven, postsynaptic excitation of beams of Purkinje cells (PCs). However, the “radial” hypothesis postulates that the ascending limb of the GC axon provides the dominant input to PCs and generates patch-like responses. Using optical imaging and single-cell recordings in the mouse cerebellar cortex in vivo, this study reexamines the beam versus radial controversy. Electrical stimulation of mossy fibers (MFs) as well as microinjection of NMDA in the granular layer generates beam-like responses with a centrally located patch-like response. Remarkably, ipsilateral forepaw stimulation evokes a beam-like response in Crus I. Discrete molecular layer lesions demonstrate that PFs contribute to the peripherally generated responses in Crus I. In contrast, vibrissal stimulation induces patch-like activation of Crus II and GABAA antagonists fail to convert this patch-like activity into a beam-like response, implying that molecular layer inhibition does not prevent beam-like responses. However, blocking excitatory amino acid transporters (EAATs) generates beam-like responses in Crus II. These beam-like responses are suppressed by focal inhibition of MF-GC synaptic transmission. Using EAAT4 reporter transgenic mice, we show that peripherally evoked patch-like responses in Crus II are aligned between parasagittal bands of EAAT4. This is the first study to demonstrate beam-like responses in the cerebellar cortex to peripheral, MF, and GC stimulation in vivo. Furthermore, the spatial pattern of the responses depends on extracellular glutamate and its local regulation by EAATs. PMID:23843513

  1. Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation.

    PubMed

    Kishore, Asha; Popa, Traian; James, Praveen; Yahia-Cherif, Lydia; Backer, Febina; Varughese Chacko, Lijo; Govind, Preetha; Pradeep, Salini; Meunier, Sabine

    2014-11-01

    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.

  2. FoxP2 expression in the cerebellum and inferior olive: development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

    PubMed

    Fujita, Hirofumi; Sugihara, Izumi

    2012-02-15

    Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear.

  3. Temporal dynamics of cerebellar and motor cortex physiological processes during motor skill learning

    PubMed Central

    Spampinato, D.; Celnik, P.

    2017-01-01

    Learning motor tasks involves distinct physiological processes in the cerebellum (CB) and primary motor cortex (M1). Previous studies have shown that motor learning results in at least two important neurophysiological changes: modulation of cerebellar output mediated in-part by long-term depression of parallel fiber-Purkinje cell synapse and induction of long-term plasticity (LTP) in M1, leading to transient occlusion of additional LTP-like plasticity. However, little is known about the temporal dynamics of these two physiological mechanisms during motor skill learning. Here we use non-invasive brain stimulation to explore CB and M1 mechanisms during early and late motor skill learning in humans. We predicted that early skill acquisition would be proportional to cerebellar excitability (CBI) changes, whereas later stages of learning will result in M1 LTP-like plasticity modifications. We found that early, and not late into skill training, CBI changed. Whereas, occlusion of LTP-like plasticity over M1 occurred only during late, but not early training. These findings indicate a distinct temporal dissociation in the physiological role of the CB and M1 when learning a novel skill. Understanding the role and temporal dynamics of different brain regions during motor learning is critical to device optimal interventions to augment learning. PMID:28091578

  4. Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

    PubMed Central

    Valera, Antoine M; Binda, Francesca; Pawlowski, Sophie A; Dupont, Jean-Luc; Casella, Jean-François; Rothstein, Jeffrey D; Poulain, Bernard; Isope, Philippe

    2016-01-01

    Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex. DOI: http://dx.doi.org/10.7554/eLife.09862.001 PMID:26982219

  5. Age-related changes in rat cerebellar basket cells: a quantitative study using unbiased stereological methods

    PubMed Central

    HENRIQUE, RUI M. F.; ROCHA, EDUARDO; REIS, ALCINDA; MARCOS, RICARDO; OLIVEIRA, MARIA H.; SILVA, MARIA W.; MONTEIRO, ROGÉRIO A. F.

    2001-01-01

    Cortical cerebellar basket cells are stable postmitotic cells; hence, they are liable to endure age-related changes. Since the cerebellum is a vital organ for the postural control, equilibrium and motor coordination, we aimed to determine the quantitative morphological changes in those interneurons with the ageing process, using unbiased techniques. Material from the cerebellar cortex (Crus I and Crus II) was collected from female rats aged 2, 6, 9, 12, 15, 18, 21 and 24 mo (5 animals per each age group), fixed by intracardiac perfusion, and processed for transmission electron microscopy, using conventional techniques. Serial semithin sections were obtained (5 blocks from each rat), enabling the determination of the number-weighted mean nuclear volume (by the nucleator method). On ultrathin sections, 25 cell profiles from each animal were photographed. The volume density of the nucleus, ground substance, mitochondria, Golgi apparatus (Golgi) and dense bodies (DB), and the mean surface density of the rough endoplasmic reticulum (RER) were determined, by point counting, using a morphometric grid. The mean total volumes of the soma and organelles and the mean total surface area of the RER [s̄N (RER)] were then calculated. The results were analysed with 1-way ANOVA; posthoc pairwise comparisons of group means were performed using the Newman-Keuls test. The relation between age and each of the parameters was studied by regression analysis. Significant age-related changes were observed for the mean volumes of the soma, ground substance, Golgi, DB, and s̄N (RER). Positive linear trends were found for the mean volumes of the ground substance, Golgi, and DB; a negative linear trend was found for the s̄N (RER). These results indicate that rat cerebellar basket cells endure important age-related changes. The significant decrease in the s̄N (RER) may be responsible for a reduction in the rate of protein synthesis. Additionally, it may be implicated in a cascade of events

  6. An amplified promoter system for targeted expression of calcium indicator proteins in the cerebellar cortex

    PubMed Central

    Kuhn, Bernd; Ozden, Ilker; Lampi, Yulia; Hasan, Mazahir T.; Wang, Samuel S.-H.

    2012-01-01

    Recording of identified neuronal network activity using genetically encoded calcium indicators (GECIs) requires labeling that is cell type-specific and bright enough for the detection of functional signals. However, specificity and strong expression are often not achievable using the same promoter. Here we present a combinatorial approach for targeted expression and single-cell-level quantification in which a weak promoter is used to drive trans-amplification under a strong general promoter. We demonstrated this approach using recombinant adeno-associated viruses (rAAVs) to deliver the sequence of the GECI D3cpv in the mouse cerebellar cortex. Direct expression under the human synapsin promoter (hSYN) led to high levels of expression (50–100 μM) in five interneuron types of the cerebellar cortex but not in Purkinje cells (PCs) (≤10 μM), yielding sufficient contrast to allow functional signals to be recorded from somata and processes in awake animals using two-photon microscopy. When the hSYN promoter was used to drive expression of the tetracycline transactivator (tTA), a second rAAV containing the bidirectional TET promoter (Ptetbi) could drive strong D3cpv expression in PCs (10–300 μM), enough to allow reliable complex spike detection in the dendritic arbor. An amplified approach should be of use in monitoring neural processing in selected cell types and boosting expression of optogenetic probes. Additionally, we overcome cell toxicity associated with rAAV injection and/or local GECI overexpression by combining the virus injection with systemic pre-injection of hyperosmotic D-mannitol, and by this double the time window for functional imaging. PMID:22866030

  7. Hydroxyurea Treatment and Development of the Rat Cerebellum: Effects on the Neurogenetic Profiles and Settled Patterns of Purkinje Cells and Deep Cerebellar Nuclei Neurons.

    PubMed

    Martí, Joaquín; Santa-Cruz, M C; Serra, Roger; Hervás, José P

    2016-11-01

    The current paper analyzes the development of the male and female rat cerebellum exposed to hydroxyurea (HU) (300 or 600 mg/kg) as embryo and collected at postnatal day 90. Our study reveals that the administration of this drug compromises neither the cytoarchitecture of the cerebellar cortex nor deep nuclei (DCN). However, in comparison with the saline group, we observed that several cerebellar parameters were lower in the HU injected groups. These parameters included area of the cerebellum, cerebellar cortex length, molecular layer area, Purkinje cell number, granule cell counts, internal granular layer, white matter and cerebellar nuclei areas, and number of deep cerebellar nuclei neurons. These features were larger in the rats injected with saline, smaller in those exposed to 300 mg/kg of HU and smallest in the group receiving 600 mg/kg of this agent. No sex differences in the effect of the HU were observed. In addition, we infer the neurogenetic timetables and the neurogenetic gradients of PCs and DCN neurons in rats exposed to either saline or HU as embryos. For this purpose, 5-bromo-2'-deoxyuridine was injected into pregnant rats previously administered with saline or HU. This thymidine analog was administered following a progressively delayed cumulative labeling method. The data presented here show that systematic differences exist in the pattern of neurogenesis and in the spatial location of cerebellar neurons between rats injected with saline or HU. No sex differences in the effect of the HU were observed. These findings have implications for the administration of this compound to women in gestation as the effects of HU on the development of the cerebellum might persist throughout their offsprings' life.

  8. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  9. Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells

    PubMed Central

    Elisabetta Cesana, Lia Forti; Mapelli, Jonathan; D'Angelo, Egidio

    2006-01-01

    Although Golgi cells (GoCs), the main type of inhibitory interneuron in the cerebellar granular layer (GL), are thought to play a central role in cerebellar network function, their excitable properties have remained unexplored. GoCs fire rhythmically in vivo and in slices, but it was unclear whether this activity originated from pacemaker ionic mechanisms. We explored this issue in acute cerebellar slices from 3-week-old rats by combining loose cell-attached (LCA) and whole-cell (WC) recordings. GoCs displayed spontaneous firing at 1–10 Hz (room temperature) and 2–20 Hz (35–37°C), which persisted in the presence of blockers of fast synaptic receptors and mGluR and GABAB receptors, thus behaving, in our conditions, as pacemaker neurons. ZD 7288 (20 μm), a potent hyperpolarization-activated current (Ih) blocker, slowed down pacemaker frequency. The role of subthreshold Na+ currents (INa,sub) could not be tested directly, but we observed a robust TTX-sensitive, non-inactivating Na+ current in the subthreshold voltage range. When studying repolarizing currents, we found that retigabine (5 μm), an activator of KCNQ K+ channels generating neuronal M-type K+ (IM) currents, reduced GoC excitability in the threshold region. The KCNQ channel antagonist XE991 (5 μm) did not modify firing, suggesting that GoC IM has low XE991 sensitivity. Spike repolarization was followed by an after-hyperpolarization (AHP) supported by apamin-sensitive Ca2+-dependent K+ currents (Iapa). Block of Iapa decreased pacemaker precision without altering average frequency. We propose that feed-forward depolarization is sustained by Ih and INa,sub, and that delayed repolarizing feedback involves an IM-like current whose properties remain to be characterized. The multiple ionic mechanisms shown here to contribute to GoC pacemaking should provide the substrate for fine regulation of firing frequency and precision, thus influencing the cyclic inhibition exerted by GoCs onto the cerebellar GL

  10. The primary vestibular projection to the cerebellar cortex in the pigeon (Columba livia)

    SciTech Connect

    Schwarz, I.E.; Schwarz, D.W.

    1983-06-01

    The cerebellar cortex of the pigeon receiving direct vestibular afferents was delineated by anterograde transport of (/sup 3/H)-amino acids injected into the vestibular nerve. Labelled mossy fiber rosettes in the granular layer were concentrated in lobule X (nodulus) and to a lesser extent, in the ventral portion of lobule IXd (uvula and paraflocculus). A few solitary labelled rosettes were also found in more dorsal portions of lobule IX, as well as in the anterior lobe between lobule II and IV. The lingula remained unlabelled. Discrete injections of (/sup 3/H)-leucine into the cristae of each of the three semicircular canals or the utricular macula yielded a similar distribution of fewer labelled rosettes. A few primary mossy fiber terminals labelled after cochlear injections are attributed to afferents from the lagenar macula. Since effective diffusion of label from the injection site was excluded by controls, it is concluded that projection of individual canal and macula nerves to the vestibulocerebellar cortex is not topographically separated. It is proposed that this extensive convergence of various afferents is required by the cerebellum to compute precise and directionally specific control signals during head rotation in all conceivable planes.

  11. Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

    PubMed

    Mousa, Alyaa M; Al-Fadhli, Ameera S; Rao, Muddanna S; Kilarkaje, Narayana

    2015-01-01

    Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.

  12. Flavoprotein imaging in the cerebellar cortex in vivo: cellular and metabolic basis and insights into cerebellar function

    NASA Astrophysics Data System (ADS)

    Gao, Wangcai; Chen, Gang; Ebner, Timothy J.

    2009-02-01

    Flavoprotein autofluorescence is an activity dependent intrinsic signal. Flavoproteins are involved in the electron transport chain and change their fluorescence according to the cellular redox state. We have been using flavoprotein autofluorescence in the cerebellum to examine properties of cerebellar circuits. Studies have also focused on understanding the cellular and metabolic origins of this intrinsic optical signal. Parallel fiber stimulation evokes a beamlike response intersected by bands of decreased fluorescence. The beam response is biphasic, with an early fluorescence increase (light phase) followed by a slower decrease (dark phase). We show this signal originates from flavoproteins as determined by its wavelength selectivity and sensitivity to blockers of the electron transport chain. Selectively blocking glutamate receptors abolished the on-beam light phase with the dark phase remaining intact. This demonstrates that the light phase is due to postsynaptic neuronal activation and suggests the dark phase is primarily due to glial activation. The bands of reduced fluorescence intersecting the beam are primarily neuronal in origin, mediated by GABAergic transmission, and due to the inhibitory action of molecular layer interneurons on Purkinje cells and the interneurons themselves. This parasagittally organized molecular layer inhibition differentially modulates the spatial pattern of cerebellar cortical activity. Flavoprotein imaging also reveals the functional architectures underlying the responses to inferior olive and peripheral whisker pad stimulation. Therefore, flavoprotein autofluorescence imaging is providing new insights into cerebellar cortical function and neurometabolic coupling.

  13. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

    PubMed

    Zhang, Weiping; Schmelzeisen, Steffen; Parthier, Daniel; Frings, Stephan; Möhrlen, Frank

    2015-01-01

    Calcium-activated chloride channels of the anoctamin (alias TMEM16) protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

  14. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex

    PubMed Central

    Parthier, Daniel; Frings, Stephan; Möhrlen, Frank

    2015-01-01

    Calcium-activated chloride channels of the anoctamin (alias TMEM16) protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum. PMID:26558388

  15. Cellular and Metabolic Origins of Flavoprotein Autofluorescence in the Cerebellar Cortex in vivo

    PubMed Central

    Reinert, Kenneth C.; Gao, Wangcai; Chen, Gang; Wang, Xinming; Peng, Yu-Ping

    2013-01-01

    Flavoprotein autofluorescence imaging, an intrinsic mitochondrial signal, has proven useful for monitoring neuronal activity. In the cerebellar cortex, parallel fiber stimulation evokes a beam-like response consisting of an initial, short-duration increase in fluorescence (on-beam light phase) followed by a longer duration decrease (on-beam dark phase). Also evoked are parasagittal bands of decreased fluorescence due to molecular layer inhibition. Previous work suggests that the on-beam light phase is due to oxidative metabolism in neurons. The present study further investigated the metabolic and cellular origins of the flavoprotein signal in vivo, testing the hypotheses that the dark phase is mediated by glia activation and the inhibitory bands reflect decreased flavoprotein oxidation and increased glycolysis in neurons. Blocking postsynaptic ionotropic and metabotropic glutamate receptors abolished the onbeam light phase and the parasagittal bands without altering the on-beam dark phase. Adding glutamate transporter blockers reduced the dark phase. Replacing glucose with lactate (or pyruvate) or adding lactate to the bathing media abolished the on-beam dark phase and reduced the inhibitory bands without affecting the light phase. Blocking monocarboxylate transporters eliminated the on-beam dark phase and increased the light phase. These results confirm that the on-beam light phase is due primarily to increased oxidative metabolism in neurons. They also show that the on-beam dark phase involves activation of glycolysis in glia resulting in the generation of lactate that is transferred to neurons. Oxidative savings in neurons contributes to the decrease in fluorescence characterizing the inhibitory bands. These findings provide strong in vivo support for the astrocyte–neuron lactate shuttle hypothesis. PMID:21503591

  16. Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats

    PubMed Central

    Machado, Andre G.; Baker, Kenneth B.; Schuster, Daniel; Butler, Robert S.; Rezai, Ali

    2009-01-01

    Novel neurorehabilitative strategies are needed to improve motor outcomes following stroke. Based on the disynaptic excitatory projections of the dentatothalamocortical pathway to the motor cortex as well as anterior and posterior cortical areas, we hypothesize that chronic electrical stimulation of the contralesional dentate (lateral cerebellar) nucleus output can enhance motor recovery after ischemia via augmentation of perilesional cortical excitability. Seventy five Wistar rats were pre-trained in the Montoya staircase task and subsequently suffered left cerebral ischemia with the 3-vessel occlusion model. All survivors underwent stereotactic right lateral cerebellar nucleus (LCN) implantation of bipolar electrodes. Rats were then randomized to 4 groups: LCN stimulation at 10 pps, 20 pps, 50 pps or sham stimulation, which was delivered for a period of six weeks. Performance on the Montoya task was re-assessed over the last four weeks of the stimulation period. On the right (contralesional) side, motor performance of the groups undergoing sham, 10 pps, 20 pps and 50 pps stimulation was, respectively, 2.5± 2.7; 2.1 ± 2.5; 6.0 ± 3.9 (p<0.01) and 4.5 ± 3.5 pellets. There was no difference on the left (ipsilesional) side motor performance among the sham or stimulation groups, varying from 15.9 ± 6.7 to 17.2 ± 2.1 pellets. We conclude that contralesional chronic electrical stimulation of the lateral cerebellar nucleus at 20 pps but not at 10 or 50 pps improves motor recovery in rats following ischemic strokes. This effect is likely to be mediated by increased perilesional cortical excitability via chronic activation of the dentatothalamocortical pathway. PMID:19445910

  17. Effect of methotrexate on cerebellar development in infant rats.

    PubMed

    Sugiyama, Akihiko; Sun, Jing; Ueda, Kota; Furukawa, Satoshi; Takeuchi, Takashi

    2015-07-01

    Six-day-old rats were treated intraperitoneal injections with methotrexate 1 mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreased in the methotrexate-treated group instead of the control from 4 day after treatment (DAT) onward. A significant reduction in the width of the external granular layer was detected on 2 and 3 DAT in the methotrexate group. By 4 DAT, the width of the external granular layer of the methotrexate group was indistinguishable from the control, and by 8 DAT, it was greater than that of the control. The molecular layer of methotrexate group on 8 and 15 DAT was thinner than that of the control. On 1 DAT, in the methotrexate group, there were many TUNEL and cleaved caspase-3-positive granular cells throughout the external granular layer, and they decreased time-dependently. On 1 DAT, in the methotrexate group, phospho-histone H3-positive cells in the external granular layer were fewer than in the control and tended to increase on 2-4 DAT. The p21-positive-rate of the external granule cells in the MTX group was higher than in the control on 1-4 DAT. These results suggested that methotrexate exposure on postnatal day 6 induces a delay, slowing in the migration of external granular cells to the inner granular layer, attributed to decrease or inhibition in the production of external granular cells that had arisen from apoptosis and the decrease in cell proliferative activity, resulting in cerebellar hypoplasia.

  18. Electron Tomographic Structure and Protein Composition of Isolated Rat Cerebellar, Hippocampal and Cortical Postsynaptic Densities

    PubMed Central

    Farley, MM; Swulius, MT; Waxham, MN

    2015-01-01

    Electron tomography and immunogold labeling were used to analyze similarities and differences in the morphology and protein composition of postsynaptic densities (PSDs) isolated from adult rat cerebella, hippocampi, and cortices. There were similarities in physical dimensions and gross morphology between cortical, hippocampal and most cerebellar PSDs, although the morphology among cerebellar PSDs could be categorized into three distinct groups. The majority of cerebellar PSDs were composed of dense regions of protein, similar to cortical and hippocampal PSDs, while others were either composed of granular or latticelike protein regions. Significant differences were found in protein composition and organization across PSDs from the different brain regions. The signaling protein, βCaMKII, was found to be a major component of each PSD type and was more abundant than αCaMKII in both hippocampal and cerebellar PSDs. The scaffold molecule PSD-95, a major component of cortical PSDs, was found absent in a fraction of cerebellar PSDs and when present was clustered in its distribution. In contrast, immunogold labeling for the proteasome was significantly more abundant in cerebellar and hippocampal PSDs than cortical PSDs. Together, these results indicate that PSDs exhibit remarkable diversity in their composition and morphology, presumably as a reflection of the unique functional demands placed on different synapses. PMID:26215919

  19. Calcium-dependent chloride current in rat cerebellar Purkinje cell membranes.

    PubMed

    Vykhareva, E A; Zamoyski, V L; Grigoriev, V V; Bachurin, S O

    2015-01-01

    The presence of calcium-dependent potential-activated chloride currents in the membranes of freshly isolated rat cerebellar Purkinje cells (12-15 days) was shown by the whole-cell patch clamp technique. Chloride currents appeared in a sodium-free external solution and reversibly disappeared in the absence of external chloride and calcium ions.

  20. Protective Effect of PPARγ Agonists on Cerebellar Tissues Oxidative Damage in Hypothyroid Rats

    PubMed Central

    Baghcheghi, Yousef; Beheshti, Farimah; Salmani, Hossein; Soukhtanloo, Mohammad

    2016-01-01

    The aim of the current study was to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARγ) agonists on cerebellar tissues oxidative damage in hypothyroid rats. The animals included seven groups: group I (control), the animals received drinking water; group II, the animals received 0.05% propylthiouracil (PTU) in drinking water; besides PTU, the animals in groups III, IV, V, VI, and VII, were injected with 20 mg/kg vitamin E (Vit E), 10 or 20 mg/kg pioglitazone, and 2 or 4 mg/kg rosiglitazone, respectively. The animals were deeply anesthetized and the cerebellar tissues were removed for biochemical measurements. PTU administration reduced thiol content, superoxide dismutase (SOD), and catalase (CAT) activities in the cerebellar tissues while increasing malondialdehyde (MDA) and nitric oxide (NO) metabolites. Vit E, pioglitazone, and rosiglitazone increased thiol, SOD, and CAT in the cerebellar tissues while reducing MDA and NO metabolites. The results of present study showed that, similar to Vit E, both rosiglitazone and pioglitazone as PPARγ agonists exerted protective effects against cerebellar tissues oxidative damage in hypothyroid rats. PMID:28116157

  1. The Morpho/Functional Discrepancy in the Cerebellar Cortex: Looks Alone are Deceptive

    PubMed Central

    Rokni, Dan; Llinas, Rodolfo; Yarom, Yosef

    2008-01-01

    In a recent report we demonstrated that stimulation of cerebellar mossy fibers synchronously activates Purkinje cells that are located directly above the site of stimulation. We found that the activated Purkinje cells are arranged in a radial patch on the cerebellar surface and that this organization is independent of the integrity of the inhibitory system. This arrangement of activity is counterintuitive. The anatomical structure with the extensive parallel fiber system implies that mossy fiber stimulation will activate Purkinje cells along a beam of parallel fibers. In this short review we highlight this discrepancy between anatomical structure and functional dynamics and suggest a plausible underlying mechanism. PMID:19225592

  2. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes

  3. Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function.

    PubMed

    Naro, Antonino; Bramanti, Alessia; Leo, Antonino; Manuli, Alfredo; Sciarrone, Francesca; Russo, Margherita; Bramanti, Placido; Calabrò, Rocco Salvatore

    2017-01-07

    The cerebellum regulates several motor functions through two main mechanisms, the cerebellum-brain inhibition (CBI) and the motor surround inhibition (MSI). Although the exact cerebellar structures and functions involved in such processes are partially known, Purkinje cells (PC) and their surrounding interneuronal networks may play a pivotal role concerning CBI and MSI. Cerebellar transcranial alternating current stimulation (tACS) has been proven to shape specific cerebellar components in a feasible, safe, effective, and non-invasive manner. The aim of our study was to characterize the cerebellar structures and functions subtending CBI and MSI using a tACS approach. Fifteen healthy individuals underwent a cerebellar tACS protocol at 10, 50, and 300 Hz, or a sham-tACS over the right cerebellar hemisphere. We measured the tACS aftereffects on motor-evoked potential (MEP) amplitude, CBI induced by tACS (tiCBI) at different frequencies, MSI, and hand motor task performance. None of the participants had any side effect related to tACS. After 50-Hz tACS, we observed a clear tiCBI-50Hz weakening (about +30%, p < 0.001) paralleled by a MEP amplitude increase (about +30%, p = 0.001) and a reduction of the time required to complete some motor task (about -20%, p = 0.01), lasting up to 30 min. The 300-Hz tACS induced a selective, specific tiCBI-300Hz and tiCBI-50Hz modulation in surrounding muscles (about -15%, p = 0.01) and MSI potentiation (about +40%, p < 0.001). The 10-Hz tACS and the sham-tACS were ineffective (p > 0.6). Our preliminary data suggest that PC may represent the last mediator of tiCBI and that the surrounding interneuronal network may have an important role in updating MSI, tiCBI, and M1 excitability during tonic muscle contraction, by acting onto the PC. The knowledge of these neurophysiological issues offers new cues to design innovative, non-invasive neuromodulation protocols to shape cerebellar-cerebral functions.

  4. Cellular and Subcellular Localization of the RGS7/Gβ5/R7BP Complex in the Cerebellar Cortex

    PubMed Central

    Aguado, Carolina; Orlandi, Cesare; Fajardo-Serrano, Ana; Gil-Minguez, Mercedes; Martemyanov, Kirill A.; Luján, Rafael

    2016-01-01

    A member of regulator of G-protein signaling family, RGS7, is an essential modulator of signaling through GABAB receptors. RGS7 functions as a macromolecular complex with type 5 G protein β (Gβ5) and R7 binding protein (R7BP) to control the localization and function of the resultant heterotrimeric complexes. Here, we used co-immunoprecipitation, in situ hybridization, histoblot and immunohistochemical techniques at the light and electron microscopic level to advance understanding of RGS7-Gβ5-R7BP complexes in the central nervous system, focusing on distinct neuronal populations in the cerebellar cortex. Histoblot analysis showed that RGS7, Gβ5 and R7BP proteins were widely expressed in the brain, with mostly an overlapping pattern and showing a high expression level in the molecular layer of the cerebellar cortex. Co-immunoprecipitation experiments established that the RGS7/Gβ5 forms complexes with R7BP in the cerebellum. At the cellular level, RGS7 and R7BP mRNAs were expressed at the highest level in Purkinje cells (PCs) and Golgi cells, and at low levels in granule cells. Immunohistochemistry confirmed that labeling for RGS7, Gβ5 and R7BP were present in the three neuronal populations and concentrated in dendrites and spines. At the electron microscopic level, immunolabeling for RGS7, Gβ5 and R7BP proteins was found both at postsynaptic and presynaptic sites and showed similar distribution patterns. Immunoreactivity for the three proteins was mostly localized along the extrasynaptic plasma membrane of dendritic shafts and spines of PCs and to a lesser extent, in axon terminals (AT) establishing excitatory synapses. Quantitative analysis of immunogold particles for RGS7, Gβ5 and R7BP revealed that they are non-uniformly distributed along the surface of PCs, and show enrichment around excitatory synapses on dendritic spines. We further report that deletion of R7BP in mice reduced the targeting of both RGS7 and Gβ5 to the plasma membrane. Altogether, these

  5. Developmental regulation of glucose transporters GLUT3, GLUT4 and GLUT8 in the mouse cerebellar cortex

    PubMed Central

    Gómez, Olga; Ballester-Lurbe, Begoña; Poch, Enric; Mesonero, José E; Terrado, José

    2010-01-01

    Glucose uptake into the mammalian nervous system is mediated by the family of facilitative glucose transporter proteins (GLUT). In this work we investigate how the expression of the main neuronal glucose transporters (GLUT3, GLUT4 and GLUT8) is modified during cerebellar cortex maturation. Our results reveal that the levels of the three transporters increase during the postnatal development of the cerebellum. GLUT3 localizes in the growing molecular layer and in the internal granule cell layer. However, the external granule cell layer, Purkinje cell cytoplasm and cytoplasm of the other cerebellar cells lack GLUT3 expression. GLUT4 and GLUT8 have partially overlapping patterns, which are detected in the cytoplasm and dendrites of Purkinje cells, and also in the internal granule cell layer where GLUT8 displays a more diffuse pattern. The differential localization of the transporters suggests that they play different roles in the cerebellum, although GLUT4 and GLUT8 could also perform some compensatory or redundant functions. In addition, the increase in the levels and the area expressing the three transporters suggests that these roles become more important as development advances. Interestingly, the external granule cells, which have been shown to express the monocarboxylate transporter MCT2, express none of the three main neuronal GLUTs. However, when these cells migrate inwardly to differentiate in the internal granule cells, they begin to produce GLUT3, GLUT4 and GLUT8, suggesting that the maturation of the cerebellar granule cells involves a switch in their metabolism in such a way that they start using glucose as they mature. PMID:20819112

  6. Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

    PubMed

    Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

    2017-02-01

    Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

  7. Excitation of Rat Cerebellar Golgi Cells by Ethanol: Further Characterization of the Mechanism

    PubMed Central

    Botta, Paolo; de Souza, Fabio M. Simões; Sangrey, Thomas; De Schutter, Erik; Valenzuela, C. Fernando

    2012-01-01

    Background Studies with rodents suggest that acute ethanol exposure impairs information flow through the cerebellar cortex, in part, by increasing GABAergic input to granule cells. Experiments suggest that an increase in the excitability of specialized GABAergic interneurons that regulate granule cell activity (i.e. Golgi cells, GoCs) contributes to this effect. In GoCs, ethanol increases spontaneous action potential firing frequency, decreased the afterhyperpolarization amplitude, and depolarized the membrane potential. Studies suggest that these effects could be mediated by inhibition of the Na+/K+ ATPase. The purpose of this study was to characterize the potential role of other GoC conductances in the mechanism of action of ethanol. Methods Computer modeling techniques and patch-clamp electrophysiological recordings with acute slices from rat cerebella were used for these studies. Results Computer modeling suggested that modulation of subthreshold Na+ channels, hyperpolarization activated currents and several K+ conductances could explain some but not all actions of ethanol on GoCs. Electrophysiological studies did not find evidence consistent with a contribution of these conductances. Quinidine, a non-selective blocker of several types of channels (including several K+ channels) that also antagonizes the Na+/K+ ATPase, reduced the effect of ethanol on GoC firing. Conclusions These findings lend further support to the conclusion that ethanol increases GoC excitability via modulation of the Na+/K+ ATPase, and suggest that a quinidine-sensitive K+ channel may also play a role in the mechanism of action of ethanol. PMID:22004123

  8. Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex.

    PubMed

    Mansouri, Mahnaz; Kasugai, Yu; Fukazawa, Yugo; Bertaso, Federica; Raynaud, Fabrice; Perroy, Julie; Fagni, Laurent; Kaufmann, Walter A; Watanabe, Masahiko; Shigemoto, Ryuichi; Ferraguti, Francesco

    2015-01-01

    Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different forms of synaptic plasticity in the cerebellar cortex, e.g. long-term depression at glutamatergic synapses and rebound potentiation at GABAergic synapses. These various forms of plasticity might depend on the subsynaptic arrangement of the receptor in Purkinje cells that can be regulated by protein-protein interactions. This study investigated, by means of the freeze-fracture replica immunogold labelling method, the subcellular localization of mGlu1 receptors in the rodent cerebellum and whether Homer proteins regulate their subsynaptic distribution. We observed a widespread extrasynaptic localization of mGlu1 receptors and confirmed their peri-synaptic enrichment at glutamatergic synapses. Conversely, we detected mGlu1 receptors within the main body of GABAergic synapses onto Purkinje cell dendrites. Although Homer proteins are known to interact with the mGlu1 receptor C-terminus, we could not detect Homer3, the most abundant Homer protein in the cerebellar cortex, at GABAergic synapses by pre-embedding and post-embedding immunoelectron microscopy. We then hypothesized a critical role for Homer proteins in the peri-junctional localization of mGlu1 receptors at glutamatergic synapses. To disrupt Homer-associated protein complexes, mice were tail-vein injected with the membrane-permeable dominant-negative TAT-Homer1a. Freeze-fracture replica immunogold labelling analysis showed no significant alteration in the mGlu1 receptor distribution pattern at parallel fibre-Purkinje cell synapses, suggesting that other scaffolding proteins are involved in the peri-synaptic confinement. The identification of interactors that regulate the subsynaptic localization of the mGlu1 receptor at neurochemically distinct synapses may offer new insight into its trafficking and intracellular signalling.

  9. Effects of prenatal paraquat and mancozeb exposure on amino acid synaptic transmission in developing mouse cerebellar cortex.

    PubMed

    Miranda-Contreras, Leticia; Dávila-Ovalles, Rosaura; Benítez-Díaz, Pedro; Peña-Contreras, Zulma; Palacios-Prü, Ernesto

    2005-11-07

    The goal of this study was to analyze the effects of prenatal exposure to the pesticides paraquat (PQ) and mancozeb (MZ) on the development of synaptic transmission in mouse cerebellar cortex. Pregnant NMRI mice were treated with either saline, 10 mg/kg PQ, 30 mg/kg MZ or the combination of PQ + MZ, between gestational days 12 (E12) and E20. Variation in the levels of amino acid neurotransmitters was determined by HPLC, between postnatal day 1 (P1) and P30. Motor coordination was assessed by locomotor activity evaluation of control and experimental pups at P14, P21 and P30. Significant reductions in the levels of excitatory neurotransmitters, aspartate and glutamate, were observed in PQ-, MZ- or combined PQ + MZ-exposed pups, with respect to control, during peak periods of excitatory innervation of Purkinje cells: between P2-P5 and P11-P15. However, at P30, lower aspartate contents, in contrast with increased glutamate levels, were detected in all experimental groups. During the first two postnatal weeks, delays in GABA and glycine ontogenesis were observed in PQ- and PQ + MZ-exposed pups, whereas notable decrements in GABA and glycine levels were seen in PQ + MZ-exposed animals. Decreased taurine contents were detected at P3 and P11 in PQ- and PQ + MZ-exposed mice. Pups in different experimental groups all showed hyperactivity at P14 and then exhibited reduced locomotor activity at P30. Taken together, our results indicate that prenatal exposure to either PQ or MZ or the combination of both could alter the chronology and magnitude of synaptic transmission in developing mouse cerebellar cortex.

  10. Low in situ expression of antioxidative enzymes in rat cerebellar granular cells susceptible to methylmercury.

    PubMed

    Fujimura, M; Usuki, F

    2014-01-01

    Methylmercury (MeHg), an environmental neurotoxicant, induces site-specific toxicity in the brain. Although oxidative stress has been demonstrated with MeHg toxicity, the site-specific toxicity is not completely understood. Among the cerebellar neurons, cerebellar granule cells (CGCs) appear vulnerable to MeHg, whereas Purkinje cells and molecular layer neurons are resistant. Here, we use a MeHg-intoxicated rat model to investigate these cerebellar neurons for the different causes of susceptibility to MeHg. Rats were exposed to 20 ppm MeHg for 4 weeks and subsequently exhibited neuropathological changes in the cerebellum that were similar to those observed in humans. We first isolated the three cerebellar neuron types using a microdissection system and then performed real-time PCR analyses for antioxidative enzymes. We observed that expression of manganese-superoxide dismutase (Mn-SOD), glutathione peroxidase 1 (GPx1), and thioredoxin reductase 1 (TRxR1) was significantly higher in Purkinje cells and molecular layer neurons than in CGCs. Finally, we performed immunohistochemical analyses on the cerebellum. Immunohistochemistry showed increased expression of Mn-SOD, GPx1, and TRxR1 in Purkinje cells and molecular layer neurons, which was coincident with the mRNA expression patterns. Considering Mn-SOD, GPx1, and TRxR1 are critical for protecting cells against MeHg intoxication, the results indicate that low expression of these antioxidative enzymes increases CGCs vulnerability to MeHg toxicity.

  11. Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

    PubMed Central

    Wang, Tsui-chin; Ngampramuan, Sukonthar; Kotchabhakdi, Naiphinich

    2016-01-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements. The exaggerated movements have been studied and have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has also been identified as the possible target of dystonia, in the search for alternative treatments. Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced, cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected and sham-operated groups. Beam walking apparatus, telemetric electromyography (EMG) recording, and histological verification were performed to confirm dystonic symptoms in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were scored based on motor amelioration assessed via beam walking. The result of this study suggests and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral assessment through beam walking, tiagabine is demonstrated as being effective in reducing dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia. PMID:28337103

  12. The treasury of the commons: making use of public gene expression resources to better characterize the molecular diversity of inhibitory interneurons in the cerebellar cortex.

    PubMed

    Schilling, Karl; Oberdick, John

    2009-12-01

    We mined the Allen Mouse Brain Atlas for genes expressed in cerebellar cortical inhibitory interneurons that would allow identification and possibly distinction of these cells. We identified some 90 genes that are highly expressed in specific subsets of cerebellar cortical inhibitory interneurons or various combinations thereof. Four genes are exclusively expressed, within the cerebellar cortex, in molecular layer interneurons, and ten genes label exclusively inhibitory interneurons in the granule cell layer or subsets thereof. Differential expression of many of these genes in cells residing in the lower versus the upper molecular layer provides evidence that these cells, traditionally referred to as basket and stellate cells, are indeed molecularly distinct. Two genes could be identified as novel markers for unipolar brush cells. Intersection of these data with embryonic expression patterns as documented in the genepaint repository does not support a hierarchical model of cerebellar interneuron development, but may be more easily reconciled with the view that cerebellar inhibitory interneurons derive from a common precursor pool from which they are specified only late into their development. The novel markers identified here should prove useful for probing the timing and mechanisms supporting cerebellar cortical interneuron specification and diversification.

  13. Compartmentation of the cerebellar cortex: adaptation to lifestyle in the star-nosed mole Condylura cristata.

    PubMed

    Marzban, Hassan; Hoy, Nathan; Buchok, Matthew; Catania, Kenneth C; Hawkes, Richard

    2015-04-01

    The adult mammalian cerebellum is histologically uniform. However, concealed beneath the simple laminar architecture, it is organized rostrocaudally and mediolaterally into complex arrays of transverse zones and parasagittal stripes that is both highly reproducible between individuals and generally conserved across mammals and birds. Beyond this conservation, the general architecture appears to be adapted to the animal's way of life. To test this hypothesis, we have examined cerebellar compartmentation in the talpid star-nosed mole Condylura cristata. The star-nosed mole leads a subterranean life. It is largely blind and instead uses an array of fleshy appendages (the "star") to navigate and locate its prey. The hypothesis suggests that cerebellar architecture would be modified to reduce regions receiving visual input and expand those that receive trigeminal afferents from the star. Zebrin II and phospholipase Cß4 (PLCß4) immunocytochemistry was used to map the zone-and-stripe architecture of the cerebellum of the adult star-nosed mole. The general zone-and-stripe architecture characteristic of all mammals is present in the star-nosed mole. In the vermis, the four typical transverse zones are present, two with alternating zebrin II/PLCß4 stripes, two wholly zebrin II+/PLCß4-. However, the central and nodular zones (prominent visual receiving areas) are proportionally reduced in size and conversely, the trigeminal-receiving areas (the posterior zone of the vermis and crus I/II of the hemispheres) are uncharacteristically large. We therefore conclude that cerebellar architecture is generally conserved across the Mammalia but adapted to the specific lifestyle of the species.

  14. Gamma oscillations in the somatosensory cortex of newborn rats.

    PubMed

    Gerasimova, E V; Zakharov, A V; Lebedeva, Yu A; Inacio, A R; Minlebaev, M G; Sitdikova, G F; Khazipov, R N

    2014-01-01

    Here we addressed a question of whether gamma oscillations previously described in the whisker-related barrel cortex are a universal pattern of activity in the somatosensory cortex of newborn rats. Intracortical recording of local field potentials and action potentials in neurons using multisite silicon electrodes in 2-7-day-old rats showed that mechanical stimulation of single fingers or specific areas on the plantar or back side of the foot evoked early gamma oscillations followed by spindle-burst oscillations in the corresponding regions of the somatosensory cortex. Early gamma oscillations had maximum amplitude in layer IV of the somatosensory cortex and effectively synchronized action potentials in layer IV neurons. It was concluded that early gamma oscillations evoked by activation of the topographic sensory input are a universal activity pattern of the entire somatosensory cortex of newborn rats.

  15. Age-Related Changes in Processing Speed: Unique Contributions of Cerebellar and Prefrontal Cortex

    PubMed Central

    Eckert, Mark A.; Keren, Noam I.; Roberts, Donna R.; Calhoun, Vince D.; Harris, Kelly C.

    2010-01-01

    Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology. PMID:20300463

  16. Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro.

    PubMed

    Yu, Lei; Zhang, Xiao-Yang; Zhang, Jun; Zhu, Jing-Ning; Wang, Jian-Jun

    2010-03-01

    Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep-wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM-1 microM) or orexin B (100 nM-1 microM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca(2+)/high-Mg(2+) medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala(11), D-Leu(15)] orexin B, a highly selective orexin 2 receptor (OX(2)R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX(2)R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.

  17. Cerebellar and Prefrontal Cortex Contributions to Adaptation, Strategies, and Reinforcement Learning

    PubMed Central

    Taylor, Jordan A.; Ivry, Richard B.

    2014-01-01

    Traditionally, motor learning has been studied as an implicit learning process, one in which movement errors are used to improve performance in a continuous, gradual manner. The cerebellum figures prominently in this literature given well-established ideas about the role of this system in error-based learning and the production of automatized skills. Recent developments have brought into focus the relevance of multiple learning mechanisms for sensorimotor learning. These include processes involving repetition, reinforcement learning, and strategy utilization. We examine these developments, considering their implications for understanding cerebellar function and how this structure interacts with other neural systems to support motor learning. Converging lines of evidence from behavioral, computational, and neuropsychological studies suggest a fundamental distinction between processes that use error information to improve action execution or action selection. While the cerebellum is clearly linked to the former, its role in the latter remains an open question. PMID:24916295

  18. Cerebellar and prefrontal cortex contributions to adaptation, strategies, and reinforcement learning.

    PubMed

    Taylor, Jordan A; Ivry, Richard B

    2014-01-01

    Traditionally, motor learning has been studied as an implicit learning process, one in which movement errors are used to improve performance in a continuous, gradual manner. The cerebellum figures prominently in this literature given well-established ideas about the role of this system in error-based learning and the production of automatized skills. Recent developments have brought into focus the relevance of multiple learning mechanisms for sensorimotor learning. These include processes involving repetition, reinforcement learning, and strategy utilization. We examine these developments, considering their implications for understanding cerebellar function and how this structure interacts with other neural systems to support motor learning. Converging lines of evidence from behavioral, computational, and neuropsychological studies suggest a fundamental distinction between processes that use error information to improve action execution or action selection. While the cerebellum is clearly linked to the former, its role in the latter remains an open question.

  19. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Li, G.-H.; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum [Exp. Biol. Med. 226 (2000) 790]. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion moiecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum.

  20. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

    NASA Technical Reports Server (NTRS)

    Nguon, K.; Li, G-H; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion molecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  1. Sensory Stimulation-Dependent Plasticity in the Cerebellar Cortex of Alert Mice

    PubMed Central

    Márquez-Ruiz, Javier; Cheron, Guy

    2012-01-01

    In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum. PMID:22563448

  2. The retrosplenial cortex and object recency memory in the rat.

    PubMed

    Powell, Anna L; Vann, Seralynne D; Olarte-Sánchez, Cristian M; Kinnavane, Lisa; Davies, Moira; Amin, Eman; Aggleton, John P; Nelson, Andrew J D

    2017-04-10

    It has been proposed that the retrosplenial cortex forms part of a "where/when" information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to "what/when" information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c-fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c-fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c-fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c-fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon, and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information. This article is protected by copyright. All rights reserved.

  3. Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats.

    PubMed

    Pañeda, Covadonga; Arroba, Ana I; Frago, Laura M; Holm, Anne Mette; Rømer, John; Argente, Jesús; Chowen, Julie A

    2003-08-26

    Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

  4. Crossed Cerebellar Atrophy of the Lateral Cerebellar Nucleus in an Endothelin-1-Induced, Rodent Model of Ischemic Stroke

    PubMed Central

    Chan, Hugh H.; Cooperrider, Jessica L.; Park, Hyun-Joo; Wathen, Connor A.; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is a functional deficit of the cerebellar hemisphere resulting from loss of afferent input consequent to a lesion of the contralateral cerebral hemisphere. It is manifested as a reduction of metabolism and blood flow and, depending on severity and duration, it can result in atrophy, a phenomenon known as crossed cerebellar atrophy (CCA). While CCA has been well-demonstrated in humans, it remains poorly characterized in animal models of stroke. In this study we evaluated the effects of cerebral cortical ischemia on contralateral cerebellar anatomy using an established rodent model of chronic stroke. The effects of cortical ischemia on the cerebellar hemispheres, vermis and deep nuclei were characterized. Intracortical microinjections of endothelin-1 (ET-1) were delivered to the motor cortex of Long Evans rats to induce ischemic stroke, with animals sacrificed 6 weeks later. Naive animals served as controls. Cerebral sections and cerebellar sections including the deep nuclei were prepared for analysis with Nissl staining. Cortical ischemia was associated with significant thickness reduction of the molecular layer at the Crus 1 and parafloccular lobule (PFL), but not in fourth cerebellar lobule (4Cb), as compared to the ipsilesional cerebellar hemisphere. A significant reduction in volume and cell density of the lateral cerebellar nucleus (LCN), the rodent correlate of the dentate nucleus, was also noted. The results highlight the relevance of corticopontocerebellar (CPC) projections for cerebellar metabolism and function, including its direct projections to the LCN. PMID:28261086

  5. In vivo imaging of neural reactive plasticity after laser axotomy in cerebellar cortex

    NASA Astrophysics Data System (ADS)

    Allegra Mascaro, A. L.; Sacconi, L.; Maco, B.; Knott, G. W.; Pavone, F. S.

    2014-03-01

    Multi-photon imaging provides valuable insights into the continuous reshaping of neuronal connectivity in live brain. We previously showed that single neuron or even single spine ablation can be achieved by laser-mediated dissection. Furthermore, single axonal branches can be dissected avoiding collateral damage to the adjacent dendrite and the formation of a persistent glial scar. Here, we describe the procedure to address the structural plasticity of cerebellar climbing fibers by combining two-photon in vivo imaging with laser axotomy in a mouse model. This method is a powerful tool to study the basic mechanisms of axonal rewiring after single branch axotomy in vivo. In fact, despite the denervated area being very small, the injured axons consistently reshape the connectivity with surrounding neurons, as indicated by the increase in the turnover of synaptic boutons. In addition, time-lapse imaging reveals the sprouting of new branches from the injured axon. Newly formed branches with varicosities suggest the possible formation of synaptic contacts. Correlative light and electron microscopy revealed that the sprouted branch contains large numbers of vesicles, with varicosities in the close vicinity of Purkinje dendrites.

  6. Role of the cerebellar cortex in conditioned goal-directed behavior.

    PubMed

    Burguière, Eric; Arabo, Arnaud; Jarlier, Frederic; De Zeeuw, Chris I; Rondi-Reig, Laure

    2010-10-06

    Learning a new goal-directed behavioral task often requires the improvement of at least two processes, including an enhanced stimulus-response association and an optimization of the execution of the motor response. The cerebellum has recently been shown to play a role in acquiring goal-directed behavior, but it is unclear to what extent it contributes to a change in the stimulus-response association and/or the optimization of the execution of the motor response. We therefore designed the stimulus-dependent water Y-maze conditioning task, which allows discrimination between both processes, and we subsequently subjected Purkinje cell-specific mutant mice to this new task. The mouse mutants L7-PKCi, which suffer from impaired PKC-dependent processes such as parallel fiber to Purkinje cell long-term depression (PF-PC LTD), were able to acquire the stimulus-response association, but exhibited a reduced optimization of their motor performance. These data show that PF-PC LTD is not required for learning a stimulus-response association, but they do suggest that a PKC-dependent process in cerebellar Purkinje cells is required for optimization of motor responses.

  7. Projection from the perirhinal cortex to the frontal motor cortex in the rat.

    PubMed

    Kyuhou, Shin ichi; Gemba, Hisae

    2002-03-01

    Stimulation of the anterior perirhinal cortex (PERa) induced marked surface-negative and depth-positive field potentials in the rat frontal motor cortex (MC) including the rostral and caudal forelimb areas. Injection of biotinylated dextran into the PERa densely labeled axon terminals in the superficial layers of the MC, where vigorous unit responses were evoked after PERa stimulation, indicated that the perirhinal-frontal projection preferentially activates the superficial layer neurons of the MC.

  8. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    PubMed

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  9. Differential effects of primary motor cortex and cerebellar transcranial direct current stimulation on motor learning in healthy individuals: A randomized double-blind sham-controlled study.

    PubMed

    Ehsani, F; Bakhtiary, A H; Jaberzadeh, S; Talimkhani, A; Hajihasani, A

    2016-11-01

    The purpose of study was to compare the effect of primary motor cortex (M1) and cerebellar anodal transcranial direct current stimulation (a-tDCS) on online and offline motor learning in healthy individuals. Fifty-nine healthy volunteers were randomly divided into three groups (n=20 in two experimental groups and n=19 in sham-control group). One experimental group received M1a-tDCSand another received cerebellar a-tDCS. The main outcome measure were response time (RT) and number of errors during serial response time test (SRTT) which were assessed prior, 35min and 48h after the interventions. Reduction of response time (RT) and error numbers at last block of the test compared to the first block was considered online learning. Comparison of assessments during retention tests was considered as short-term and long-term offline learning. Online RT reduction was not different among groups (P>0.05), while online error reduction was significantly greater in cerebellar a-tDCS than sham-control group (P<0.017). Moreover, a-tDCS on both M1 and cerebellar regions produced more long-term offline learning as compared to sham tDCS (P<0.01), while short-term offline RT reduction was significantly greater in M1a-tDCS than sham-control group (P<0.05). The findings indicated that although cerebellar a-tDCS enhances online learning and M1a-tDCS has more effect on short-term offline learning, both M1 and cerebellar a-tDCS can be used as a boosting technique for improvement of offline motor learning in healthy individuals.

  10. Cerebellar cortex granular layer interneurons in the macaque monkey are functionally driven by mossy fiber pathways through net excitation or inhibition.

    PubMed

    Laurens, Jean; Heiney, Shane A; Kim, Gyutae; Blazquez, Pablo M

    2013-01-01

    The granular layer is the input layer of the cerebellar cortex. It receives information through mossy fibers, which contact local granular layer interneurons (GLIs) and granular layer output neurons (granule cells). GLIs provide one of the first signal processing stages in the cerebellar cortex by exciting or inhibiting granule cells. Despite the importance of this early processing stage for later cerebellar computations, the responses of GLIs and the functional connections of mossy fibers with GLIs in awake animals are poorly understood. Here, we recorded GLIs and mossy fibers in the macaque ventral-paraflocculus (VPFL) during oculomotor tasks, providing the first full inventory of GLI responses in the VPFL of awake primates. We found that while mossy fiber responses are characterized by a linear monotonic relationship between firing rate and eye position, GLIs show complex response profiles characterized by "eye position fields" and single or double directional tunings. For the majority of GLIs, prominent features of their responses can be explained by assuming that a single GLI receives inputs from mossy fibers with similar or opposite directional preferences, and that these mossy fiber inputs influence GLI discharge through net excitatory or inhibitory pathways. Importantly, GLIs receiving mossy fiber inputs through these putative excitatory and inhibitory pathways show different firing properties, suggesting that they indeed correspond to two distinct classes of interneurons. We propose a new interpretation of the information flow through the cerebellar cortex granular layer, in which mossy fiber input patterns drive the responses of GLIs not only through excitatory but also through net inhibitory pathways, and that excited and inhibited GLIs can be identified based on their responses and their intrinsic properties.

  11. Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

    PubMed

    Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

    2016-06-01

    The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

  12. Peripheral Nerve Injury in Developing Rats Reorganizes Motor Cortex.

    DTIC Science & Technology

    1986-05-19

    Island 02912 *r201-484 It. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Personnel and Training Research Program May 19, 1986 Office of Naval...The Cerebral Cortex The Functional Areas of the Cerebral Cortex, E. G. Jones and A. Peters. Eds. (Plenum, New York, 1986 ) vol. 5, p. 243-270. 12. In rat...and processed for Nissl substance or cytochrome oxidase staining. In reconstructions, nap borders were defined as the mid-point between two distinct

  13. Model-Founded Explorations of the Roles of Molecular Layer Inhibition in Regulating Purkinje Cell Responses in Cerebellar Cortex: More Trouble for the Beam Hypothesis

    PubMed Central

    Bower, James M.

    2010-01-01

    For most of the last 50 years, the functional interpretation for inhibition in cerebellar cortical circuitry has been dominated by the relatively simple notion that excitatory and inhibitory dendritic inputs sum, and if that sum crosses threshold at the soma the Purkinje cell generates an action potential. Thus, inhibition has traditionally been relegated to a role of sculpting, restricting, or blocking excitation. At the level of networks, this relatively simply notion is manifest in mechanisms like “surround inhibition” which is purported to “shape” or “tune” excitatory neuronal responses. In the cerebellum, where all cell types except one (the granule cell) are inhibitory, these assumptions regarding the role of inhibition continue to dominate. Based on our recent series of modeling and experimental studies, we now suspect that inhibition may play a much more complex, subtle, and central role in the physiological and functional organization of cerebellar cortex. This paper outlines how model-based studies are changing our thinking about the role of feed-forward molecular layer inhibition in the cerebellar cortex. The results not only have important implications for continuing efforts to understand what the cerebellum computes, but might also reveal important features of the evolution of this large and quintessentially vertebrate brain structure. PMID:20877427

  14. Dorsomedial prefrontal cortex and cerebellar contribution to in-group attitudes: a transcranial magnetic stimulation study.

    PubMed

    Gamond, Lucile; Ferrari, Chiara; La Rocca, Stefania; Cattaneo, Zaira

    2017-04-01

    We tend to express more positive judgments and behaviors toward individuals belonging to our own group compared to other (out-) groups. In this study, we assessed the role of the cerebellum and of the dorsomedial prefrontal cortex (dmPFC) - two regions critically implicated in social cognition processes - in mediating implicit valenced attitudes toward in-group and out-group individuals. To this aim, we used transcranial magnetic stimulation (TMS) in combination with a standard attitude priming task, in which Caucasian participants had to categorize the valence of a series of adjectives primed by either an in-group or an out-group face. In two behavioral experiments, we found an in-group bias (i.e. faster categorization of positive adjectives when preceded by in-group faces) but no evidence of an out-group bias. Interestingly, TMS over both the dmPFC and over the (right) cerebellum significantly interfered with the modulation exerted by group membership on adjective valence classification, abolishing the in-group bias observed at baseline. Overall, our data suggest that both the dmPFC and the cerebellum play a causal role in mediating implicit social attitudes.

  15. Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

    PubMed Central

    Goji, Aya; Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji

    2017-01-01

    Purpose Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Methods Study participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. Results In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. Conclusion The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls. PMID:28060873

  16. Cerebellar secretin modulates eyeblink classical conditioning

    PubMed Central

    Fuchs, Jason R.; Robinson, Gain M.; Dean, Aaron M.; Schoenberg, Heidi E.; Williams, Michael R.; Morielli, Anthony D.

    2014-01-01

    We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received intracerebellar infusions of the secretin receptor antagonist 5-27 secretin or vehicle into the lobulus simplex of cerebellar cortex immediately prior to sessions 1–3 of acquisition. Antagonist-infused rats showed a reduction in the percentage of eyeblink CRs compared with vehicle-infused rats. In Experiment 2, rats received intracerebellar infusions of secretin or vehicle immediately prior to sessions 1–2 of extinction. Secretin did not significantly affect extinction performance. In Experiment 3, rats received intracerebellar infusions of 5-27 secretin or vehicle immediately prior to sessions 1–2 of extinction. The secretin antagonist did not significantly affect extinction performance. Together, our current and previous results indicate that both exogenous and endogenous cerebellar secretin modulate acquisition, but not extinction, of EBC. We have previously shown that (1) secretin reduces surface expression of the voltage-gated potassium channel α-subunit Kv1.2 in cerebellar cortex and (2) intracerebellar infusions of a Kv1.2 blocker enhance EBC acquisition, much like secretin. Kv1.2 is almost exclusively expressed in cerebellar cortex at basket cell–Purkinje cell pinceaus and Purkinje cell dendrites; we propose that EBC-induced secretin release from PCs modulates EBC acquisition by reducing surface expression of Kv1.2 at one or both of these sites. PMID:25403455

  17. Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats.

    PubMed

    Qiao, Xiao; Yang, Jun; Fei, Su-Juan; Zhu, Jin-Zhou; Zhu, Sheng-Ping; Liu, Zhang-Bo; Li, Ting-Ting; Zhang, Jian-Fu

    2015-12-10

    In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.

  18. Clumsiness and disturbed cerebellar development: insights from animal experiments.

    PubMed

    Gramsbergen, Albert

    2003-01-01

    Cerebellar functioning has been implied in the fine adjustments of muscle tone, in the coordination and the feed-forward control of movements and posture, as well as in the establishment and performance of motor skills. The cerebellar cortex in mammals develops late in neuro-ontogeny and an extrapolation from experimental results indicates that in the human the proliferation of the granule cells and the development of circuitry in the cerebellar cortex starts only in the last trimester of pregnancy and lasts until beyond the first birthday. This late development makes the cerebellar development particularly vulnerable to situations like an insufficient supply of nutrients, which may follow placental dysfunction, or to side effects of pharmacological treatments like the administration of corticosteroids in the postnatal period. We studied whether such situations might also lead to motor impairments. In rats, the effects of undernutrition during the brain growth spurt were investigated as well as those of corticosteroids administered in a period that is analogous to the 7th to 8th month of pregnancy in the human. Both these interferences affect cerebellar development and our results in rats indicate that they also lead to retardations in the emergence of certain reflexes, as well as to longer lasting motor impairments during locomotion. Extrapolation of these results strongly suggests that a disturbed cerebellar development should be considered as an important etiological factor in clumsiness in human children.

  19. Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats

    PubMed Central

    2016-01-01

    Cerebellar function is critical for coordinating movement and motor learning. However, events occurring in the cerebellum following spinal cord injury (SCI) have not been investigated in detail. We provide evidence of SCI-induced cerebellar synaptic changes involving a loss of granule cell parallel fiber input to distal regions of the Purkinje cell dendritic tree. This is accompanied by an apparent increase in synaptic contacts to Purkinje cell proximal dendrites, presumably from climbing fibers originating in the inferior olive. We also observed an early stage injury-induced decrease in the levels of cerebellin-1, a synaptic organizing molecule that is critical for establishing and maintaining parallel fiber-Purkinje cell synaptic integrity. Interestingly, this transsynaptic reorganizational pattern is consistent with that reported during development and in certain transgenic mouse models. To our knowledge, such a reorganizational event has not been described in response to SCI in adult rats. Regardless, the novel results of this study are important for understanding SCI-induced synaptic changes in the cerebellum, which may prove critical for strategies focusing on promoting functional recovery. PMID:27504204

  20. Decoding bipedal locomotion from the rat sensorimotor cortex

    NASA Astrophysics Data System (ADS)

    Rigosa, J.; Panarese, A.; Dominici, N.; Friedli, L.; van den Brand, R.; Carpaneto, J.; DiGiovanna, J.; Courtine, G.; Micera, S.

    2015-10-01

    Objective. Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Approach. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. Main results. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Significance. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds

  1. A light and electron microscope study of rat abducens nucleus neurons projecting to the cerebellar flocculus.

    PubMed Central

    Rodella, L; Rezzani, R; Corsetti, G; Simonetti, C; Stacchiotti, A; Ventura, R G

    1995-01-01

    Injection of horseradish peroxidase (HRP) into the cerebellar flocculus of the rat was employed to identify neurons in the abducens nucleus that project to the flocculus. The number, ultrastructural features and precise localisation of these neurons in the nucleus were examined. They were present bilaterally and represented about 7% of the total neuronal population of each nucleus. They were localised principally in the dorsomedial area of the cranial half of each nucleus and did not display the typical ultrastructural features of motoneurons. It is concluded that the localisation and ultrastructural characteristics of these HRP-positive neurons are useful for distinguishing them from other neuronal populations within the nucleus. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:7649835

  2. Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

    PubMed

    Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

    2016-05-01

    Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells.

  3. Hippocampal and Cerebellar Single-Unit Activity During Delay and Trace Eyeblink Conditioning in the Rat

    PubMed Central

    Green, John T.; Arenos, Jeremy D.

    2007-01-01

    In delay eyeblink conditioning, the CS overlaps with the US and only a brainstem-cerebellar circuit is necessary for learning. In trace eyeblink conditioning, the CS ends before the US is delivered and several forebrain structures, including the hippocampus, are required for learning, in addition to a brainstem-cerebellar circuit. The interstimulus interval (ISI) between CS onset and US onset is perhaps the most important factor in classical conditioning, but studies comparing delay and trace conditioning have typically not matched these procedures in this crucial factor, so it is often difficult to determine whether results are due to differences between delay and trace or to differences in ISI. In the current study, we employed a 580-ms CS-US interval for both delay and trace conditioning and compared hippocampal CA1 activity and cerebellar interpositus nucleus activity in order to determine whether a unique signature of trace conditioning exists in patterns of single-unit activity in either structure. Long-Evans rats were chronically implanted in either CA1 or interpositus with microwire electrodes and underwent either delay eyeblink conditioning, or trace eyeblink conditioning with a 300-ms trace period between CS offset and US onset. On trials with a CR in delay conditioning, CA1 pyramidal cells showed increases in activation (relative to a pre-CS baseline) during the CS-US period in sessions 1-4 that was attenuated by sessions 5-6. In contrast, on trials with a CR in trace conditioning, CA1 pyramidal cells did not show increases in activation during the CS-US period until sessions 5-6. In sessions 5-6, increases in activation were present only to the CS and not during the trace period. For rats with interpositus electrodes, activation of interpositus neurons on CR trials was present in all sessions in both delay and trace conditioning. However, activation was greater in trace compared to delay conditioning in the first half of the CS-US interval (during the

  4. Tactile responses in the granule cell layer of cerebellar folium crus IIa of freely behaving rats

    NASA Technical Reports Server (NTRS)

    Hartmann, M. J.; Bower, J. M.

    2001-01-01

    We recorded activity from the granule cell layer (GCL) of cerebellar folium Crus IIa as freely moving rats engaged in a variety of natural behaviors, including grooming, eating, and free tactile exploration. Multiunit responses in the 1000-4500 Hz range were found to be strongly correlated with tactile stimulation of lip and whisker (perioral) regions. These responses occurred regardless of whether the stimulus was externally or self-generated and during both active and passive touch. In contrast, perioral movements that did not tactually stimulate this region of the face (e.g., chewing) produced no detectable increases in GCL activity. In addition, GCL responses were not correlated with movement extremes. When rats used their lips actively for palpation and exploration, the tactile responses in the GCL were not detectably modulated by ongoing jaw movements. However, active palpation and exploratory behaviors did result in the largest and most continuous bursts of GCL activity: responses were on average 10% larger and 50% longer during palpation and exploration than during grooming or passive stimulation. Although activity levels differed between behaviors, the position and spatial extent of the peripheral receptive field was similar over all behaviors that resulted in tactile input. Overall, our data suggest that the 1000-4500 Hz multiunit responses in the Crus IIa GCL of awake rats are correlated with tactile input rather than with movement or any movement parameter and that these responses are likely to be of particular importance during the acquisition of sensory information by perioral structures.

  5. [Atrophy of the granular layer of the cerebellar cortex in patients with nonlymphoblastic leukemia treated with cytosine arabinoside].

    PubMed

    Nowacki, P; Dolińska, D; Honczarenko, K; Zyluk, B

    1992-01-01

    The reported analysis comprised 81 patients dying of acute non-lymphoblastic leukaemia type M1, M2, M4 and blastic crises in chronic myelocytic leukaemia. It was observed that the number of cases of cerebellar granular layer atrophy rose markedly in the years 1984-1990 as compared with 1976-1983 (45.4% vs 16.2%). It is suggested that this was due to the introduction of cytostatic treatment schedules with higher doses of cytosine arabinoside (ARAC), especially TAD (6-thioguanine, ARAC, daunorubicin). Cerebellar granular layer atrophy seems to be dependent rather on the cumulative dose of ARAC and not on a single high dose of that drug.

  6. Somatostatin binding to dissociated cells from rat cerebral cortex

    SciTech Connect

    Colas, B.; Prieto, J.C.; Arilla, E. )

    1990-11-01

    A method has been developed for the study of somatostatin (SS) binding to dissociated cells from rat cerebral cortex. Binding of {sup 125}I (Tyr11)SS to cells obtained by mechanical dissociation of rat cerebral cortex was dependent on time and temperature, saturable, reversible and highly specific. Under conditions of equilibrium, i.e., 60 min at 25 degrees C, native SS inhibited tracer binding in a dose-dependent manner. The Scatchard analysis of binding data was linear and yielded a dissociation constant of 0.60 +/- 0.08 nM with a maximal binding capacity of 160 +/- 16 fmol/mg protein. The binding of {sup 125}I (Tyr11)SS was specific as shown in experiments on tracer displacement by the native peptides, SS analogues, and unrelated peptides.

  7. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  8. Epidural motor cortex stimulation suppresses somatosensory evoked potentials in the primary somatosensory cortex of the rat.

    PubMed

    Chiou, Ruei-Jen; Lee, Hsiao-Yun; Chang, Chen-Wei; Lin, Kuan-Hung; Kuo, Chung-Chih

    2012-06-29

    Motor cortex stimulation (MCS) is a promising clinical procedure to help alleviate chronic pain. Animal models demonstrated that MCS is effective in lessening nocifensive behaviors. The present study explored the effects of MCS on cortical somatosensory evoked potentials (SEPs) recorded at the primary somatosensory cortex (SI) of the rat. SEPs were evoked by electrical stimulation applied to the contralateral forepaws. Effects of different intensities, frequencies, and durations of MCS were tested. MCS at ≥2V suppressed SEPs of the ipsilateral SI. Suppression lasted 120 min at an intensity of 5 V. The optimal frequency was 50 Hz, and the duration was 30s. In contrast, MCS did not affect SEPs recorded on the contralateral SI. Cortical stimulation out of the motor cortex did not induce a decrease in the ipsilateral SEPs. We also investigated involvement of the endogenous opioid system in this inhibition of SEPs induced by MCS. The opioid antagonist, naloxone (0.5 mg/kg), was administered 30 min before MCS. Application of naloxone completely prevented the inhibitory effect of MCS on ipsilateral SEPs. These results demonstrate that MCS blocked the transmission of somatosensory information to the primary somatosensory cortex, and this interference was mediated by the endogenous opioid system. This inhibitory effect on sensory transmission induced by MCS may reflect its antinociceptive effect.

  9. Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells.

    PubMed

    McKay, B E; Turner, R W

    2004-08-01

    The ability of cells to generate an appropriate spike output depends on a balance between membrane depolarizations and the repolarizing actions of K(+) currents. The high-voltage-activated Kv3 class of K(+) channels repolarizes Na(+) spikes to maintain high frequencies of discharge. However, little is known of the ability for these K(+) channels to shape Ca(2+) spike discharge or their ability to regulate Ca(2+) spike-dependent burst output. Here we identify the role of Kv3 K(+) channels in the regulation of Na(+) and Ca(2+) spike discharge, as well as burst output, using somatic and dendritic recordings in rat cerebellar Purkinje cells. Kv3 currents pharmacologically isolated in outside-out somatic membrane patches accounted for approximately 40% of the total K(+) current, were very fast and high voltage activating, and required more than 1 s to fully inactivate. Kv3 currents were differentiated from other tetraethylammonium-sensitive currents to establish their role in Purkinje cells under physiological conditions with current-clamp recordings. Dual somatic-dendritic recordings indicated that Kv3 channels repolarize Na(+) and Ca(2+) spikes, enabling high-frequency discharge for both types of cell output. We further show that during burst output Kv3 channels act together with large-conductance Ca(2+)-activated K(+) channels to ensure an effective coupling between Ca(2+) and Na(+) spike discharge by preventing Na(+) spike inactivation. By contributing significantly to the repolarization of Na(+) and especially Ca(2+) spikes, our data reveal a novel function for Kv3 K(+) channels in the maintenance of high-frequency burst output for cerebellar Purkinje cells.

  10. Functional specialization in rat occipital and temporal visual cortex

    PubMed Central

    Vermaercke, Ben; Gerich, Florian J.; Ytebrouck, Ellen; Arckens, Lutgarde; Van den Bergh, Gert

    2014-01-01

    Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. Anatomically, suggestions have been made about the existence of hierarchical pathways with similarities to the ventral and dorsal pathways in primates. Here we aimed to characterize some important functional properties in part of the supposed “ventral” pathway in rats. We investigated the functional properties along a progression of five visual areas in awake rats, from primary visual cortex (V1) over lateromedial (LM), latero-intermediate (LI), and laterolateral (LL) areas up to the newly found lateral occipito-temporal cortex (TO). Response latency increased >20 ms from areas V1/LM/LI to areas LL and TO. Orientation and direction selectivity for the used grating patterns increased gradually from V1 to TO. Overall responsiveness and selectivity to shape stimuli decreased from V1 to TO and was increasingly dependent upon shape motion. Neural similarity for shapes could be accounted for by a simple computational model in V1, but not in the other areas. Across areas, we find a gradual change in which stimulus pairs are most discriminable. Finally, tolerance to position changes increased toward TO. These findings provide unique information about possible commonalities and differences between rodents and primates in hierarchical cortical processing. PMID:24990566

  11. Neuronal activity in rat barrel cortex underlying texture discrimination.

    PubMed

    von Heimendahl, Moritz; Itskov, Pavel M; Arabzadeh, Ehsan; Diamond, Mathew E

    2007-11-01

    Rats and mice palpate objects with their whiskers to generate tactile sensations. This form of active sensing endows the animals with the capacity for fast and accurate texture discrimination. The present work is aimed at understanding the nature of the underlying cortical signals. We recorded neuronal activity from barrel cortex while rats used their whiskers to discriminate between rough and smooth textures. On whisker contact with either texture, firing rate increased by a factor of two to ten. Average firing rate was significantly higher for rough than for smooth textures, and we therefore propose firing rate as the fundamental coding mechanism. The rat, however, cannot take an average across trials, but must make an immediate decision using the signals generated on each trial. To estimate single-trial signals, we calculated the mutual information between stimulus and firing rate in the time window leading to the rat's observed choice. Activity during the last 75 ms before choice transmitted the most informative signal; in this window, neuronal clusters carried, on average, 0.03 bits of information about the stimulus on trials in which the rat's behavioral response was correct. To understand how cortical activity guides behavior, we examined responses in incorrect trials and found that, in contrast to correct trials, neuronal firing rate was higher for smooth than for rough textures. Analysis of high-speed films suggested that the inappropriate signal on incorrect trials was due, at least in part, to nonoptimal whisker contact. In conclusion, these data suggest that barrel cortex firing rate on each trial leads directly to the animal's judgment of texture.

  12. Calcium channels responsible for potassium-induced transmitter release at rat cerebellar synapses.

    PubMed Central

    Momiyama, A; Takahashi, T

    1994-01-01

    The effects of calcium channel blockers on potassium-induced transmitter release were studied in thin slices of cerebellum from neonatal rats using whole-cell patch clamp methods. Miniature inhibitory postsynaptic currents (mIPSCs) mediated by gamma-aminobutyric acid (GABA) were recorded from deep cerebellar nuclear neurones in the presence of tetrodotoxin. The frequency of mIPSCs was reproducibly increased by a brief application of high-potassium solution. In the presence of the L-type Ca2+ channel blocker nicardipine (10 microM), the potassium-induced increase in mIPSC frequency was suppressed by 49%. Neither the mean amplitude nor the time course of mIPSCs was affected by the blocker. The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTX, 3 microM) had no effect on the frequency of potassium-induced mIPSCs. The P-type Ca2+ channel blocker omega-Aga-IVA (200 nM) suppressed the potassium-induced increase in mIPSC frequency by 83% without affecting the mean amplitude or time course of mIPSCs. Comparing these data with previous studies of neurally evoked transmission, it is concluded that the Ca2+ channel subtypes responsible for potassium-induced transmitter release may be different from those mediating fast synaptic transmission. PMID:7913967

  13. Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na(+) currents through intracellular Ca(2+) release.

    PubMed

    Liu, Dong-Dong; Ren, Zhen; Yang, Guang; Zhao, Qian-Ru; Mei, Yan-Ai

    2014-06-01

    Although melatonin (MT) has been reported to protect cells against oxidative damage induced by electromagnetic radiation, few reports have addressed whether there are other protective mechanisms. Here, we investigated the effects of MT on extremely low-frequency electromagnetic field (ELF-EMF)-induced Nav activity in rat cerebellar granule cells (GCs). Exposing cerebellar GCs to ELF-EMF for 60 min. significantly increased the Nav current (INa ) densities by 62.5%. MT (5 μM) inhibited the ELF-EMF-induced INa increase. This inhibitory effect of MT is mimicked by an MT2 receptor agonist and was eliminated by an MT2 receptor antagonist. The Nav channel steady-state activation curve was significantly shifted towards hyperpolarization by ELF-EMF stimulation but remained unchanged by MT in cerebellar GC that were either exposed or not exposed to ELF-EMF. ELF-EMF exposure significantly increased the intracellular levels of phosphorylated PKA in cerebellar GCs, and both MT and IIK-7 did not reduce the ELF-EMF-induced increase in phosphorylated PKA. The inhibitory effects of MT on ELF-EMF-induced Nav activity was greatly reduced by the calmodulin inhibitor KN93. Calcium imaging showed that MT did not increase the basal intracellular Ca(2+) level, but it significantly elevated the intracellular Ca(2+) level evoked by the high K(+) stimulation in cerebellar GC that were either exposed or not exposed to ELF-EMF. In the presence of ruthenium red, a ryanodine-sensitive receptor blocker, the MT-induced increase in intracellular calcium levels was reduced. Our data show for the first time that MT protects against neuronal INa that result from ELF-EMF exposure through Ca(2+) influx-induced Ca(2+) release.

  14. Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na+ currents through intracellular Ca2+ release

    PubMed Central

    Liu, Dong-Dong; Ren, Zhen; Yang, Guang; Zhao, Qian-Ru; Mei, Yan-Ai

    2014-01-01

    Although melatonin (MT) has been reported to protect cells against oxidative damage induced by electromagnetic radiation, few reports have addressed whether there are other protective mechanisms. Here, we investigated the effects of MT on extremely low-frequency electromagnetic field (ELF-EMF)-induced Nav activity in rat cerebellar granule cells (GCs). Exposing cerebellar GCs to ELF-EMF for 60 min. significantly increased the Nav current (INa) densities by 62.5%. MT (5 μM) inhibited the ELF-EMF-induced INa increase. This inhibitory effect of MT is mimicked by an MT2 receptor agonist and was eliminated by an MT2 receptor antagonist. The Nav channel steady-state activation curve was significantly shifted towards hyperpolarization by ELF-EMF stimulation but remained unchanged by MT in cerebellar GC that were either exposed or not exposed to ELF-EMF. ELF-EMF exposure significantly increased the intracellular levels of phosphorylated PKA in cerebellar GCs, and both MT and IIK-7 did not reduce the ELF-EMF-induced increase in phosphorylated PKA. The inhibitory effects of MT on ELF-EMF-induced Nav activity was greatly reduced by the calmodulin inhibitor KN93. Calcium imaging showed that MT did not increase the basal intracellular Ca2+ level, but it significantly elevated the intracellular Ca2+ level evoked by the high K+ stimulation in cerebellar GC that were either exposed or not exposed to ELF-EMF. In the presence of ruthenium red, a ryanodine-sensitive receptor blocker, the MT-induced increase in intracellular calcium levels was reduced. Our data show for the first time that MT protects against neuronal INa that result from ELF-EMF exposure through Ca2+ influx-induced Ca2+ release. PMID:24548607

  15. Cytoarchitecture of mouse and rat cingulate cortex with human homologies.

    PubMed

    Vogt, Brent A; Paxinos, George

    2014-01-01

    A gulf exists between cingulate area designations in human neurocytology and those used in rodent brain atlases with a major underpinning of the former being midcingulate cortex (MCC). The present study used images extracted from the Franklin and Paxinos mouse atlas and Paxinos and Watson rat atlas to demonstrate areas comprising MCC and modifications of anterior cingulate (ACC) and retrosplenial cortices. The laminar architecture not available in the atlases is also provided for each cingulate area. Both mouse and rat have a MCC with neurons in all layers that are larger than in ACC and layer Va has particularly prominent neurons and reduced neuron densities. An undifferentiated ACC area 33 lies along the rostral callosal sulcus in rat but not in mouse and area 32 has dorsal and ventral subdivisions with the former having particularly large pyramidal neurons in layer Vb. Both mouse and rat have anterior and posterior divisions of retrosplenial areas 29c and 30, although their cytology is different in rat and mouse. Maps of the rodent cingulate cortices provide for direct comparisons with each region in the human including MCC and it is significant that rodents do not have a posterior cingulate region composed of areas 23 and 31 like the human. It is concluded that rodents and primates, including humans, possess a MCC and this homology along with those in ACC and retrosplenial cortices permit scientists inspired by human considerations to test hypotheses on rodent models of human diseases.

  16. Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide.

    PubMed Central

    McMillan, K; Bredt, D S; Hirsch, D J; Snyder, S H; Clark, J E; Masters, B S

    1992-01-01

    The endogenous formation of nitric oxide (NO) has become an area of intense interest as evidence for its biological functions has been obtained in three distinct tissues: circulating macrophages, in which it exerts cytotoxic effects; blood vessels, in which it has been identified as endothelium-derived relaxing factor; and neuronal cells, in which it functions as a neurotransmitter. The formation of NO in brain extracts has been shown to be catalyzed by an enzyme, termed NO synthase, which generates the NO responsible for stimulation of cGMP formation, the highest levels of which occur in the cerebellum. NO synthase catalyzes the formation of citrulline from arginine with the coincident production of NO and has been shown to be a flavoprotein, containing 1 mol each of FAD and FMN, tetrahydrobiopterin, and iron. It is also reported to contain an alpha-helical, calmodulin-binding consensus sequence consistent with its stimulation by calmodulin in the presence of Ca2+. The formation of NO requires incorporation of one of the atoms of molecular oxygen into one of the guanidinium nitrogen atoms of arginine with the coincident formation of citrulline. This communication reports that rat cerebellar NO synthase, cloned and stably expressed in human kidney 293 cells, contains heme in amounts stoichiometric with the flavins FAD and FMN as evidenced by the appearance of a pyridine hemochrome and a reduced CO difference spectrum with an absorbance maximum at approximately 445 nm. The finding of a CO-binding heme moiety explains the presence of iron in the enzyme and suggests a role for prosthetic heme as an oxygenase reaction center. This report also presents evidence for incorporation of delta-[14C]aminolevulinate specifically into immunoprecipitable NO synthase in stably transfected human kidney 293 cells but not in nontransfected cells. Simultaneously, K. A. White and M. A. Marletta [(1992) Biochemistry 31, 6627-6631] have demonstrated a CO-binding heme prosthetic group in

  17. Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.

    PubMed

    Negishi, Takayuki; Matsunaga, Yuki; Kobayashi, Yayoi; Hirano, Seishiro; Tashiro, Tomoko

    2013-12-01

    In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0-6 weeks of age] and/or late period [7-12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.

  18. Encoding of temporal intervals in the rat hindlimb sensorimotor cortex.

    PubMed

    Knudsen, Eric B; Flint, Robert D; Moxon, Karen A

    2012-01-01

    The gradual buildup of neural activity over experimentally imposed delay periods, termed climbing activity, is well documented and is a potential mechanism by which interval time is encoded by distributed cortico-thalamico-striatal networks in the brain. Additionally, when multiple delay periods are incorporated, this activity has been shown to scale its rate of climbing proportional to the delay period. However, it remains unclear whether these patterns of activity occur within areas of motor cortex dedicated to hindlimb movement. Moreover, the effects of behavioral training (e.g., motor tasks) under different reward conditions but with similar behavioral output are not well addressed. To address this, we recorded activity from the hindlimb sensorimotor cortex (HLSMC) of two groups of rats performing a skilled hindlimb press task. In one group, rats were trained only to a make a valid press within a finite window after cue presentation for reward (non-interval trained, nIT; n = 5), while rats in the second group were given duration-specific cues in which they had to make presses of either short or long duration to receive reward (interval trained, IT; n = 6). Using perievent time histogram (PETH) analyses, we show that cells recorded from both groups showed climbing activity during the task in similar proportions (35% IT and 47% nIT), however, only climbing activity from IT rats was temporally scaled to press duration. Furthermore, using single trial decoding techniques (Wiener filter), we show that press duration can be inferred using climbing activity from IT animals (R = 0.61) significantly better than nIT animals (R = 0.507, p < 0.01), suggesting IT animals encode press duration through temporally scaled climbing activity. Thus, if temporal intervals are behaviorally relevant then the activity of climbing neurons is temporally scaled to encode the passage of time.

  19. Encoding of temporal intervals in the rat hindlimb sensorimotor cortex

    PubMed Central

    Knudsen, Eric B.; Flint, Robert D.; Moxon, Karen A.

    2012-01-01

    The gradual buildup of neural activity over experimentally imposed delay periods, termed climbing activity, is well documented and is a potential mechanism by which interval time is encoded by distributed cortico-thalamico-striatal networks in the brain. Additionally, when multiple delay periods are incorporated, this activity has been shown to scale its rate of climbing proportional to the delay period. However, it remains unclear whether these patterns of activity occur within areas of motor cortex dedicated to hindlimb movement. Moreover, the effects of behavioral training (e.g., motor tasks) under different reward conditions but with similar behavioral output are not well addressed. To address this, we recorded activity from the hindlimb sensorimotor cortex (HLSMC) of two groups of rats performing a skilled hindlimb press task. In one group, rats were trained only to a make a valid press within a finite window after cue presentation for reward (non-interval trained, nIT; n = 5), while rats in the second group were given duration-specific cues in which they had to make presses of either short or long duration to receive reward (interval trained, IT; n = 6). Using perievent time histogram (PETH) analyses, we show that cells recorded from both groups showed climbing activity during the task in similar proportions (35% IT and 47% nIT), however, only climbing activity from IT rats was temporally scaled to press duration. Furthermore, using single trial decoding techniques (Wiener filter), we show that press duration can be inferred using climbing activity from IT animals (R = 0.61) significantly better than nIT animals (R = 0.507, p < 0.01), suggesting IT animals encode press duration through temporally scaled climbing activity. Thus, if temporal intervals are behaviorally relevant then the activity of climbing neurons is temporally scaled to encode the passage of time. PMID:23055956

  20. The representation of social facial touch in rat barrel cortex.

    PubMed

    Bobrov, Evgeny; Wolfe, Jason; Rao, Rajnish P; Brecht, Michael

    2014-01-06

    Controlled presentation of stimuli to anesthetized [1] or awake [2] animals suggested that neurons in sensory cortices respond to elementary features [3, 4], but we know little about neuronal responses evoked by social interactions. Here we investigate processing in the barrel cortex of rats engaging in social facial touch [5, 6]. Sensory stimulation by conspecifics differs from classic whisker stimuli such as deflections, contact poles [7, 8], or textures [9, 10]. A large fraction of barrel cortex neurons responded to facial touch. Social touch responses peaked when animals aligned their faces and contacted each other by multiple whiskers with small, irregular whisker movements. Object touch was associated with larger, more regular whisker movements, and object responses were weaker than social responses. Whisker trimming abolished responses. During social touch, neurons in males increased their firing on average by 44%, while neurons in females increased their firing by only 19%. In females, socially evoked and ongoing firing rates were more than 1.5-fold higher in nonestrus than in estrus. Barrel cortex represented socially different contacts by distinct firing rates, and the variation of activity with sex and sexual status could contribute to the generation of gender-specific neural constructs of conspecifics.

  1. Ontogeny of somatostatin receptors in the rat somatosensory cortex

    SciTech Connect

    Gonzalez, B.J.; Leroux, P.; Bodenant, C.; Vaudry, H. )

    1991-03-08

    The distribution and density of SRIF receptors (SRIF-R) were studied during development in the rat somatosensory cortex by in vitro autoradiography with monoiodinated (Tyr0-DTrp8)S14. In 16-day-old fetuses (E16), intense labeling was evident in the intermediate zone of the cortex while low concentrations of SRIF-R were detected in the marginal and ventricular zones. The highest density of SRIF-R was measured in the intermediate zone at E18. At this stage, labeling was also intense in the internal part of the developing cortical plate; in contrast, the concentration of binding sites associated with the marginal and ventricular zones remained relatively low. Profound modifications in the distribution of SRIF-R appeared at birth. In particular, a transient reduction of receptor density occurred in the cortical plate. During the first postnatal week, the density of receptors measured in the intermediate zone decreased gradually; conversely, high levels of SRIF-R were observed in the developing cortical layers (II to VI). At postpartum day 13 (P13), a stage which just precedes completion of cell migration in the parietal cortex, the most intensely labeled regions were layers V-VI and future layers II-III. From P13 to adulthood, the concentrations of SRIF-R decreased in all cortical layers (I to VI) and the pattern of distribution of receptors at P21 was similar to that observed in the adults.

  2. Acute and chronic administration of ibogaine to the rat results in astrogliosis that is not confined to the cerebellar vermis.

    PubMed

    O'Callaghan, J P; Rogers, T S; Rodman, L E; Page, J G

    1996-10-31

    Acute administration of high doses of ibogaine (IBG) to the male rat results in degeneration of Purkinje cells and reactive gliosis in the cerebellar vermis. We examined whether acute and chronic administration of IBG to male and female rats results in gliosis as determined by quantification of the astroglial intermediate filament protein, glial fibrillary acidic protein (GFAP). After acute administration of IBG, rats of both sexes showed dose-related increases in GFAP that were not confined to the cerebellar vermis. After chronic administration of IBG, female, but not male rats, showed large (as much as 200% of control), dose-related increases in GFAP in hippocampus, olfactory bulbs, brain stem and striatum, but not cerebellum. In hippocampus, the cytoskeletal proteins, neurofilament 68 (NF-68) and beta-tubulin were increased in females treated chronically with IBG, findings consistent with a damage-induced sprouting response. Together, the data indicate that IBG damages areas of the brain outside the cerebellum and that the sites damaged are dependent on sex and dosage regimen.

  3. Neural discriminability in rat lateral extrastriate cortex and deep but not superficial primary visual cortex correlates with shape discriminability.

    PubMed

    Vermaercke, Ben; Van den Bergh, Gert; Gerich, Florian; Op de Beeck, Hans

    2015-01-01

    Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. It is unknown to what degree this functional organization is related to the well-known hierarchical organization of the visual system in primates. We designed a study in rats that targets one of the hallmarks of the hierarchical object vision pathway in primates: selectivity for behaviorally relevant dimensions. We compared behavioral performance in a visual water maze with neural discriminability in five visual cortical areas. We tested behavioral discrimination in two independent batches of six rats using six pairs of shapes used previously to probe shape selectivity in monkey cortex (Lehky and Sereno, 2007). The relative difficulty (error rate) of shape pairs was strongly correlated between the two batches, indicating that some shape pairs were more difficult to discriminate than others. Then, we recorded in naive rats from five visual areas from primary visual cortex (V1) over areas LM, LI, LL, up to lateral occipito-temporal cortex (TO). Shape selectivity in the upper layers of V1, where the information enters cortex, correlated mostly with physical stimulus dissimilarity and not with behavioral performance. In contrast, neural discriminability in lower layers of all areas was strongly correlated with behavioral performance. These findings, in combination with the results from Vermaercke et al. (2014b), suggest that the functional specialization in rodent lateral visual cortex reflects a processing hierarchy resulting in the emergence of complex selectivity that is related to behaviorally relevant stimulus differences.

  4. 2', 3'-cyclic nucleotide 3'-phosphodiesterase is expressed in dissociated rat cerebellar cells and included in the postsynaptic density fraction.

    PubMed

    Cho, Sun-Jung; Jung, Jae Seob; Jin, IngNyol; Moon, Il Soo

    2003-08-31

    We have shown by protein sequencing that the phosphotyrosine-containing 48 kDa protein band of the rat cerebellar postsynaptic density fraction (CBL-PSD) is 2', 3'-cyclic nucleotide 3'-phosphodiesterase 2 (CNP2). Immunoblot analysis indicated that both CNP1 and CNP2 isoforms are present in the CBL-PSD fraction, whereas there is little CNP2 in the forebrain (FB)-PSD fraction. Both isoforms in the CBL-PSD fraction were tyrosine-phosphorylated to a basal extent. They were efficiently dissociated from the complexes in the PSD fraction by salt, but not by non-ionic detergents such as n-octyl glucoside (OG) and Triton X-100. Immunocytochemistry of dissociated cerebellar cultures revealed patchy CNP staining in oligodendrocytes (OLs), Purkinje cells (PCs), and unidentified PSD95-positive cells, but no staining in granule cells (GCs). Our results indicate that both CNP1 and CNP2 are expressed in cerian populations of cerebellar cells in addition to OL, and that they are associated with complexes that are co-isolated with the PSD.

  5. Ischemia deteriorates the spike encoding of rat cerebellar Purkinje cells by raising intracellular Ca{sup 2+}

    SciTech Connect

    Zhao Shidi; Chen Na; Yang Zhilai; Huang Li; Zhu Yan; Guan Sudong; Chen Qianfen; Wang Jinhui

    2008-02-08

    Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to a persistent glutamate action. To the fact that they are more vulnerable to ischemia than other glutamate-innervated neurons, we studied whether additional mechanisms are present and whether cytoplasm Ca{sup 2+} plays a key role in their ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells were measured by whole-cell recording in cerebellar slices of rats with less glutamate action. The role of cytoplasm Ca{sup 2+} was examined by two-photon cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje cells. These changes were associated with the reduction of spike refractory periods and threshold potentials, as well as the loss of their control to spike encoding. Ischemia-induced functional deterioration at Purkinje neurons was accompanied by cytoplasm Ca{sup 2+} rise and prevented by BAPTA infusion. Therefore, the ischemia destabilizes the spike encoding of Purkinje cells via raising cytoplasm Ca{sup 2+} without a need for glutamate, which subsequently causes their excitotoxic death.

  6. Multiple pathways of Pb(2+) permeation in rat cerebellar granule neurones.

    PubMed

    Mazzolini, M; Traverso, S; Marchetti, C

    2001-10-01

    The pathways of lead (Pb(2+)) uptake were studied in fura-2-loaded cerebellar granule cells from 8-day-old rats. In a nominal Ca-free external bath, Pb(2+) (5-50 microM) determined an increase of the fluorescence emission ratio (R = E(340)/E(380)) even in the absence of any specific stimulus. This rise was dose-dependent, was not significantly affected by mM Mg(2+) or Ca(2+), but it was readily reversed by the membrane-permeant heavy metal chelator tetrakis(2-pyridylmethyl) ethylene-diamine (TPEN, 100 microM), indicating that it was due to Pb(2+) influx. The rate of rise, dR/dt, was increased up to a factor of 5 by depolarizing high-KCl solution, indicating a sizeable permeation through voltage-dependent channels. This effect was neither antagonized by nimodipine, nor enhanced by BayK8644, but it was slackened by omega-agatoxin IVA (200 nM), suggesting an involvement of non-L-type calcium channels. Pb(2+) influx was also stimulated by glutamic acid or NMDA in the presence of 10-30 microM glycine, but only in Mg-free solution, suggesting that glutamate channels of the NMDA type are an additional pathway of Pb(2+) uptake. Pb(2+) caused a time-, dose- and stimulus-dependent saturation of the dye, whose intracellular concentration is approximately 10 microM, indicating that intracellular Pb(2+) can readily reach a concentration in the micromolar range. These results indicate that the particular vulnerability of neurones to Pb(2+) poisoning is linked to the presence of specific transport systems, which mediate the rapid uptake of Pb(2+) into the neurone.

  7. Intra-cerebellar infusion of the protein kinase Mzeta (PKMζ) inhibitor ZIP disrupts eyeblink classical conditioning

    PubMed Central

    Chihabi, Kutibh; Morielli, Anthony D.; Green, John T.

    2016-01-01

    PKM-ζ, a constitutively active N-terminal truncated form of PKC-ζ, has long been implicated in a cellular correlate of learning, long-term potentiation (LTP). Inhibition of PKM-ζ with Zeta-inhibitory peptide (ZIP) has been shown in many brain structures to disrupt maintenance of AMPA receptors, irreversibly disrupting numerous forms of learning and memory that have been maintained for weeks. Delay eyeblink conditioning (EBC) is an established model for the assessment of cerebellar learning; here, we show that PKC-ζ and PKM-ζ are highly expressed in the cerebellar cortex, with highest expression found in Purkinje cell (PC) nuclei. Despite being highly expressed in the cerebellar cortex, no studies have examined how regulation of cerebellar PKM-ζ may affect cerebellar-dependent learning and memory. Given its disruption of learning in other brain structures, we hypothesized that ZIP would also disrupt delay EBC. We have shown that infusion of ZIP into the lobulus simplex of the rat cerebellar cortex can indeed significantly disrupt delay EBC. PMID:26949968

  8. Effects of differential interference with postnatal cerebellar neurogenesis on motor performance, activity level, and maze learning of rats: a developmental study.

    PubMed

    Pellegrino, L J; Altman, J

    1979-02-01

    The region of the cerebellum was X-irradiated in infant rats with selected exposure schedules designed to produce animals in which the cerebellar cortex was (a) essentially normal except for agenesis of late forming granule cells with axons situated in the uppermost molecular layer (12--15X), (b) lacking in stellate cells, with a severe reduction in granule cells with axons in the upper molecular layer (8--15X), (c) morphologically disorganized but had only intermediate cell agenesis (4--5X), or (d) disorganized and devoid of practically all postnatally forming interneurons (4--15X). In the first two experiments young adults had to traverse rotating rods that differed in texture and types of obstacles. The 8--15X animals showed no deficits on any of the rods tested. The third study dealt with spontaneous motor performance in the open field at three ages. The 4--5X and 4--15X animals were hypoactive as infants and young adults; this was attributed to their motor deficits. The 8--15X and 12--15X animals were hyperactive in the open field as young adults. The fourth experiment examined intra- and/or intersession habituation. No group differences were found in habituation patterns. In the fifth experiment, using activity wheels, the 4--15X group was hypoactive, and the 8--15X and 12--15X groups were hyperactive as young adults. In the sixth experiment young adults were tested for learning performance in a multiple-unit water maze. The 4--15X group was deficient on single alternation; the 4--5X and 12--15X groups on double alternation. The seventh experiment shed some light on the single alternation deficit of the 4--15X group; only these animals failed to alternate spontaneously in a nonaversive situation. In conclusion, these behavioral results, combined with those of recent morphological investigations, suggest that the cerebellar cortex is hierarchically organized: The basal domain of Purkinje cells and the lower molecular layer are implicated in the coordination of

  9. Effect of locomotor activity on ultrastructure of cerebellar neurons, neurological disturbances, and survival of Krushinsky-Molodkina rats with hemorrhagic stroke.

    PubMed

    Samosudova, N V; Reutov, V P; Krushinsky, A L; Kuzenkov, V S; Sorokina, E G

    2012-10-01

    We studied the effect of locomotor activity on the ultrastructure of cerebellar neurons, neurological disturbances, and survival rate in Krushinsky-Molodkina rats during the development of hemorrhagic induced by acoustic stress. In animals with high spontaneous locomotor activity, severe edema of cerebellar neurons (resulting in the destruction of surrounding structures) and swelling of the synapses (terminals of mossy fibers on granule cell dendrites) were observed. By contrast, the areas of intracerebral, subdural, and subarachnoid hemorrhages were lower in rats under conditions of forced rest.

  10. Sexually Monomorphic Maps and Dimorphic Responses in Rat Genital Cortex.

    PubMed

    Lenschow, Constanze; Copley, Sean; Gardiner, Jayne M; Talbot, Zoe N; Vitenzon, Ariel; Brecht, Michael

    2016-01-11

    Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain.

  11. Auditory, Somatosensory, and Multisensory Insular Cortex in the Rat

    PubMed Central

    Rodgers, Krista M.; Benison, Alexander M.; Klein, Andrea

    2008-01-01

    Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning. PMID:18424777

  12. Hyperspectral optical tomography of intrinsic signals in the rat cortex

    PubMed Central

    Konecky, Soren D.; Wilson, Robert H.; Hagen, Nathan; Mazhar, Amaan; Tkaczyk, Tomasz S.; Frostig, Ron D.; Tromberg, Bruce J.

    2015-01-01

    Abstract. We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5 Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652 nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin (ctHbO2) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in ctHbO2 and ctHb were found to occur at 0.29±0.02 and 0.66±0.04  mm beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in ctHbO2 and ctHb of 321±53 and 555±96  nM, respectively, with these maximum changes occurring at 4±0.2  s poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer–Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects. PMID:26835483

  13. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  14. Down regulation of cerebellar serotonergic receptors in streptozotocin induced diabetic rats: Effect of pyridoxine and Aegle marmelose.

    PubMed

    Abraham, Pretty Mary; Paul, Jes; Paulose, C S

    2010-04-29

    Oxidative stress plays an important role in cerebellar damage caused by diabetes, leading to deterioration in glucose homeostasis causing metabolic disorders. The present study was carried out to find the effects of Aegle marmelose leaf extract and insulin alone and in combination with pyridoxine on the cerebellar 5-HT through 5-HT(2A) receptor subtype, gene expression studies on the status of antioxidants-superoxide dismutase (SOD), glutathione peroxidase (GPx), 5-HT(2A) and 5-HT transporter (5-HTT) and immunohistochemical studies in streptozotocin induced diabetic rats. 5-HT and 5-HT(2A) receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in the cerebellum of diabetic rats compared to control. Gene expression studies of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum showed a significant down regulation (p<0.001) in diabetic rats compared to control. Pyridoxine treated alone and in combination with insulin, A. marmelose to diabetic rats reversed the B(max), K(d) of 5-HT, 5-HT(2A) and the gene expression of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Also, the Rotarod test confirms the motor dysfunction and recovery by treatment. These data suggest the antioxidant and neuroprotective role of pyridoxine and A. marmelose through the up regulation of 5-HT through 5-HT(2A) receptor in diabetic rats. Our results suggest that pyridoxine treated alone and in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalizing diabetic related oxidative stress and neurodegeneration affecting the motor ability of an individual by serotonergic receptors through 5-HT(2A) function. This has clinical significance in the management of diabetes.

  15. Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex.

    PubMed

    Canto, Cathrin B; Witter, Menno P

    2012-06-01

    Principal neurons in different medial entorhinal cortex (MEC) layers show variations in spatial modulation that stabilize between 15 and 30 days postnatally. These in vivo variations are likely due to differences in intrinsic membrane properties and integrative capacities of neurons. The latter depends on inputs and thus potentially on the morphology of principal neurons. In this comprehensive study, we systematically compared the morphological and physiological characteristics of principal neurons in all MEC layers of newborn rats before and after weaning. We recorded simultaneously from up to four post-hoc morphologically identified MEC principal neurons in vitro. Neurons in L(ayer) I-LIII have dendritic and axonal arbors mainly in superficial layers, and LVI neurons mainly in deep layers. The dendritic and axonal trees of part of LV neurons diverge throughout all layers. Physiological properties of principal neurons differ between layers. In LII, most neurons have a prominent sag potential, resonance and membrane oscillations. Neurons in LIII and LVI fire relatively regular, and lack sag potentials and membrane oscillations. LV neurons show the most prominent spike-frequency adaptation and highest input resistance. The data indicate that adult-like principal neuron types can be differentiated early on during postnatal development. The results of the accompanying paper, in which principal neurons in the lateral entorhinal cortex (LEC) were described (Canto and Witter,2011), revealed that significant differences between LEC and MEC exist mainly in LII neurons. We therefore systematically analyzed changes in LII biophysical properties along the mediolateral axis of MEC and LEC. There is a gradient in properties typical for MEC LII neurons. These properties are most pronounced in medially located neurons and become less apparent in more laterally positioned ones. This gradient continues into LEC, such that in LEC medially positioned neurons share some properties

  16. Bilateral receptive fields of cells in rat Sm1 cortex.

    PubMed

    Armstrong-James, M; George, M J

    1988-01-01

    Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N = 44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1 +/- 9.1 ms (S.D) cf. 26.4 +/- 7.2 ms, N = 44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20-200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0-900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed

  17. Perirhinal Cortex Lesions in Rats: Novelty Detection and Sensitivity to Interference

    PubMed Central

    2015-01-01

    Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1–4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal. PMID:26030425

  18. Infralimbic Prefrontal Cortex is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats

    PubMed Central

    Peters, Jamie; LaLumiere, Ryan T.; Kalivas, Peter W.

    2008-01-01

    The rat prelimbic prefrontal cortex and nucleus accumbens core are critical for initiating cocaine seeking. In contrast, the neural circuitry responsible for inhibiting cocaine seeking during extinction is unknown. The present findings using inhibition of selected brain nuclei with GABA agonists show that the suppression of cocaine seeking produced by prior extinction training required activity in the rat infralimbic cortex. Conversely, the reinstatement of drug seeking by a cocaine injection in extinguished animals was suppressed by increasing neuronal activity in infralimbic cortex with the glutamate agonist AMPA. The cocaine seeking induced by inactivating infralimbic cortex resembled other forms of reinstated drug seeking by depending on activity in prelimbic cortex and the basolateral amygdala. A primary efferent projection from the infralimbic cortex is to the nucleus accumbens shell. Akin to infralimbic cortex, inhibition of the accumbens shell induced cocaine seeking in extinguished rats. However, bilateral inhibition of the shell also elicited increased locomotor activity. Nonetheless, unilateral inhibition of the accumbens shell did not increase motor activity, and simultaneous unilateral inactivation of the infralimbic cortex and shell induced cocaine seeking, suggesting that an interaction between these two structures is necessary for extinction training to inhibit cocaine seeking. The infralimbic cortex and accumbens shell appear to be recruited by extinction learning because inactivation of these structures prior to extinction training did not alter cocaine seeking. Together, these findings suggest that a neuronal network involving the infralimbic cortex and accumbens shell is recruited by extinction training to suppress cocaine seeking. PMID:18524910

  19. Cerebellar Development and Disease

    PubMed Central

    Gleeson, Joseph G.

    2008-01-01

    Recent Advances The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitter-specific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum. PMID:18513948

  20. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    SciTech Connect

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  1. Ablation of Cerebellar Nuclei Prevents H-Reflex Down-Conditioning in Rats

    ERIC Educational Resources Information Center

    Chen, Xiang Yang; Wolpaw, Jonathan R.

    2005-01-01

    While studies of cerebellar involvement in learning and memory have described plasticity within the cerebellum, its role in acquisition of plasticity elsewhere in the CNS is largely unexplored. This study set out to determine whether the cerebellum is needed for acquisition of the spinal cord plasticity that underlies operantly conditioned…

  2. Adaptation to sensory stimulation in the Rat Barrel Cortex

    NASA Astrophysics Data System (ADS)

    Heiss, Jaime

    Sustained stimulation of sensory organs results in adaptation of the neuronal response along the sensory pathway. Whether or not cortical adaptation affects equally excitatory and inhibitory inputs is poorly understood. This question was examined using patch recordings of neurons in the barrel cortex of anesthetized rats while repetitively stimulating the principal whisker. After characterizing the excitation and inhibition evoked either by single or double whisker deflection or by different stimulation strengths, it was found that inhibition, unlike excitation, sums linearly and adapts more, causing the balance between these inputs to shift towards excitation. A comparison of the latency of thalamic firing and evoked synaptic inputs in the cortex strongly suggests that adaptation of inhibition results mostly from depression of inhibitory synapses rather than reduction in the firing of inhibitory cells. A similar change in the balance was reproduced by a simple feedforward model. The differential adaptation of the synaptic inputs that shifts the balance toward excitation may act as a gain mechanism which enhances the subthreshold response during sustained stimulation, despite a reduction in excitation. Natural sensory stimulation rarely arrives in an isolated manner, but in a context of several stimulations, like when a rat sweeps its whisker along a surface with a given texture. It was shown that individual single cells sporadically fail to respond, in a very variable fashion from trial to trial. Whether or not adaptation is correlated among neighboring neurons or is it a private, independent phenomenon was investigated by performing simultaneous recordings. Neighboring neurons presented a highly correlated responsiveness to repetitive stimulation, which strongly varied from trial to trial in a synchronized way. Population averages of a single trial obtained by LFP recordings and VSD imaging differed considerably from the time average but was highly correlated to

  3. Dysgranular Retrosplenial Cortex Lesions in Rats Disrupt Cross-Modal Object Recognition

    ERIC Educational Resources Information Center

    Hindley, Emma L.; Nelson, Andrew J. D.; Aggleton, John P.; Vann, Seralynne D.

    2014-01-01

    The retrosplenial cortex supports navigation, with one role thought to be the integration of different spatial cue types. This hypothesis was extended by examining the integration of nonspatial cues. Rats with lesions in either the dysgranular subregion of retrosplenial cortex (area 30) or lesions in both the granular and dysgranular subregions…

  4. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    ERIC Educational Resources Information Center

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  5. A Novel Role for the Rat Retrosplenial Cortex in Cognitive Control

    ERIC Educational Resources Information Center

    Nelson, Andrew J. D.; Hindley, Emma L.; Haddon, Josephine E.; Vann, Seralynne D.; Aggleton, John P.

    2014-01-01

    By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first…

  6. Patterned expression of a cocaine- and amphetamine-regulated transcript peptide reveals complex circuit topography in the rodent cerebellar cortex.

    PubMed

    Reeber, Stacey L; Sillitoe, Roy V

    2011-06-15

    The cerebellum (Cb) of mammals and birds consists of an evolutionarily conserved map defined by Purkinje cell (PC) protein expression. In mice, ZebrinII/aldolaseC is expressed in a striking array of stripes in lobules I-V (anterior zone; AZ) and VIII-anterior IX (posterior zone; PZ), whereas the small heat shock protein 25 (HSP25) is expressed in stripes in lobules VI-VII (central zone, CZ) and posterior IX-X (nodular zone, NZ). Little is known about whether molecularly defined afferent subsets terminate within specific PC stripes or whether their topography is conserved across species. Using immunohistochemistry, we demonstrate in adult mice and rats that cocaine- and amphetamine-regulated transcript (CART) expression can be used to partition sensory-motor projections into complex topographic maps. We found that in mice CART was expressed in climbing fiber bands that generally corresponded to the pattern of HSP25-expressing PCs in the CZ/NZ. In contrast, CART was expressed in climbing fiber bands in all four transverse zones of the rat Cb. Within the rat AZ/PZ, climbing fibers terminated selectively within the dendrites of ZebrinII-immunoreactive PCs. In additional experiments, we observed CART expression in loose clusters of spinocerebellar mossy fibers in the mouse AZ/PZ, whereas in rat CART immunoreactive mossy fibers terminated predominantly in the CZ/NZ. We conclude that, although the overall topography of CART-expressing afferents is restricted within a conserved map of PC stripes and transverse zones, their termination patterns also reflect species-specific compartmental features.

  7. Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices

    PubMed Central

    Cooper, Elizabeth J; Johnston, Graham A R; Edwards, Frances A

    1999-01-01

    The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages (≈10 and ≈20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a ≈4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 μm). Similar effects were seen at high concentrations of THDOC (1-2 μm) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. The effects of THDOC (1 μm) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. At concentrations of THDOC likely to occur physiologically (50–100 nm), the decay time of IPSCs was also enhanced (25–50 %) in all cerebellar cell groups tested. In contrast, at 100 nm THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the δ subunit of the GABAA receptor and possibly an increase in the α4 subunit. PMID:10581314

  8. Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex

    PubMed Central

    Tsutsui-Kimura, Iku; Yoshida, Takayuki; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2015-01-01

    Background: Deficits in impulse control are often observed in psychiatric disorders in which abnormalities of the prefrontal cortex are observed, including attention-deficit/hyperactivity disorder and bipolar disorder. We recently found that milnacipran, a serotonin/noradrenaline reuptake inhibitor, could suppress impulsive action in normal rats. However, whether milnacipran could suppress elevated impulsive action in rats with lesions of the ventromedial prefrontal cortex, which is functionally comparable with the human prefrontal cortex, remains unknown. Methods: Selective lesions of the ventromedial prefrontal cortex were made using quinolinic acid in rats previously trained on a 3-choice serial reaction time task. Sham rats received phosphate buffered saline. Following a period of recovery, milnacipran (0 or 10mg/kg/d × 14 days) was orally administered 60 minutes prior to testing on the 3-choice task. After 7 days of drug cessation, Western blotting, immunohistochemistry, electrophysiological analysis, and morphological analysis were conducted. Results: Lesions of the ventromedial prefrontal cortex induced impulsive deficits, and repeated milnacipran ameliorated the impulsive deficit both during the dosing period and after the cessation of the drug. Repeated milnacipran remediated the protein levels of mature brain-derived neurotrophic factor and postsynaptic density-95, dendritic spine density, and excitatory currents in the few surviving neurons in the ventromedial prefrontal cortex of ventromedial prefrontal cortex-lesioned rats. Conclusions: The findings of this study suggest that milnacipran treatment could be a novel strategy for the treatment of psychiatric disorders that are associated with a lack of impulse control. PMID:25522418

  9. Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Aguirre, A. D.; Chen, Y.; Fujimoto, J. G.; Ruvinskaya, L.; Devor, A.; Boas, D. A.

    2006-12-01

    Co-registered optical coherence tomography (OCT) and video microscopy of the rat somatosensory cortex were acquired simultaneously through a thinned skull during forepaw electrical stimulation. Fractional signal change measured by OCT revealed a functional signal time course corresponding to the hemodynamic signal measurement made with video microscopy. OCT can provide high-resolution, cross-sectional images of functional neurovascular activation and may offer a new tool for basic neuroscience research in the important rat cerebral cortex model.

  10. Specific receptor binding of atrial natriuretic peptide to rat renal cortex

    SciTech Connect

    Ogura, T.; Mitsui, T.; Ogawa, N.; Ota, Z.

    1985-09-01

    Radiolabeled receptor assay (RRA) of atrial natriuretic peptide (ANP) was studied in rat kidney membranes. Binding of ( SVI)-ANP to membrane preparations of rat whole kidney was saturated and show a high affinity. Furthermore, renal cortex membrane had a higher affinity for ANP binding site than renal medulla membrane. This high affinity ANP receptor site in renal cortex membrane indicated that ANP controlled the balance of water and sodium excretion due to this receptor site in the kidney.

  11. Exercise-induced changes of the capillaries in the cortex of middle-aged rats.

    PubMed

    Huang, C-X; Qiu, X; Wang, S; Wu, H; Xia, L; Li, C; Gao, Y; Zhang, L; Xiu, Y; Chao, F; Tang, Y

    2013-03-13

    Previous studies have shown that running exercise could increase regional cerebral blood flow. There have been previous studies investigating the effects of running exercise on capillary density in the brain and showing that running exercise could induce brain angiogenesis. However, there have been no studies investigating the effects of running exercise on the total volume, total length and total surface area of the capillaries in the cortex. Moreover, sex differences in the effects of running exercise on the capillaries of the cortex have not previously been investigated. The current study was designed to investigate the effects of running exercise on the capillaries in the cortex of middle-aged rats using the new unbiased stereological methods. The present study found that the total length and total surface area of the capillaries in the cortex of running middle-aged female rats were significantly increased, compared to control rats. Our results also reveal that there are sex differences in the effects of running exercise on the capillaries in the cortex of middle-aged rats. These results demonstrate that exercise-induced increases of the capillaries in the female rat cortex might be one of the structural bases for the exercise-induced improvement in the spatial learning capacity of middle-aged female rats. These results provide a baseline for further studies that search for strategies to delay the deleterious effects of brain aging.

  12. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons

    PubMed Central

    Tan, Y P; Llano, I

    1999-01-01

    Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. α-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; α-dendrotoxin had no effect. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, α-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. α-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening. PMID:10517801

  13. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    PubMed

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  14. High dosage of monosodium glutamate causes deficits of the motor coordination and the number of cerebellar Purkinje cells of rats.

    PubMed

    Prastiwi, D; Djunaidi, A; Partadiredja, G

    2015-11-01

    Monosodium glutamate (MSG) has been widely used throughout the world as a flavoring agent of food. However, MSG at certain dosages is also thought to cause damage to many organs, including cerebellum. This study aimed at investigating the effects of different doses of MSG on the motor coordination and the number of Purkinje cells of the cerebellum of Wistar rats. A total of 24 male rats aged 4 to 5 weeks were divided into four groups, namely, control (C), T2.5, T3, and T3.5 groups, which received intraperitoneal injection of 0.9% sodium chloride solution, 2.5 mg/g body weight (bw) of MSG, 3.0 mg/g bw of MSG, and 3.5 mg/g bw of MSG, respectively, for 10 consecutive days. The motor coordination of the rats was examined prior and subsequent to the treatment. The number of cerebellar Purkinje cells was estimated using physical fractionator method. It has been found that the administration of MSG at a dosage of 3.5 mg/g bw, but not at lower dosages, caused a significant decrease of motor coordination and the estimated total number of Purkinje cells of rats. There was also a significant correlation between motor coordination and the total number of Purkinje cells.

  15. Ginsenoside Rg1 prevents cerebral and cerebellar injury induced by obstructive jaundice in rats via inducing expression of TIPE-2.

    PubMed

    Zhou, Tingting; Zu, Guo; Zhou, Lu; Che, Ningwei; Guo, Jing; Liang, Zhanhua

    2016-01-01

    The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats.

  16. Masking reduces orientation selectivity in rat visual cortex.

    PubMed

    Alwis, Dasuni S; Richards, Katrina L; Price, Nicholas S C

    2016-11-01

    In visual masking the perception of a target stimulus is impaired by a preceding (forward) or succeeding (backward) mask stimulus. The illusion is of interest because it allows uncoupling of the physical stimulus, its neuronal representation, and its perception. To understand the neuronal correlates of masking, we examined how masks affected the neuronal responses to oriented target stimuli in the primary visual cortex (V1) of anesthetized rats (n = 37). Target stimuli were circular gratings with 12 orientations; mask stimuli were plaids created as a binarized sum of all possible target orientations. Spatially, masks were presented either overlapping or surrounding the target. Temporally, targets and masks were presented for 33 ms, but the stimulus onset asynchrony (SOA) of their relative appearance was varied. For the first time, we examine how spatially overlapping and center-surround masking affect orientation discriminability (rather than visibility) in V1. Regardless of the spatial or temporal arrangement of stimuli, the greatest reductions in firing rate and orientation selectivity occurred for the shortest SOAs. Interestingly, analyses conducted separately for transient and sustained target response components showed that changes in orientation selectivity do not always coincide with changes in firing rate. Given the near-instantaneous reductions observed in orientation selectivity even when target and mask do not spatially overlap, we suggest that monotonic visual masking is explained by a combination of neural integration and lateral inhibition.

  17. A model of long-term memory storage in the cerebellar cortex: a possible role for plasticity at parallel fiber synapses onto stellate/basket interneurons.

    PubMed

    Kenyon, G T

    1997-12-09

    By evoking changes in climbing fiber activity, movement errors are thought to modify synapses from parallel fibers onto Purkinje cells (pf*Pkj) so as to improve subsequent motor performance. Theoretical arguments suggest there is an intrinsic tradeoff, however, between motor adaptation and long-term storage. Assuming a baseline rate of motor errors is always present, then repeated performance of any learned movement will generate a series of climbing fiber-mediated corrections. By reshuffling the synaptic weights responsible for any given movement, such corrections will degrade the memories for other learned movements stored in overlapping sets of synapses. The present paper shows that long-term storage can be accomplished by a second site of plasticity at synapses from parallel fibers onto stellate/basket interneurons (pf*St/Bk). Plasticity at pf*St/Bk synapses can be insulated from ongoing fluctuations in climbing fiber activity by assuming that changes in pf*St/Bk synapses occur only after changes in pf*Pkj synapses have built up to a threshold level. Although climbing fiber-dependent plasticity at pf*Pkj synapses allows for the exploration of novel motor strategies in response to changing environmental conditions, plasticity at pf*St/Bk synapses transfers successful strategies to stable long-term storage. To quantify this hypothesis, both sites of plasticity are incorporated into a dynamical model of the cerebellar cortex and its interactions with the inferior olive. When used to simulate idealized motor conditioning trials, the model predicts that plasticity develops first at pf*Pkj synapses, but with additional training is transferred to pf*St/Bk synapses for long-term storage.

  18. The perirhinal cortex and long-term spatial memory in rats.

    PubMed

    Ramos, Juan M J

    2002-08-30

    Two experiments examined the effects of perirhinal cortex and hippocampal neurotoxic lesions on the retention of allocentric information. Perirhinal (Expt. 1) and hippocampal rats (Expt. 2) were trained on an allocentric task until they reached a performance equal to that of the control groups. Results showed that 24 days after acquisition, during a retraining period, only the hippocampal rats presented a deficit in retention. These results suggest that the perirhinal cortex and the hippocampus can be functionally dissociated in terms of their participation in the formation of long-term spatial memory. Also, the allocentric spatial memory functions of the hippocampus seem not to depend on their afferent connections with the perirhinal cortex.

  19. Electrical Stimulation Normalizes c-Fos Expression in the Deep Cerebellar Nuclei of Depressive-like Rats: Implication of Antidepressant Activity.

    PubMed

    Huguet, Gemma; Kadar, Elisabet; Temel, Yasin; Lim, Lee Wei

    2017-04-01

    The electrical stimulation of specific brain targets has been shown to induce striking antidepressant effects. Despite that recent data have indicated that cerebellum is involved in emotional regulation, the mechanisms by which stimulation improved mood-related behaviors in the cerebellum remained largely obscure. Here, we investigated the stimulation effects of the ventromedial prefrontal cortex (vmPFC), nucleus accumbens (NAc), and lateral habenular nucleus on the c-Fos neuronal activity in various deep cerebellar and vestibular nuclei using the unpredictable chronic mild stress (CMS) animal model of depression. Our results showed that stressed animals had increased number of c-Fos cells in the cerebellar dentate and fastigial nuclei, as well as in the spinal vestibular nucleus. To examine the stimulation effects, we found that vmPFC stimulation significantly decreased the c-Fos activity within the cerebellar fastigial nucleus as compared to the CMS sham. Similarly, there was also a reduction of c-Fos expression in the magnocellular part of the medial vestibular nucleus in vmPFC- and NAc core-stimulated animals when compared to the CMS sham. Correlational analyses showed that the anxiety measure of home-cage emergence escape latency was positively correlated with the c-Fos neuronal activity of the cerebellar fastigial and magnocellular and parvicellular parts of the interposed nuclei in CMS vmPFC-stimulated animals. Interestingly, there was a strong correlation among activation in these cerebellar nuclei, indicating that the antidepressant-like behaviors were possibly mediated by the vmPFC stimulation-induced remodeling within the forebrain-cerebellar neurocircuitry.

  20. Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

    NASA Astrophysics Data System (ADS)

    Donoghue, John P.; Sanes, Jerome N.

    1987-02-01

    We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

  1. Electrophysiology of regular firing cells in the rat perirhinal cortex.

    PubMed

    D'Antuono, M; Biagini, G; Tancredi, V; Avoli, M

    2001-01-01

    The electrophysiological properties of neurons in the rat perirhinal cortex were analyzed with intracellular recordings in an in vitro slice preparation. Cells included in this study (n = 59) had resting membrane potential (RMP) = -73.9 +/- 8.5 mV (mean +/- SD), action potential amplitude = 95.5 +/- 10.4 mV, input resistance = 36.1 +/- v 15.7 M omega, and time constant = 13.9 +/- 3.4 ms. When filled with neurobiotin (n = 27) they displayed a pyramidal shape with an apical dendrite and extensive basal dendritic tree. Injection of intracellular current pulses revealed: 1) a tetrodotoxin (TTX, 1 microM)-sensitive, inward rectification in the depolarizing direction (n = 6), and 2) a time- and voltage-dependent hyperpolarizing sag that was blocked by extracellular Cs+ (3 mM, n = 5) application. Prolonged (up to 3 s) depolarizing pulses made perirhinal cells discharge regular firing of fast action potentials that diminished over time in frequency and reached a steady level (i.e., adapted). Repetitive firing was followed by an afterhyperpolarization that was decreased, along with firing adaptation, by the Ca(2+)-channel blocker Co2+ (2 mM, n = 6). Action potential broadening became evident during repetitive firing. This behavior, which was more pronounced when larger pulses of depolarizing current were injected (and thus when repetitive firing attained higher rates), was markedly decreased by Co2+ application. Subthreshold membrane oscillations at 5-12 Hz became apparent when cells were depolarized by 10-20 mV from RMP, and action potential clusters appeared with further depolarization. Application of glutamatergic and GABAA receptor antagonists (n = 4), CO2+ (n = 6), or Cs+ (n = 5) did not prevent the occurrence of these oscillations that were abolished by TTX (n = 6). Our results show that pyramidal-like neurons in the perirhinal cortex are regular firing cells with electrophysiological features resembling those of other cortical pyramidal elements. The ability to

  2. Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

    PubMed

    Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

    2014-04-01

    Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

  3. Anterograde and Retrograde Amnesia of Place Discrimination in Retrosplenial Cortex and Hippocampal Lesioned Rats

    ERIC Educational Resources Information Center

    Haijima, Asahi; Ichitani, Yukio

    2008-01-01

    Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after…

  4. Protective potential of Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity and associated neuromuscular status in aged rats.

    PubMed

    Tripathi, S; Mahdi, A A; Hasan, M; Mitra, K; Mahdi, F

    2011-02-12

    The present study attempts to assess the comparative effects of Bacopa monniera, (40 mg/kg body weight) and donepezil (2.5 mg/kg b. wt) on aluminum (100 mg / kg b. wt. of AlCl3) mediated oxidative damage in the cerebellum of aged rats (24 months) along with the associated dysfunctioning of neuromuscular coordination and motor activity. A significant decrease in the activities of antioxidant enzymes and increased total reacting oxygen species, lipid and protein peroxidation products observed in aluminum exposed rats. We observed that treatment with B. monniera extract restored the altered antioxidant enzyme activities more, when compared with donepezil. However, acetylcholinesterase showed similar effect both in donepezil and B. monniera treated groups. The content of aluminum was increased in all experimental groups, however, iron content was found increased in all groups except the B. monniera treated groups. Moreover, aluminum treated groups of rats exhibited significant changes in behavioral profiles but these changes were in both B. monniera and donepezil treated groups. The light microscopic and ultrastructural studies revealed damaged Purkinje's neurons and altered granular cell layer along with the increased accumulation of lipofuscin granules in aluminum treated animals. These changes were quite less pronounced in B. monniera group than that of donepezil and this may be due to the reduction of excess iron content by B. monniera. On the basis of our results it may be concluded that Al may be linked with cerebellar degeneration and neuromuscular disorders while Bacopa monniera extract helps in reversing these changes.

  5. The effects of short-term enriched environment on capillaries of the middle-aged rat cortex.

    PubMed

    Qiu, Xuan; Li, Chen; Jiang, Rong; Chen, Lin; Huang, Chunxia; Yang, Shu; Lu, Wei; Shi, Xiaoyan; Zhao, Yuanyu; Gao, Yuan; Cheng, Guohua; Tang, Yong

    2011-11-14

    There has been no study investigating the effects of enriched environment on the capillaries of cortex with new stereological methods. In the present study, both 14 month female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in enriched environment and SE rats were reared in standard environment for 4 months. The effects of short-term enriched environment on the cortex volume and on the total volume, total length, total surface area and mean diameter of the capillaries in the cortex of mid-aged Sprague-Dawley rats were quantitatively investigated with immunohistochemistry technique and unbiased stereological methods. There were no significant differences in the cortex volume, the total length and total surface area of the capillaries in the cortex between EE rats and SE rats. The total volume of the capillaries in the cortex of female EE rats and male EE rats was significantly increased when compared to female SE rats and male SE rats. The mean diameter of the capillaries in the cortex of female EE rats was significantly decreased when compared to that in female SE rats, but there was no significant difference in the mean diameter of the capillaries in the cortex between male EE rats and male SE rats. The present results indicate that enriched environment had a positive effect on the capillaries in the cortex of middle-aged rats. The present study might provide an important morphological basis for searching the ethology strategy to delay the progress of brain aging in the future.

  6. Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.

    PubMed

    Tanaka, Satoshi; Yamada, Misa; Kitahara, Sari; Higuchi, Teruhiko; Honda, Kazuo; Kamijima, Kunitoshi; Yamada, Mitsuhiko

    2006-02-01

    Using expressed sequence tag (EST) analysis, we previously identified certain molecular machinery that mediates antidepressant effects. To date, several partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been isolated as ESTs from rat brain. In the present study, we identified two of the ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated increased neuroserpin mRNA expression in rat frontal cortex after chronic treatment with several classes of antidepressants, including imipramine, fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT), another therapeutic treatment for depression, also increased neuroserpin expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that is implicated in the regulation of synaptic plasticity, neuronal migration, and axogenesis in the central nervous system. In conclusion, our results support the hypothesis that neuroserpin-mediated plastic changes in frontal cortex may underlie the therapeutic action of antidepressants and ECT.

  7. Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

    PubMed Central

    Yarowsky, P J; Krueger, B K; Olson, C E; Clevinger, E C; Koos, R D

    1991-01-01

    The expression of mRNAs coding for the alpha subunit of rat brain and rat heart sodium channels has been studied in adult and neonatal rat cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). Rat brain sodium channel subtype I, II, IIA, and III sequences were simultaneously amplified in the same PCR using a single oligonucleotide primer pair matched to all four subtype sequences. Identification of each subtype-specific product was inferred from the appearance of unique fragments when the product was digested with specific restriction enzymes. By using this RT-PCR method, products arising from mRNAs for all four brain sodium channel subtypes were identified in RNA extracted from adult rat cerebral cortex. The predominant component was type IIA with lesser levels of types I, II, and III. In contrast, the type II and IIA sequences were the predominant RT-PCR products in neonatal rat cortex, with slightly lower levels of type III and undetectable levels of type I. Thus, from neonate to adult, type II mRNA levels decrease relative to type IIA levels. Using a similar approach, we detected mRNA coding for the rat heart sodium channel in neonatal and adult rat cerebral cortex and in adult rat heart. These results reveal that mRNAs coding for the heart sodium channel and all four previously sequenced rat brain sodium channel subtypes are expressed in cerebral cortex and that type II and IIA channels may be differentially regulated during development. Images PMID:1658783

  8. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  9. Accumulation of α-Synuclein in Cerebellar Purkinje Cells of Diabetic Rats and Its Potential Relationship with Inflammation and Oxidative Stress Markers

    PubMed Central

    Solmaz, Volkan; Eroglu, Hüseyin Avni; Aktuğ, Hüseyin; Erbaş, Oytun

    2017-01-01

    Objective. The present study was conducted to evaluate the relationship between plasma oxidative stress markers such as malondialdehyde (MDA) and glutathione (GSH), inflammatory marker pentraxin-3 (PTX3), and cerebellar accumulation of α-synuclein in streptozotocin- (STZ-) induced diabetes model in rats. Methods. Twelve rats were included in the study. Diabetes (n = 6) was induced with a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Diabetes was verified after 48 h by measuring blood glucose levels. Six rats served as controls. Following 8 weeks, rats were sacrificed for biochemical and immunohistochemical evaluation. Results. Plasma MDA levels were significantly higher in diabetic rats when compared with the control rats (p < 0.01), while plasma GSH levels were lower in the diabetic group than in the control group (p < 0.01). Also, plasma pentraxin-3 levels were statistically higher in diabetic rats than in the control rats (p < 0.01). The analysis of cerebellar α-synuclein immunohistochemistry showed a significant increase in α-synuclein immunoexpression in the diabetic group compared to the control group (p < 0.01). Conclusion. Due to increased inflammation and oxidative stress in the chronic period of hyperglycemia linked to diabetes, there may be α-synuclein accumulation in the cerebellum and the plasma PTX3 levels may be assessed as an important biomarker of this situation. PMID:28133547

  10. Fetal frontal cortex transplant (/sup 14/C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    SciTech Connect

    Sharp, F.R.; Gonzalez, M.F.

    1984-10-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The (/sup 14/C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional.

  11. [Cerebellar hypoplasias].

    PubMed

    Safronova, Marta Maia; Barbot, Clara; Resende Pereira, Jorge

    2010-01-01

    Cerebellar hypoplasias are cerebellar malformations with small but completely formed cerebellum. They can be divided in focal and in diffuse or generalized. It is sometimes difficult to make distinction between cerebellar atrophy (progressive condition) and hipoplasia (not progressive condition). Focal hypoplasias are restricted to one cerebellar hemisphere or to the vermis. Diffuse hypoplasias refer to both cerebellar hemispheres and vermis. If there is associated IVth ventricle enlargement, hypoplasias occur in the context of Dandy-Walker complex, a continuum of posterior fossa cystic anomalies. A revision of cerebellar hypoplasias and associated pathology is done, illustrated with 22 cases tha include focal and diffuse cerebellar hypoplasias, Dandy-Walker malformations and its variant, persistent Blake's pouch cyst, megacisterna magna, PEHO síndrome (progressive encephalopathy with oedema, hipsarrhythmia and optic atrophy), Joubert syndrome, congenital disorder of glycosylation type Ia, pontocerebellar hipoplasias Barth type I and II, diffuse subcortical heterotopia. The imaging finding of structural cerebellar anomalies frequently leads to diagnostic incertainty as the anomalies are mostly unspecific, implying an extenuating analytical and genetic workup. Their knowledge and classification may be useful to decide the patient adjusted laboratorial workup.

  12. Cortical connectivity maps reveal anatomically distinct areas in the parietal cortex of the rat.

    PubMed

    Wilber, Aaron A; Clark, Benjamin J; Demecha, Alexis J; Mesina, Lilia; Vos, Jessica M; McNaughton, Bruce L

    2014-01-01

    A central feature of theories of spatial navigation involves the representation of spatial relationships between objects in complex environments. The parietal cortex has long been linked to the processing of spatial visual information and recent evidence from single unit recording in rodents suggests a role for this region in encoding egocentric and world-centered frames. The rat parietal cortex can be subdivided into four distinct rostral-caudal and medial-lateral regions, which includes a zone previously characterized as secondary visual cortex. At present, very little is known regarding the relative connectivity of these parietal subdivisions. Thus, we set out to map the connectivity of the entire anterior-posterior and medial-lateral span of this region. To do this we used anterograde and retrograde tracers in conjunction with open source neuronal segmentation and tracer detection tools to generate whole brain connectivity maps of parietal inputs and outputs. Our present results show that inputs to the parietal cortex varied significantly along the medial-lateral, but not the rostral-caudal axis. Specifically, retrosplenial connectivity is greater medially, but connectivity with visual cortex, though generally sparse, is more significant laterally. Finally, based on connection density, the connectivity between parietal cortex and hippocampus is indirect and likely achieved largely via dysgranular retrosplenial cortex. Thus, similar to primates, the parietal cortex of rats exhibits a difference in connectivity along the medial-lateral axis, which may represent functionally distinct areas.

  13. Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats.

    PubMed

    Meneses, S; Galicia, O; Brailowsky, S

    1993-10-21

    It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.

  14. Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats.

    PubMed

    Zamudio-Bulcock, Paula A; Everett, Julie; Harteneck, Christian; Valenzuela, C Fernando

    2011-11-01

    The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. In this study, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells. We recently showed that PregS potentiates spontaneous glutamate release onto neonatal Purkinje cells during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.

  15. Paraneoplastic cerebellar degeneration with a circulating antibody against neurons and non-neuronal cells.

    PubMed

    Tomimoto, H; Brengman, J M; Yanagihara, T

    1993-01-01

    We describe a woman with paraneoplastic cerebellar degeneration associated with para-ovarian adenocarcinoma, who had a circulating antibody with a corresponding antigen not only in cerebellar Purkinje cells but also in neurons located in the molecular layer of the human and rat cerebellum. The antigen was also present in neurons in the cerebral cortex, brain stem, anterior horn cells, dorsal root ganglia, intestinal autonomic neurons, retinal ganglion cells, Schwann cells of the peripheral nerve and epithelial cells of the renal glomerulus in rats. Immunoelectron microscopy revealed immunoprecipitates in the smooth and rough endoplasmic reticulum and polyribosomes in human and rat cerebellar Purkinje cells and other neuronal cell bodies as well as Schwann cells of the peripheral nerve. Even though patients with this disorder manifest primarily with cerebellar and some extracerebellar signs, the antigen also exists in many neurons other than cerebellar Purkinje cells and even in non-neuronal cells. The clinicopathologic significance of the observed immunologic reaction in diverse neurons remains to be determined.

  16. Inhibition of the amygdala central nucleus by stimulation of cerebellar output in rats: a putative mechanism for extinction of the conditioned fear response.

    PubMed

    Magal, Ari; Mintz, Matti

    2014-11-01

    The amygdala and the cerebellum serve two distinctively different functions. The amygdala plays a role in the expression of emotional information, whereas the cerebellum is involved in the timing of discrete motor responses. Interaction between these two systems is the basis of the two-stage theory of learning, according to which an encounter with a challenging event triggers fast classical conditioning of fear-conditioned responses in the amygdala and slow conditioning of motor-conditioned responses in the cerebellum. A third stage was hypothesised when an apparent interaction between amygdala and cerebellar associative plasticity was observed: an adaptive rate of cerebellum-dependent motor-conditioned responses was associated with a decrease in amygdala-dependent fear-conditioned responses, and was interpreted as extinction of amygdala-related fear-conditioned responses by the cerebellar output. To explore this hypothesis, we mimicked some components of classical eyeblink conditioning in anesthetised rats by applying an aversive periorbital pulse as an unconditioned stimulus and a train of pulses to the cerebellar output nuclei as a cerebellar neuronal-conditioned response. The central amygdala multiple unit response to the periorbital pulse was measured with or without a preceding train to the cerebellar output nuclei. The results showed that activation of the cerebellar output nuclei prior to periorbital stimulation produced diverse patterns of inhibition of the amygdala response to the periorbital aversive stimulus, depending upon the nucleus stimulated, the laterality of the nucleus stimulated, and the stimulus interval used. These results provide a putative extinction mechanism of learned fear behavior, and could have implications for the treatment of pathologies involving abnormal fear responses by using motor training as therapy.

  17. Morphology of Pyramidal Neurons in the Rat Prefrontal Cortex: Lateralized Dendritic Remodeling by Chronic Stress

    PubMed Central

    Perez-Cruz, Claudia; Müller-Keuker, Jeanine I. H.; Heilbronner, Urs; Fuchs, Eberhard; Flügge, Gabriele

    2007-01-01

    The prefrontal cortex (PFC) plays an important role in the stress response. We filled pyramidal neurons in PFC layer III with neurobiotin and analyzed dendrites in rats submitted to chronic restraint stress and in controls. In the right prelimbic cortex (PL) of controls, apical and distal dendrites were longer than in the left PL. Stress reduced the total length of apical dendrites in right PL and abolished the hemispheric difference. In right infralimbic cortex (IL) of controls, proximal apical dendrites were longer than in left IL, and stress eliminated this hemispheric difference. No hemispheric difference was detected in anterior cingulate cortex (ACx) of controls, but stress reduced apical dendritic length in left ACx. These data demonstrate interhemispheric differences in the morphology of pyramidal neurons in PL and IL of control rats and selective effects of stress on the right hemisphere. In contrast, stress reduced dendritic length in the left ACx. PMID:18253468

  18. Network mechanisms of spindle-burst oscillations in the neonatal rat barrel cortex in vivo.

    PubMed

    Minlebaev, Marat; Ben-Ari, Yehezkel; Khazipov, Rustem

    2007-01-01

    Early in development, cortical networks generate particular patterns of activity that participate in cortical development. The dominant pattern of electrical activity in the neonatal rat neocortex in vivo is a spatially confined spindle-burst. Here, we studied network mechanisms of generation of spindle-bursts in the barrel cortex of neonatal rats using a superfused cortex preparation in vivo. Both spontaneous and sensory-evoked spindle-bursts were present in the superfused barrel cortex. Pharmacological analysis revealed that spindle-bursts are driven by glutamatergic synapses with a major contribution of AMPA/kainate receptors, but slight participation of NMDA receptors and gap junctions. Although GABAergic synapses contributed minimally to the pacing the rhythm of spindle-burst oscillations, surround GABAergic inhibition appeared to be crucial for their compartmentalization. We propose that local spindle-burst oscillations, driven by glutamatergic synapses and spatially confined by GABAergic synapses, contribute to the development of barrel cortex during the critical period of developmental plasticity.

  19. Ultrastructure of neurons and interneuronal connections in the sensomotor cortex of progeny of alcohol-addicted rats

    SciTech Connect

    Popova, E.N.

    1985-05-01

    This paper studies the ultrastructure of neurons and interneuronal connections in the sensomotor cortex of the progeny of alcohol-addicted rats. Experiments were carried out on 12 female and four male albino rats; they were given alcohol solutions for 4 months and then mated. The female rats continued to ingest alcohol until the young rats acquired vision. The sensomotor cortex of experimental young rats aged 21 and 30 days and of intact animals of the same age was investigated; the sections were stained with uranyl acetate and studied. It is shown that alcoholic intoxication of females and males causes significant disturbances of the structural organization of the sensomotor cortex in the progeny.

  20. Anti-Yo antibody uptake and interaction with its intracellular target antigen causes Purkinje cell death in rat cerebellar slice cultures: a possible mechanism for paraneoplastic cerebellar degeneration in humans with gynecological or breast cancers.

    PubMed

    Greenlee, John E; Clawson, Susan A; Hill, Kenneth E; Wood, Blair; Clardy, Stacey L; Tsunoda, Ikuo; Carlson, Noel G

    2015-01-01

    Anti-Yo antibodies are immunoglobulin G (IgG) autoantibodies reactive with a 62 kDa Purkinje cell cytoplasmic protein. These antibodies are closely associated with paraneoplastic cerebellar degeneration in the setting of gynecological and breast malignancies. We have previously demonstrated that incubation of rat cerebellar slice cultures with patient sera and cerebrospinal fluid containing anti-Yo antibodies resulted in Purkinje cell death. The present study addressed three fundamental questions regarding the role of anti-Yo antibodies in disease pathogenesis: 1) Whether the Purkinje cell cytotoxicity required binding of anti-Yo antibody to its intraneuronal 62 kDa target antigen; 2) whether Purkinje cell death might be initiated by antibody-dependent cellular cytotoxicity rather than intracellular antibody binding; and 3) whether Purkinje cell death might simply be a more general result of intracellular antibody accumulation, rather than of specific antibody-antigen interaction. In our study, incubation of rat cerebellar slice cultures with anti-Yo IgG resulted in intracellular antibody binding, and cell death. Infiltration of the Purkinje cell layer by cells of macrophage/microglia lineage was not observed until extensive cell death was already present. Adsorption of anti-Yo IgG with its 62 kDa target antigen abolished both antibody accumulation and cytotoxicity. Antibodies to other intracellular Purkinje cell proteins were also taken up by Purkinje cells and accumulated intracellularly; these included calbindin, calmodulin, PCP-2, and patient anti-Purkinje cell antibodies not reactive with the 62 kDa Yo antigen. However, intracellular accumulation of these antibodies did not affect Purkinje cell viability. The present study is the first to demonstrate that anti-Yo antibodies cause Purkinje cell death by binding to the intracellular 62 kDa Yo antigen. Anti-Yo antibody cytotoxicity did not involve other antibodies or factors present in patient serum and was not

  1. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

    PubMed Central

    Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (<1 year) when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

  2. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex.

    PubMed

    Pinto, Joshua G A; Jones, David G; Williams, C Kate; Murphy, Kathryn M

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (<1 year) when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

  3. Cerebellar Circuit Mechanisms Which Accompany Coordinated Limb Trajectory Patterns in the Rat: Use of a Model of Spontaneous Changes in Limb Coordination

    DTIC Science & Technology

    1994-08-01

    cerebelar circuit are observed during tests of limb coordation? For thti and the following aims, chronically Implanted microwires wil simultaneously...implanted microwires to allow up to 23 indvidual single units to be discaixidated from one rat. DVscharge can that be assessed during treadnall locomotor...cerebellar circuits, Sympna•um: Hormonal and non-hormonal effects of steroids in the CNS (I. Olsetn, chair), Albuquerque, New Mexico, March. 1994. 7. Seminar presentatinn: NYU Medical School, Dept. of Physiolog April 1994. 6

  4. Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer

    PubMed Central

    Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

    2016-01-01

    Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). Hmax (H-wave maximum amplitude)/Mmax (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential

  5. Callosal projections in rat somatosensory cortex are altered by early removal of afferent input.

    PubMed Central

    Koralek, K A; Killackey, H P

    1990-01-01

    During the first postnatal week, the distribution of callosal projection neurons in the rat somatosensory cortex changes from a uniform to a discontinuous pattern. To determine if this change is influenced by afferent inputs to the somatosensory cortex, the effect of both early unilateral infraorbital nerve section and unilateral removal of the dorsal thalamus on the distribution of callosal projections in rat somatosensory cortex was examined. One month after either of the above manipulations at birth, the tangential distribution of callosal projections in the somatosensory cortex was examined using the combined retrograde and anterograde transport of horseradish peroxidase. Both manipulations alter the distribution of callosal projection neurons and terminations in the somatosensory cortex. After infraorbital nerve section, the distribution of callosal projections is altered in the contralateral primary somatosensory cortex. The abnormalities observed are consistent with the altered distribution of thalamocortical projections. In addition, consistent abnormalities were observed in the pattern of callosal projections of the second somatosensory area of both hemispheres. Most notably, they are absent in a portion of the region that contains the representation of the mystacial vibrissae and sinus hairs in this area. Thalamic ablation resulted in highly aberrant patterns of callosal projections in the somatosensory cortex on the operated side, where abnormal bands and clusters of callosal projections were observed in apparently random locations. These results are interpreted as evidence that both peripheral and central inputs influence the maturational changes in the distribution of callosal projection neurons. Images PMID:2304906

  6. Ethanol intake-induced apoptosis in glial cells and axonal disorders in the cerebellar white matter of UChA rats (voluntary ethanol consumers).

    PubMed

    Martinez, Marcelo; Sauce, Rafael; Oliveira, Suelen Alves; de Almeida Chuffa, Luiz Gustavo; Stefanini, Maíra Aparecida; Lizarte Neto, Fermino Sanches; Takase, Luiz Fernando; Tirapelli, Luiz Fernando; Martinez, Francisco Eduardo

    2015-08-01

    Ethanol intake may cause alterations in cellular metabolism altering motricity, learning and cognition. The cerebellum is one of the most susceptible organs to ethanol-related disorders during development, and is associated with oxidative stress-induced apoptosis being crucial for pathogenic consequences. The UChA variety is a special strain of Wistar rat genetically selected and represents a rare model for the studies related to genetic, biochemical, physiological, nutritional, and pharmacological effects of ethanol. We evaluated the structure and apoptosis in the cerebellar white matter of UChA rats. There were two groups of 09 rats: a control group that did not consume ethanol, and an experimental group of UChA rats that consumed ethanol at 10% (v/v) (<2 g ethanol/kg body weight/day). At 120 days old, rats were anaesthetized followed by decapitation, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for Caspase-3 and XIAP and transmission electron microscopy (TEM). The UChA group showed more glial cells immunoreactive for caspase-3 and less for XIAP than control group. Alcohol consumption affected myelin integrity. Severe ultrastructural damages in UChA group were observed such as disruption of the myelin sheath, disorganization and deformation of its components, and an increase in the interaxonal spaces. In conclusion, our data demonstrated that ethanol induced apoptosis in the glial cells and promoted an intense change in the myelin sheath of UChA rats, which may cause functional disorders.

  7. Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons.

    PubMed

    Zhu, W J; Wang, J F; Corsi, L; Vicini, S

    1998-09-15

    1. We investigated La3+ effects on recombinant and native gamma-aminobutyric acid A (GABAA) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neurons of rat cerebellar slices. 2. Rapid desensitization of currents elicited by 200 ms pulses of 1 mM GABA to small lifted cells transfected with alpha1beta3gamma2 cDNAs was greatly decreased by the coapplication of 100 microM LaCl3. 3. GABA responses were unaffected when coapplication lasted only 2 ms. In contrast, with LaCl3 pre-perfusion, a significant slowing of deactivation in response to 2 ms applications was observed. LaCl3 pre-perfusion also prolonged the duration of responses to 20 mM taurine. 4. Outside-out patches excised from cells transfected with alpha1beta3gamma2 subunit cDNAs were briefly exposed to a saturating concentration of GABA, eliciting a transient activation of single channel currents with a main conductance of 30 pS. Opening and burst durations increased by pre-equilibration of patches with LaCl3. 5. LaCl3 depressed the peak amplitude without affecting the slow deactivation and desensitization of GABA responses in cells transfected with alpha6beta3gamma2 and alpha6beta3delta cDNAs. No significant difference in La3+ modulation of GABA-gated currents was observed between alpha1beta3gamma2 and alpha1beta3delta receptors. 6. The effects of LaCl3 on deactivation and desensitization of GABA responses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with alpha1beta3gamma2 cDNAs. In addition, La3+ clearly prolonged the spontaneous IPSC time course without changing the amplitude. 7. Our results indicate that La3+ has a dual action on GABA-gated currents: it decreases desensitization and increases channel opening duration. These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.

  8. The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function.

    PubMed

    Kealy, John; Commins, Sean

    2011-04-01

    The perirhinal cortex is located in a pivotal position to influence the flow of information into and out of the hippocampal formation. In this review, we examine the anatomical, physiological and functional properties of the rat perirhinal cortex. Firstly, we review the properties of the perirhinal cortex itself, we describe how it can be separated into two distinct subregions and consider how it differs from other neighbouring regions in terms of cell type, cellular organisation and its afferent and efferent projections. We review the forms of neurotransmission present in the perirhinal cortex and the morphological, electrophysiological and plastic properties of its neurons. Secondly, we review the perirhinal cortex in the context of its connections with other brain areas; focussing on the projections to cortical, subcortical and hippocampal/parahippocampal regions. Particular attention is paid the anatomical and electrophysiological properties of these projections. Thirdly, we review the main functions of the perirhinal cortex; its roles in perception, recognition memory, spatial and contextual memory and fear conditioning are explored. Finally, we discuss the idea of anatomical, electrophysiological and functional segregation within the perirhinal cortex itself and as part of a hippocampal-parahippocampal network and suggest that understanding this segregation is of critical importance in understanding the role and contributions made by the perirhinal cortex in general.

  9. Hypothalamo‑hypophysial system in rats with autotransplantation of the adrenal cortex.

    PubMed

    Takizawa, Nae; Tanaka, Susumu; Oe, Souichi; Koike, Taro; Matsuda, Tadashi; Yamada, Hisao

    2017-03-24

    Patients with bilateral pheochromocytoma often require an adrenalectomy. Autotransplantation of the adrenal cortex is an alternative therapy that could potentially be performed instead of receiving glucocorticoid replacement following adrenalectomy. Adrenal cortex autotransplantation aims to avoid the side effects of long‑term steroid treatment and adrenal insufficiency. Although the function of the hypothalamo‑hypophysial system is critical for patients who have undergone adrenal cortex autotransplantation, the details of that system, with the exception of adrenocorticotropic hormone in the subjects with adrenal autotransplantation, have been overlooked for a long time. To clarify the precise effect of adrenal autotransplantation on the pituitary gland and hypothalamus, the current study examined the gene expression of hormones produced from the hypothalamus and pituitary gland. Bilateral adrenalectomy and adrenal autotransplantation were performed in 8 to 9‑week‑old male rats. The hypothalamus and pituitary tissues were collected at 4 weeks after surgery. Transcriptional regulation of hypothalamic and pituitary hormones was subsequently examined by reverse transcription‑quantitative polymerase chain reaction. Proopiomelanocortin, glycoprotein hormone α polypeptide, and thyroid stimulating hormone β were significantly elevated in the pituitary gland of autotransplanted rats when compared with sham‑operated rats. In addition, there were significant differences in the levels of corticotropin releasing hormone receptor 1 (Crhr1), Crhr2, nuclear receptor subfamily 3 group C member 1 and thyrotropin releasing hormone receptor between the sham‑operated rats and autotransplanted rats in the pituitary gland. In the hypothalamus, corticotropin releasing hormone and urocortin 2 mRNA was significantly upregulated in autotransplanted rats compared with sham‑operated rats. The authors identified significant alterations in the function of not only the

  10. Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

    PubMed

    Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

    2016-11-09

    Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

  11. Differential expression of two-pore domain potassium channels in rat cerebellar granule neurons.

    PubMed

    Burgos, Paulina; Zúñiga, Rafael; Domínguez, Pedro; Delgado-López, Fernando; Plant, Leigh D; Zúñiga, Leandro

    2014-10-31

    Two pore domain potassium (K2P) channels are mostly present in the central nervous system (CNS) where they play important roles in modulating neuronal excitability. K2P channels give rise to background K(+) currents (IKSO) a key component in setting and maintaining the resting membrane potential in excitable cells. Here, we studied the expression and relative abundances of K2P channels in cerebellar granule neurons (CGNs), combining molecular biology, electrophysiology and immunologic techniques. The CGN IKSO was very sensitive to external pH, as previously reported. Quantitative determination of mRNA expression level demonstrated the existence of an accumulation pattern of transcripts in CGN that encode K2P9>K2P1>K2P3>K2P18>K2P2=K2P10>K2P4>K2P5 subunits. The presence of the major K2P subunits expressed was then confirmed by Western blot and immunofluorescence analysis, demonstrating robust expression of K2P1 (TWIK-1), K2P3 (TASK-1), K2P9 (TASK-3) and K2P18 (TRESK) channel protein. Based, on these results, it is concluded that K2P1, -3, -9 and -18 subunits represent the majority component of IKSO current in CGN.

  12. Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells.

    PubMed

    Jiménez, Andrés; Jordà, Elvira G; Verdaguer, Ester; Pubill, David; Sureda, Francesc X; Canudas, Anna M; Escubedo, Elena; Camarasa, Jordi; Camins, Antoni; Pallàs, Mercè

    2004-04-15

    The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 microM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 microM) but not by 10 microM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using alpha-tocopherol (1-15 microM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors.

  13. Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin.

    PubMed

    Martina, Marco; Metz, Alexia E; Bean, Bruce P

    2007-01-01

    We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10-90% activation in about 400 mus at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 mus near -80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium current evoked by action potential waveforms was inhibited nearly completely. The mechanism of inhibition by BDS-I involves slowing of activation rather than total channel block, consistent with the effects described in cloned Kv3-family channels and this explains the dramatically different effects on currents evoked by short spikes versus voltage steps. As predicted from this mechanism, the effects of toxin on spike width were relatively modest (broadening by roughly 25%). These results show that BDS-I-sensitive channels with ultrafast activation and deactivation kinetics carry virtually all of the voltage-dependent potassium current underlying repolarization during normal Purkinje cell spikes.

  14. Neurotoxicity of the pentabrominated diphenyl ether mixture, DE-71, and hexabromocyclododecane (HBCD) in rat cerebellar granule cells in vitro.

    PubMed

    Reistad, Trine; Fonnum, Frode; Mariussen, Espen

    2006-11-01

    Polybrominated diphenyl ethers (PBDE) and hexabromocyclododecane (HBCD) are compounds used as additive flame retardants in plastics, electronic equipment, and textiles. The aim of the present study was to investigate the in vitro effects of the pentabrominated diphenyl ether mixture, DE-71, and HBCD on cerebellar granule cells (CGC). Both DE-71 and HBCD induced death of CGC in low micromolar concentrations. The NMDA receptor antagonist MK801 (3 microM), and the antioxidant alpha-tocopherol (50 microM) significantly reduced the cell death. Incubation of the compounds together with the rat liver post-mitochondrial (S9) fraction reduced cell death by 58 and 64% for DE-71 and HBCD, respectively. No ROS formation and no elevation in intracellular calcium were observed. We further demonstrated apoptotic morphology (Hoechst straining) after exposure to low levels of the two brominated flame retardants and signs of DNA laddering were found after DE-71 exposure. However, other hallmarks of apoptosis, like caspase activity, were absent indicating an atypical form of apoptosis induced by DE-71. After intraperitoneal injection of the two compounds both DE-71 and HBCD were found in significant amounts in brain (559 +/- 194 and 49 +/- 13 microg/kg, respectively) and liver (4,010 +/- 2,437 and 1,248 +/- 505 microg/kg, respectively) 72 h after injection. Our results indicate that the lower brominated PBDEs have a higher potency of bioaccumulation than HBCD, and that both compounds have a neurotoxic potential in vitro.

  15. Maternal marginal iodine deficiency limits dendritic growth of cerebellar purkinje cells in rat offspring by NF-κB signaling and MAP1B.

    PubMed

    Yu, Ye; Dong, Jing; Wang, Yuan; Wang, Yi; Min, Hui; Shan, Zhongyan; Teng, Weiping; Chen, Jie

    2017-04-01

    Iodine deficiency (ID) during early pregnancy had an adverse effect on children's psychomotor and motor function. It is worth noting that maternal marginal ID tends to be a common public health problem. Whether marginal ID potentially had adverse effects on the development of cerebellum and the underlying mechanisms remain unclear. Therefore, our aim was to study the effects of marginal ID on the dendritic growth in filial cerebellar Purkinje cells (PCs) and the underlying mechanism. In the present study, we established Wistar rat models by feeding dam rats with a diet deficient in iodine and deionized water supplemented with potassium iodide. We examined the total dendritic length using immunofluorescence, and Western blot analysis was conducted to investigate the activity of nuclear factor-κB (NF-κB) signaling and microtubule-associated protein 1B (MAP1B). Our results showed that marginal ID reduced the total dendritic length of cerebellar PCs, slightly down-regulated the activity of NF-κB signaling and decreased MAP1B in cerebellar PCs on postnatal day (PN) 7, PN14, and PN21. Our study may support the hypothesis that decreased T4 induced by marginal ID limits PCs dendritic growth, which may involve in the disturbance of NF-κB signaling and MAP1B on the cerebellum. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1241-1251, 2017.

  16. Single course of antenatal betamethasone produces delayed changes in morphology and calbindin-D28k expression in a rat's cerebellar Purkinje cells.

    PubMed

    Pascual, Rodrigo; Valencia, Martina; Larrea, Sebastián; Bustamante, Carlos

    2014-01-01

    In the current study, we analyzed the impact of antenatal betamethasone on macroscopic cerebellar development, Purkinje cell morphology and the expression of the neuroprotective protein calbindin-D28k. Pregnant rats (Sprague-Dawley) were randomly divided into two experimental groups: control (CONT) and betamethasone-treated (BET). At gestational day 20 (G20), BET dams were subcutaneously injected with a solution of 0.17 mg kg⁻¹ of betamethasone, while CONT animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CONT offspring were behaviorally evaluated, and the cerebella were histologically and immunohistochemically processed. Animals that were prenatally treated with a single course of betamethasone exhibited long-lasting behavioral changes consistent with anxiety-like behavior in the open-field test, together with (1) reduced cerebellar weight and volume, (2) Purkinje cell dendritic atrophy, and (3) an overexpression of calbindin-D28k. The current results indicate that an experimental single course of betamethasone in pregnant rats produces long-lasting anxiety-like behaviors, together with macroscopic and microscopic cerebellar alterations.

  17. No changes in cerebral microcirculatory parameters in rat during local cortex exposure to microwaves.

    PubMed

    Masuda, Hiroshi; Hirota, Shogo; Ushiyama, Akira; Hirata, Akimasa; Arima, Takuji; Watanabe, Hiroshi; Wake, Kanako; Watanabe, Soichi; Taki, Masao; Nagai, Akiko; Ohkubo, Chiyoji

    2015-01-01

    The aim of this study was to determine whether cerebral microcirculatory parameters in rats were modified during local cortex exposure to a radiofrequency electromagnetic field (RF) under non-thermal conditions. The cortex tissue targeted was locally exposed to 1439 MHz RF using a figure-8 loop antenna at an averaged specific absorption rate of 2.0 W/kg in the target area for 50 min. Three microcirculatory parameters related to cerebral inflammation were measured by the cranial window method in real-time under RF exposure. No extravasation of intravenously injected fluorescent dye was observed during RF exposure. There was no significant difference either in pial venule blood flow velocity or diameter between exposed and sham-exposed rats. Histological evaluation for the brain immediately after RF exposure did not reveal any serum albumin leakage sites or degenerate neurons. These findings suggest that no dynamic changes occurred in cerebral microcirculation even during local cortex exposure under these conditions.

  18. Interhemispheric modulation of sensory transmission in the primary somatosensory cortex of rats.

    PubMed

    Shin, H C; Won, C K; Jung, S C; Oh, S; Park, S; Sohn, J H

    1997-07-18

    Single unit responses of the primary somatosensory (SI) cortical neurons to the stimulation of the forepaw single digit were monitored in anesthetized rats before and after subcutaneous injection of lidocaine to an ipsilateral homologous receptive field (IHRF). Quantitative determination of the temporal changes of afferent sensory transmission was done by analyzing poststimulus time histograms of unit responses. Temporary deafferentation to the IHRF induced immediate, but reversible suppression of afferent sensory transmission in the SI cortex and this suppression lasts up to 35 min post-deafferentation period (during 10-15 min, -21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of afferent inflow from the digit to the SI cortex may exert interhemispheric modulation of afferent sensory transmission in the opposite somatosensory cortex of anesthetized rats.

  19. Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells.

    PubMed

    Wawrzeńczyk, A; Nałecz, K A; Nałecz, M J

    1995-06-01

    Acetylcholine synthesis from radiolabelled glucose was monitored in cerebral cortex cells isolated from brains of suckling and adult rats. Acetylcholine synthesis was found much higher in suckling animals, both in the absence and presence of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) inhibitor, paraoxon. Together with choline (20 microM), carnitine was found to stimulate acetylcholine synthesis in a synergistic way in cortex cells from adult rats (18%). Choline, however, was incapable of reversing an inhibitory effect exerted by carnitine on acetylcholine synthesis in cortex cells from suckling animals. Distribution of carnitine derivatives was found significantly different in the cells from young and old animals, the content of acetylcarnitine decreased with age with a corresponding increase of free carnitine. The observed differences in carnitine effect on acetylcholine synthesis suggested that high acetylcarnitine in cells capable of beta-oxidation might be correlated with the lower level of acetylcholine synthesis.

  20. Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

    ERIC Educational Resources Information Center

    Baker, Phillip M.; Ragozzino, Michael E.

    2014-01-01

    Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

  1. Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla.

    PubMed Central

    Ingelfinger, J R; Pratt, R E; Ellison, K; Dzau, V J

    1986-01-01

    Rat liver angiotensinogen cDNA (pRang 3) and mouse renin cDNA (pDD-1D2) were used to identify angiotensinogen and renin mRNA sequences in rat kidney cortex and medulla in rats on high and low salt diet. Angiotensinogen mRNA sequences were present in renal cortex and medulla in apparently equal proportions, whereas renin mRNA sequences were found primarily in renal cortex. Average relative signal of rat liver to whole kidney angiotensinogen mRNA was 100:3. Densitometric analysis of Northern blots demonstrated that renal cortical angiotensinogen mRNA concentrations increased 3.5-fold (P less than 0.001) and medulla, 1.5-fold (P less than 0.005) on low sodium compared with high sodium diet, whereas renal cortex renin mRNA levels increased 6.8-fold (P less than 0.0005). Dietary sodium did not significantly influence liver angiotensinogen mRNA levels. These findings provide evidence for sodium regulation of renal renin and angiotensinogen mRNA expressions, which supports potential existence of an intrarenally regulated RAS and suggest that different factors regulate renal and hepatic angiotensinogen. Images PMID:3533999

  2. A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

    PubMed Central

    Hogri, Roni; Bamford, Simeon A.; Taub, Aryeh H.; Magal, Ari; Giudice, Paolo Del; Mintz, Matti

    2015-01-01

    Neuroprostheses could potentially recover functions lost due to neural damage. Typical neuroprostheses connect an intact brain with the external environment, thus replacing damaged sensory or motor pathways. Recently, closed-loop neuroprostheses, bidirectionally interfaced with the brain, have begun to emerge, offering an opportunity to substitute malfunctioning brain structures. In this proof-of-concept study, we demonstrate a neuro-inspired model-based approach to neuroprostheses. A VLSI chip was designed to implement essential cerebellar synaptic plasticity rules, and was interfaced with cerebellar input and output nuclei in real time, thus reproducing cerebellum-dependent learning in anesthetized rats. Such a model-based approach does not require prior system identification, allowing for de novo experience-based learning in the brain-chip hybrid, with potential clinical advantages and limitations when compared to existing parametric “black box” models. PMID:25677559

  3. Effects of ammonia on high affinity glutamate uptake and glutamate transporter EAAT3 expression in cultured rat cerebellar granule cells.

    PubMed

    Chan, Helen; Zwingmann, Claudia; Pannunzio, Marc; Butterworth, Roger F

    2003-07-01

    Increased levels of extracellular glutamate are a consistent feature of hepatic encephalopathy (HE) associated with liver failure and other hyperammonemic pathologies. Reduction of glutamate uptake has been described in ammonia-exposed cultured astrocytes, synaptosomes, and in animal models of hyperammonemia. In the present study, we examine the effects of pathophysiological concentrations of ammonia on D-aspartate (a non-metabolizable analog of glutamate) uptake by cultured rat cerebellar granule neurons. Exposure of these cells to ammonia resulted in time-dependent (24% reduction at 24h and 60% reduction at 5 days, P<0.001) and dose-dependent (21, 37, and 57% reduction at 1, 2.5, and 5mM for 5 days, P<0.01) suppression of D-aspartate uptake. Kinetic analyses revealed significant decreases in the velocity of uptake (V(max)) (37% decrease at 2.5mM NH(4)Cl, P<0.05 and 52% decrease at 5mM NH(4)Cl, P<0.001) as well as significant reductions in K(m) values (25% reduction at 2.5mM NH(4)Cl, P<0.05 and 45% reduction at 5mM NH(4)Cl, P<0.001). Western blotting, on the other hand, showed no significant changes in the neuronal glutamate transporter EAAC1/EAAT3 protein, the only glutamate transporter currently known to be expressed by these cells. In addition, 1H combined with 13C-NMR spectroscopy studies using the stable isotope [1-13C]-glucose demonstrated a significant increase in intracellular glutamate levels derived from the oxidative metabolism of glucose, rather than from the deamidation of exogenous glutamine in cultured granule neurons exposed to ammonia. The present study provides evidence that the effects of ammonia on glutamate uptake are not solely an astrocytic phenomenon and that unlike the astrocytic glutamate transporter counterpart, EAAT3 protein expression in cultured cerebellar granule cells is not down-regulated when exposed to ammonia. Decrease of glutamate uptake in these cellular preparations may afford an additional regulatory mechanism aimed at

  4. Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats

    PubMed Central

    Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

    2016-01-01

    Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session. PMID:27314672

  5. Chronic In Vivo Imaging of Ponto-Cerebellar Mossy Fibers Reveals Morphological Stability during Whisker Sensory Manipulation in the Adult Rat123

    PubMed Central

    Rylkova, Daria; Crank, Aidan R.

    2015-01-01

    Abstract The cerebellum receives extensive disynaptic input from the neocortex via the basal pontine nuclei, the neurons of which send mossy fiber (MF) axons to the granule cell layer of the contralateral cerebellar hemisphere. Although this cortico-cerebellar circuit has been implicated in tasks such as sensory discrimination and motor learning, little is known about the potential role of MF morphological plasticity in the function of the cerebellar granule cell layer. To address this issue, we labeled MFs with EGFP via viral infection of the basal pons in adult rats and performed in vivo two-photon imaging of MFs in Crus I/II of the cerebellar hemisphere over a period of several weeks. Following the acquisition of baseline images, animals were housed in control, enriched, or deprived sensory environments. Morphological dynamics were assessed by tracing MF axons and their terminals, and by tracking the stability of filopodia arising from MF terminal rosettes. MF axons and terminals were found to be remarkably stable. Parameters derived neither from measurements of axonal arbor geometry nor from the morphology of individual rosettes and their filopodial extensions significantly changed under control conditions over 4 weeks of imaging. Increasing whisker stimulation by manipulating the sensory environment or decreasing such stimulation by whisker trimming also failed to alter MF structure. Our studies indicate that pontine MF axons projecting to Crus I/II in adult rats do not undergo significant structural rearrangements over the course of weeks, and that this stability is not altered by the sustained manipulation of whisker sensorimotor experience. PMID:26693178

  6. Higher susceptibility of cerebral cortex and striatum to sulfite neurotoxicity in sulfite oxidase-deficient rats.

    PubMed

    Grings, Mateus; Moura, Alana Pimentel; Parmeggiani, Belisa; Motta, Marcela Moreira; Boldrini, Rafael Mello; August, Pauline Maciel; Matté, Cristiane; Wyse, Angela T S; Wajner, Moacir; Leipnitz, Guilhian

    2016-11-01

    Patients affected by sulfite oxidase (SO) deficiency present severe seizures early in infancy and progressive neurological damage, as well as tissue accumulation of sulfite, thiosulfate and S-sulfocysteine. Since the pathomechanisms involved in the neuropathology of SO deficiency are still poorly established, we evaluated the effects of sulfite on redox homeostasis and bioenergetics in cerebral cortex, striatum, cerebellum and hippocampus of rats with chemically induced SO deficiency. The deficiency was induced in 21-day-old rats by adding 200ppm of tungsten, a molybdenum competitor, in their drinking water for 9weeks. Sulfite (70mg/kg/day) was also administered through the drinking water from the third week of tungsten supplementation until the end of the treatment. Sulfite decreased reduced glutathione concentrations and the activities of glutathione reductase and glutathione S-transferase (GST) in cerebral cortex and of GST in cerebellum of SO-deficient rats. Moreover, sulfite increased the activities of complexes II and II-III in striatum and of complex II in hippocampus, but reduced the activity of complex IV in striatum of SO-deficient rats. Sulfite also decreased the mitochondrial membrane potential in cerebral cortex and striatum, whereas it had no effect on mitochondrial mass in any encephalic tissue evaluated. Finally, sulfite inhibited the activities of malate and glutamate dehydrogenase in cerebral cortex of SO-deficient rats. Taken together, our findings indicate that cerebral cortex and striatum are more vulnerable to sulfite-induced toxicity than cerebellum and hippocampus. It is presumed that these pathomechanisms may contribute to the pathophysiology of neurological damage found in patients affected by SO deficiency.

  7. Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex

    PubMed Central

    Vinken, Kasper; Van den Bergh, Gert; Vermaercke, Ben; Op de Beeck, Hans P.

    2016-01-01

    In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex. PMID:27146315

  8. Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.

    PubMed

    Guasti, Leonardo; Paul, Alex; Laufer, Ed; King, Peter

    2011-04-10

    Sonic hedgehog signaling was recently demonstrated to play an important role in murine adrenal cortex development. The organization of the rat adrenal differs from that of the mouse, with the zona glomerulosa and zona fasciculata separated by an undifferentiated zone in the rat, but not in the mouse. In the present study we aimed to determine the mRNA expression patterns of Sonic hedgehog and the hedgehog signaling pathway components Patched-1 and Gli1 in the developing and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal-receiving cells were localized in the overlying capsule mesenchyme. Using combined in situ hybridization and immunohistochemistry we found that the cells expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus Sonic hedgehog expression defines one cell population of the undifferentiated zone.

  9. [Memory transfer in cerebellar motor learning].

    PubMed

    Nagao, Soichi

    2012-01-01

    Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

  10. Enhanced synaptic responses in the piriform cortex associated with sexual stimulation in the male rat.

    PubMed

    Pfaus, J G; Tse, T L M; Werk, C M; Chanda, M L; Leblonde, A; Harbour, V L; Chapman, C A

    2009-12-29

    Male rats that copulate to ejaculation with female rats bearing an odor show a learned preference to ejaculate selectively with females that bear the odor. This conditioned ejaculatory preference reflects an association between the odor and the reward state induced by ejaculation. Although little is known about the neuronal mechanisms that mediate this form of learning, convergence of genitosensory and olfactory inputs occurs in both hypothalamic and cortical regions, notably within primary olfactory (piriform) cortex, which may be involved in the encoding or storage of the association. The present study contrasted the ability of genital investigations, mounts, intromissions, ejaculations, and a sexually conditioned olfactory stimulus, to enhance evoked synaptic field potentials in the piriform cortex. Rats in the Paired group underwent conditioning trials in which they copulated with sexually receptive females bearing an almond odor. Rats in the Unpaired control group copulated with receptive females bearing no odor. Responses in the piriform cortex evoked by electrical stimulation of the olfactory bulb were recorded in male rats as they engaged in different aspects of sexual behavior, and were also recorded after conditioning, during exposure to cotton swabs bearing the almond odor. The monosynaptic component of responses was increased during intromission and ejaculation, and the late component of responses was increased during anogenital sniffing and mounting (with or without intromission). However, no differences in the amplitudes of evoked responses were found between the Paired and Unpaired groups, and no differences in synaptic responses were found during presentation of the odor after conditioning. These data indicate that short-term alterations in synaptic responsiveness occur in piriform cortex as a function of sexual stimulation in the male rat, but that responses are not significantly altered by a conditioned odor.

  11. Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

    PubMed

    Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

    2013-09-01

    Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus.

  12. Identified circuit in rat postrhinal cortex encodes essential information for performing specific visual shape discriminations.

    PubMed

    Zhang, Guo-rong; Cao, Haiyan; Kong, Lingxin; O'Brien, Jennifer; Baughns, Andrew; Jan, Mary; Zhao, Hua; Wang, Xiaodan; Lu, Xiu-gui; Cook, Robert G; Geller, Alfred I

    2010-08-10

    Learning theories hypothesize specific circuits encode essential information for performance. For simple tasks in invertebrates and mammals, the essential circuits are known, but for cognitive functions, the essential circuits remain unidentified. Here, we show that some essential information for performing a choice task is encoded in a specific circuit in a neocortical area. Rat postrhinal (POR) cortex is required for visual shape discriminations, protein kinase C (PKC) pathways mediate changes in neuronal physiology that support learning, and specific PKC genes are required for multiple learning tasks. We used direct gene transfer of a constitutively active PKC to prime a specific POR cortex circuit for learning visual shape discriminations. In the experiment, rats learned a discrimination, received gene transfer, learned new discriminations, received a small lesion that ablated approximately 21% of POR cortex surrounding the gene transfer site, and were tested for performance for discriminations learned either before or after gene transfer. Lesions of the genetically targeted circuit selectively interfered with performance for discriminations learned after gene transfer. Activity-dependent gene imaging confirmed increased activity in the genetically targeted circuit during learning and showed the essential information was sparse-coded in approximately 500 neurons in the lesioned area. Wild-type rats contained circuits with similar increases in activity during learning, but these circuits were located at unpredictable, different positions in POR cortex. These results establish that some essential information for performing specific visual discriminations can be encoded in a small, identified, neocortical circuit and provide a foundation for characterizing the circuit and essential information.

  13. Contralateral somatosensory neglect in unrestrained rats after lesion of the parietal cortex of the left hemisphere.

    PubMed

    Holm, S; Mogensen, J

    1993-01-01

    Three groups of rats were studied: a sham operated control group and two groups in which the parietal "association" cortex had been ablated in the left and right hemispheres respectively. Twenty-four hours and 8 days postoperatively the animals were subjected to a test in which their responsiveness to lateralized somatosensory stimuli was measured while the rats were left unrestrained. Additionally, an activity cage locomotion test followed immediately upon both tests of somatosensory responsiveness. Twenty-four hours postoperatively the animals in which the parietal cortex of the left hemisphere had been ablated demonstrated a significant contralateral neglect of somatosensory stimuli while the group in which the right parietal cortex had been ablated only exhibited a non-significant tendency to a contralateral neglect. While the activity cage test did not reveal an overall difference in the activity level of the three groups the latency to initiate locomotion in the activity cage was found to be significantly decreased in both ablated groups. Eight days postoperatively both ablated groups appeared fully recovered. It is concluded that ablations of the parietal "association" cortex of the rat are associated with a syndrome of contralateral somatosensory neglect that can even be demonstrated if the animals are left unrestrained during testing.

  14. Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex

    PubMed Central

    Majumdar, Anuradha S.; Nirwane, Abhijit; Kamble, Rahul

    2014-01-01

    Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3. PMID:25253934

  15. Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex

    PubMed Central

    Soltani, Narjes; Mohammadi, Elham; Allahtavakoli, Mohammad; Shamsizadeh, Ali; Roohbakhsh, Ali; Haghparast, Abbas

    2016-01-01

    Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID:27563414

  16. From visual affordances in monkey parietal cortex to hippocampo-parietal interactions underlying rat navigation.

    PubMed Central

    Arbib, M A

    1997-01-01

    This paper explores the hypothesis that various subregions (but by no means all) of the posterior parietal cortex are specialized to process visual information to extract a variety of affordances for behaviour. Two biologically based models of regions of the posterior parietal cortex of the monkey are introduced. The model of the lateral intraparietal area (LIP) emphasizes its roles in dynamic remapping of the representation of targets during a double saccade task, and in combining stored, updated input with current visual input. The model of the anterior intraparietal area (AIP) addresses parietal-premotor interactions involved in grasping, and analyses the interaction between the AIP and premotor area F5. The model represents the role of other intraparietal areas working in concert with the inferotemporal cortex as well as with corollary discharge from F5 to provide and augment the affordance information in the AIP, and suggests how various constraints may resolve the action opportunities provided by multiple affordances. Finally, a systems-level model of hippocampo parietal interactions underlying rat navigation is developed, motivated by the monkey data used in developing the above two models as well as by data on neurones in the posterior parietal cortex of the monkey that are sensitive to visual motion. The formal similarity between dynamic remapping (primate saccades) and path integration (rat navigation) is noted, and certain available data on rat posterior parietal cortex in terms of affordances for locomotion are explained. The utility of further modelling, linking the World Graph model of cognitive maps for motivated behaviour with hippocampal-parietal interactions involved in navigation, is also suggested. These models demonstrate that posterior parietal cortex is not only itself a network of interacting subsystems, but functions through cooperative computation with many other brain regions. PMID:9368931

  17. Regional variability in age-related loss of neurons from the primary visual cortex and medial prefrontal cortex of male and female rats

    PubMed Central

    Yates, M.A.; Markham, J.A.; Anderson, S.E.; Morris, J.R.; Juraska, J.M.

    2008-01-01

    During aging, changes in the structure of the cerebral cortex of the rat have been seen, but potential changes in neuron number remain largely unexplored. In the present study, stereological methods were used to examine neuron number in the medial prefrontal cortex and primary visual cortex of young adult (85–90 days of age) and aged (19–22 months old) male and female rats in order to investigate any age-related losses. Possible sex differences in aging were also examined since sexually dimorphic patterns of aging have been seen in other measures. An age-related loss of neurons (18–20%), which was mirrored in volume losses, was found to occur in the primary visual cortex in both sexes in all layers except IV. Males, but not females, also lost neurons (15 %) from layer V/VI of the ventral medial prefrontal cortex and showed an overall decrease in volume of this region. In contrast, dorsal medial prefrontal cortex showed no age-related changes. The effects of aging clearly differ among regions of the rat brain and to some degree, between the sexes. PMID:18513705

  18. Electrophysiological and morphological properties of neurons in layer 5 of the rat postrhinal cortex.

    PubMed

    Sills, Joseph B; Connors, Barry W; Burwell, Rebecca D

    2012-09-01

    The postrhinal (POR) cortex of the rat is homologous to the parahippocampal cortex of the primate based on connections and other criteria. POR provides the major visual and visuospatial input to the hippocampal formation, both directly to CA1 and indirectly through connections with the medial entorhinal cortex. Although the cortical and hippocampal connections of the POR cortex are well described, the physiology of POR neurons has not been studied. Here, we examined the electrical and morphological characteristics of layer 5 neurons from POR cortex of 14- to 16-day-old rats using an in vitro slice preparation. Neurons were subjectively classified as regular-spiking (RS), fast-spiking (FS), or low-threshold spiking (LTS) based on their electrophysiological properties and similarities with neurons in other regions of neocortex. Cells stained with biocytin included pyramidal cells and interneurons with bitufted or multipolar dendritic patterns. Similarity analysis using only physiological data yielded three clusters that corresponded to FS, LTS, and RS classes. The cluster corresponding to the FS class was composed entirely of multipolar nonpyramidal cells, and the cluster corresponding to the RS class was composed entirely of pyramidal cells. The third cluster, corresponding to the LTS class, was heterogeneous and included both multipolar and bitufted dendritic arbors as well as one pyramidal cell. We did not observe any intrinsically bursting pyramidal cells, which is similar to entorhinal cortex but unlike perirhinal cortex. We conclude that POR includes at least two major classes of neocortical inhibitory interneurons, but has a functionally restricted cohort of pyramidal cells.

  19. Effects of naltrexone on firing activity of rat cortex neurons and its interactions with ethanol.

    PubMed

    Kozhechkin, S N; Mednikova, Yu S; Kolik, L G

    2013-09-01

    Naltrexone dose-dependently decreased neuron firing rate in the rat frontal cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration. Microelectrophoretic applications of naltrexone reduced the excitatory neuronal response of neurons to low doses of ethanol (electroosmotic application) and potentiated depression of firing activity induced by ethanol in high doses. We concluded that opioid peptides take part in generation of spontaneous neuronal activity in the frontal cortex and neuronal excitation caused by ethanol in low doses. Naltrexone acts as a synergist of ethanol in its depressive effect on cortical neurons.

  20. Neuroanatomical study on the tecto-suprageniculate-dorsal auditory cortex pathway in the rat.

    PubMed

    Horie, M; Meguro, R; Hoshino, K; Ishida, N; Norita, M

    2013-01-03

    Previous anatomical and physiological studies suggest that the superior colliculus sends integrated sensory information to the multimodal cortical areas via the thalamic suprageniculate nucleus (SG). However, the detailed distribution of rat tecto-SG axon terminals and SG neurons projecting to the multimodal cortex, as well as synaptic connections between these tectal axons and SG neurons, remains unclear. In this study, the organization of the tecto-thalamo-cortical pathway was investigated via combined injections of anterograde and retrograde tracers followed by light and electron microscopic observations. Injections of a retrograde tracer, cholera toxin B subunit (CTB), into the temporal cortex, area 2, dorsal part (Te2D), and injections of an anterograde tracer, biotinylated dextran amine (BDA), into the deep layers of the superior colliculus produced the following results: (1) Retrogradely CTB-labeled neurons were found throughout SG, predominantly in its rostral part. CTB-labeled neurons were also found in other cortical areas such as the visual cortex, the auditory cortex, the parietal association cortex, and the perirhinal cortex. (2) Anterogradely BDA-labeled axons and their terminals were also observed throughout SG. Dual visualization of BDA and CTB showed that retrogradely labeled SG neurons and anterogradely labeled tectal axon terminal boutons overlapped considerably in the rostral part of SG, and their direct synaptic contacts were also confirmed via electron microscopy. These findings suggest that multimodal information from the superior colliculus can be processed directly in SG neurons projecting to Te2D.

  1. Involvement of glutamate and gamma-aminobutyric acid (GABA)-ergic systems in thyrotropin-releasing hormone-induced rat cerebellar cGMP formation.

    PubMed

    Nakayama, T; Hashimoto, T; Nagai, Y

    1996-12-05

    The increase in cyclic guanosine 3',5'-monophosphate (cGMP) caused by subcutaneous injection of thyrotropin-releasing hormone (TRH) tartrate was observed in a region-specific manner in the rat cerebellum. TRH tartrate (TRH-T) (2.8, 7.0 and 17 mg/kg as free TRH, s.c.) produced dose-dependent increases in cGMP levels markedly in the cerebellar superior and inferior vermis, and a smaller but still significant increase in the cerebellar hemispheres and brainstem but no significant increases in other brain regions. The TRH-induced increase in the cGMP level in the cerebellum was suppressed by pretreatment with muscimol, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one) or MK-801 (dizocilpine maleate) and partially suppressed by atropine but was not suppressed by chlordiazepoxide, oxazepam, phentolamine, propranolol, cyproheptadine, haloperidol, baclofen or DNQX (6,7-dinitroquinoxaline-2,3-dione), suggesting the possible involvement of GABA (gamma-aminobutyric acid)(A)-ergic, N-methyl-D-aspartate (NMDA)-type glutamatergic and cholinergic systems. These results suggest that excitatory amino acids may be involved in the cGMP formation caused by TRH in the cerebellar areas, and that cGMP formation is inhibited by enhancement of GABAA receptor function.

  2. GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons

    PubMed Central

    Lu, Jun-Mei; Wang, Chang-Ying; Hu, Changlong; Fang, Yan-Jia; Mei, Yan-Ai

    2016-01-01

    GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K+ currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca2+ concentration ([Ca2+]i) in response to membrane depolarization, as determined by Ca2+ imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca2+ current (ICa) without altering steady-state activation of Ca2+ channels. Treatment with nifedipine, an inhibitor of L-type Ca2+ channels, abrogated GDF-15-induced increases in [Ca2+]i and ICa. The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TβRII phosphorylation. Given that Cav1.3 is not only a channel for Ca2+ influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TβRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons. PMID:27114559

  3. Low-threshold Ca2+ currents in dendritic recordings from Purkinje cells in rat cerebellar slice cultures.

    PubMed

    Mouginot, D; Bossu, J L; Gähwiler, B H

    1997-01-01

    Voltage-dependent Ca2+ conductances were investigated in Purkinje cells in rat cerebellar slice cultures using the whole-cell and cell-attached configurations of the patch-clamp technique. In the presence of 0.5 mM Ca2+ in the extracellular solution, the inward current activated with a threshold of -55 +/- 1.5 mV and reached a maximal amplitude of 2.3 +/- 0.4 nA at -31 +/- 2 mV. Decay kinetics revealed three distinct components: a fast (24.6 +/- 2 msec time constant), a slow (304 +/- 46 msec time constant), and a nondecaying component. Rundown of the slow and sustained components of the current, or application of antagonists for the P/Q-type Ca2+ channels, allowed isolation of the fast-inactivating Ca2+ current, which had a threshold for activation of -60 mV and reached a maximal amplitude of 0.7 nA at a membrane potential of -33 mV. Both activation and steady-state inactivation of this fast-inactivating Ca2+ current were described with Boltzmann equations, with half-activation and inactivation at -51 mV and -86 mV, respectively. This Ca2+ current was nifedipine-insensitive, but its amplitude was reduced reversibly by bath-application of NiCl2 and amiloride, thus allowing its identification as a T-type Ca2+ current. Channels with a conductance of 7 pS giving rise to a fast T-type ensemble current (insensitive to omega-Aga-IVA) were localized with a high density on the dendritic membrane. Channel activity responsible for the ensemble current sensitive to omega-Aga-IVA was detected with 10 mM Ba2+ as the charge carrier. These channels were distributed with a high density on dendritic membranes and in rare cases were also seen in somatic membrane patches.

  4. Cerebellar Insulin/IGF-1 signaling in diabetic rats: Effects of exercise training.

    PubMed

    Borges, Mariana Eiras; Ribeiro, Alessandra Mussi; Pauli, José Rodrigo; Arantes, Luciana Mendonça; Luciano, Eliete; de Moura, Leandro Pereira; de Almeida Leme, José Alexandre Curiacos; Medeiros, Alessandra; Bertolini, Natália Oliveira; Sibuya, Clarice Yoshiko; Gomes, Ricardo José

    2017-02-03

    The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32mg/kgb.w.). The training program consisted in swimming 5days/week, 1h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3β, IRβ and IGF-1R and the phosphorylation of β-amyloid, Tau, ERK1+ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups; however, in TD, there was a reduction in hyperglycemia compared to SD. Diabetes increased Tau and β-amyloid phosphorylation in both SD and TD groups. Furthermore, aerobic exercise increased ERK1+ERK2 expression in TC. The data showed that in cerebellum of diabetic rats induced by alloxan there are some proteins expression like Parkinson cerebellum increased, and the exercise training was not able to modulate the expression of these proteins.

  5. Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract.

    PubMed

    Krishnakumar, Amee; Abraham, Pretty Mary; Paul, Jes; Paulose, C S

    2009-09-15

    Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.

  6. Decreased norepinephrine (NE) uptake in cerebral cortex and inferior colliculus of genetically epilepsy prone (GEP) rats

    SciTech Connect

    Browning, R.A.; Rigler-Daugherty, S.K.; Long, G.; Jobe, P.C.; Wade, D.R.

    1986-03-01

    GEP rats are characterized by an enhanced susceptibility to seizures caused by a variety of stimuli, most notably sound. Pharmacological treatments that reduce the synaptic concentration of NE increase seizure severity in GEP rats while elevations in NE have the opposite effect. GEP rats also display a widespread deficit in brain NE concentration suggesting that their increased seizure susceptibility is related to a deficit in noradrenergic transmission. The authors have compared the kinetics of /sup 3/H-NE uptake in the P/sub 2/ synaptosomal fraction isolated from the cerebral cortex of normal and GEP-rats. Although the apparent Kms were not significantly different (Normal +/- SEM:0.37 +/- 0.13..mu..M; GEP +/- SEM: 0.29 +/- 0.07..mu..M), the Vmax for GEP rats was 48% lower than that of normal rats (Normal +/- SEM: 474 +/- 45 fmole/mg/4min; GEP +/- SEM: 248 +/- 16 fmole/mg/4min). Because of the possible role of the inferior colliculus (IC) in the initiation of sound-induced seizures in GEP rats, the authors measured synaptosomal NE uptake in the IC using a NE concentration of 50 nM. The IC synaptosomal NE uptake was found to be 35% lower in GEP than in normal rats. These findings are consistent with the hypothesis that a deficit in noradrenergic transmission is related to the increased seizure susceptibility of GEP rats.

  7. Enhanced Behavioral Recovery from Sensorimotor Cortex Lesions After Pyramidotomy in Adult Rats

    PubMed Central

    Fanardjian, V. V.; Gevorkyan, O. V.; Mallina, R. K.; Melik-Moussian, A. B.; Meliksetyan, I. B.

    2000-01-01

    Unilateral transection of the bulbar pyramid, performed before the ablation of the ipsilateral sensorimotor cortex, has been shown to facilitate the recovery of operantly conditioned reflexes and compensatory processes in rats. Such enhanced behaviorai recovery was absent when only the sensorimotor cortex was ablated. This phenomenon is explained by the switching of motor activity under the control of the cortico-rubrospinal system. Switching of the descending influences is accomplished through the following loop: cortico-rubrai projectionred nucleus-inferior olive-cerebellum-thalamuscerebral cortex. This suggests that a preliminary lesion of the peripheral part of the system, represented by a descending spinal projection, facilitates the recovery processes to develop during the subsequent destruction of its central part. PMID:11486486

  8. Beta 2-adrenergic receptors are colocalized and coregulated with whisker barrels in rat somatosensory cortex

    SciTech Connect

    Vos, P.; Kaufmann, D.; Hand, P.J.; Wolfe, B.B. )

    1990-07-01

    Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-adrenergic receptors, but not beta 1-adrenergic receptors colocalize with whisker barrels in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array.

  9. A radial map of multi-whisker correlation selectivity in the rat barrel cortex

    PubMed Central

    Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E.; Bourdieu, Laurent; Léger, Jean- François

    2016-01-01

    In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel–septal borders, forming rings of multi-whisker synchrony-preferring cells. PMID:27869114

  10. Decrease in doublecortin expression without neuronal cell death in rat retrosplenial cortex after stress exposure.

    PubMed

    Kutsuna, Nobuo; Suma, Takeshi; Takada, Yoshiyuki; Yamashita, Akiko; Oshima, Hideki; Sakatani, Kaoru; Yamamoto, Takamitsu; Katayama, Yoichi

    2012-03-07

    Exposure to acute stress by forced swim impairs spatial learning and memory in rats. The retrosplenial cortex plays an important role in spatial learning and memory. A cell population that expresses immature neuronal markers, including doublecortin (DCX), plays a key role in plasticity of the adult brain through formation of new neurons. Here, we aimed to determine whether rats exposed to acute stress showed changes in DCX expression in retrosplenial cortex cells. Twelve male Sprague-Dawley rats were used. Six were subjected to acute stress by forced swim (group S), and the remaining six served as controls (group C). Immunohistochemical staining was performed for DCX, neuron-specific nuclear protein, parvalbumin, calbindin, calretinin, and somatostatin. Newly generated cells were immunohistochemically detected by daily administration of 5-bromo-2'-deoxyuridine for 1 week. Fluoro-Jade B staining was performed to detect cell death. Group S showed lower number of DCX-expressing cells than group C (P<0.001). The proportion of DCX-expressing cells showing neuron-specific nuclear protein co-localization (24% in group S; 27% in group C) or parvalbumin co-localization (65% in group S; 61% in group C) remained unchanged after acute stress exposure. Neither 5-bromo-2'-deoxyuridine-positive nor Fluoro-Jade B-positive cells were found in the retrosplenial cortex of groups S and C. DCX-expressing cells in the retrosplenial cortex decreases markedly without cell death after acute stress exposure. Neuronal differentiation of these cells toward gamma aminobutyric acidergic interneurons appears to be unaltered. The decrease in DCX expression may reduce plasticity potential within the retrosplenial cortex and attenuate spatial learning and memory function.

  11. Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

    PubMed

    Wisor, J P; Morairty, S R; Huynh, N T; Steininger, T L; Kilduff, T S

    2006-08-11

    Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

  12. Cerebellar Ataxia.

    PubMed

    Perlman

    2000-05-01

    There is nothing more discouraging than for a patient to be given a specific diagnosis, then to be told that there is nothing that can be done. Physicians are equally disheartened to see exponential progress being made in the understanding of the pathophysiology of a complex disorder but few direct benefits resulting for their patients. Over the past 5 years, molecular genetic research has completely revolutionized the way in which the progressive cerebellar ataxias are classified and diagnosed, but it has yet to produce effective gene-based, neuroprotective, or neurorestorative therapies. The treatment of cerebellar ataxia remains primarily a neurorehabilitation challenge, employing physical, occupational, speech, and swallowing therapy; adaptive equipment; driver safety training; and nutritional counseling. Modest additional gains are seen with the use of medications that can improve imbalance, incoordination, or dysarthria (amantadine, buspirone, acetazolamide); cerebellar tremor (clonazepam, propranolol); and cerebellar or central vestibular nystagmus (gabapentin, baclofen, clonazepam). Many of the progressive cerebellar syndromes have associated features involving other neurologic systems (eg, spasticity, dystonia or rigidity, resting or rubral tremor, chorea, motor unit weakness or fatigue, autonomic dysfunction, peripheral or posterior column sensory loss, neuropathic pain or cramping, double vision, vision and hearing loss, dementia, and bowel, bladder, and sexual dysfunction), which can impede the treatment of the ataxic symptoms or can worsen with the use of certain drugs. Treatment of the associated features themselves may in turn worsen the ataxia either directly (as side effects of medication) or indirectly (eg, relaxation of lower limb spasticity that was acting as a stabilizer for an ataxic gait). Secondary complications of progressive ataxia can include deconditioning or immobility, weight loss or gain, skin breakdown, recurrent pulmonary and

  13. Cerebellar Stroke-manifesting as Mania

    PubMed Central

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R.; Muralidharan, Rengarajalu

    2014-01-01

    Secondary mania resulting from cerebral Cortex are described commonly. But secondary mania produced by cerebellar lesions are relatively uncommon. This case report describes a patient who developed cerebellar stoke and manic features simultaneously. 28 years old male developed giddiness and projectile vomiting. Then he would lie down for about an hour only to find that he could not walk. He became quarrelsome. His Psycho motor activities and speech were increased. He was euphoric and was expressing grandiose ideas. Bender Gestalt Test showed signs of organicity. Score in Young mania relating scale was 32; productivity was low in Rorschach. Neurological examination revealed left cerebellar signs like ataxia and slurring of speech. Computed tomography of brain showed left cerebellar infarct. Relationship between Psychiatric manifestations and cerebellar lesion are discussed. PMID:25035567

  14. Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

    PubMed

    Wabno, Joanna; Hess, Grzegorz

    2013-05-01

    Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach. In slices prepared 2 days after the last drug administration from animals receiving imipramine for 14 days (dose 10 mg/kg p.o., twice daily) the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from layer II/III pyramidal neurons was decreased, while the mean amplitude of sIPSCs was increased. These effects were absent in slices obtained from rats which received imipramine once. Application of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN 082), a selective mGluR7 allosteric agonist, to the slice incubation medium resulted in a decrease in the mean frequency of sIPSCs in preparations obtained from repeated imipramine-treated animals, in contrast to slices originating from control rats where no AMN 082-induced effects were observed. Repeated imipramine treatment reduced protein density levels of the three tested GABAA receptor subunits: α 1, β 2 and γ 2. These data indicate that repeated treatment of normal rats with imipramine results in a modification of the release mechanism of GABA from presynaptic terminals and its modulation by mGluR7 receptors as well as in an alteration in GABAA receptor subunit protein levels in the rat cerebral cortex.

  15. Emergence of transformation-tolerant representations of visual objects in rat lateral extrastriate cortex.

    PubMed

    Tafazoli, Sina; Safaai, Houman; De Franceschi, Gioia; Rosselli, Federica Bianca; Vanzella, Walter; Riggi, Margherita; Buffolo, Federica; Panzeri, Stefano; Zoccolan, Davide

    2017-04-11

    Rodents are emerging as increasingly popular models of visual functions. Yet, evidence that rodent visual cortex is capable of advanced visual processing, such as object recognition, is limited. Here we investigate how neurons located along the progression of extrastriate areas that, in the rat brain, run laterally to primary visual cortex, encode object information. We found a progressive functional specialization of neural responses along these areas, with: (1) a sharp reduction of the amount of low-level, energy-related visual information encoded by neuronal firing; and (2) a substantial increase in the ability of both single neurons and neuronal populations to support discrimination of visual objects under identity-preserving transformations (e.g., position and size changes). These findings strongly argue for the existence of a rat object-processing pathway, and point to the rodents as promising models to dissect the neuronal circuitry underlying transformation-tolerant recognition of visual objects.

  16. Lesions of the Orbitofrontal but Not Medial Prefrontal Cortex Affect Cognitive Judgment Bias in Rats

    PubMed Central

    Golebiowska, Joanna; Rygula, Rafal

    2017-01-01

    Neuroimaging studies in humans have recently shown that the prefrontal cortex (PFC) and orbitofrontal cortex (OFC) mediate bias in the judgment of forthcoming events. In the present study, we sought to determine whether cognitive judgment bias (CJB) is also dependent on these prefrontal regions in non-human animals. For this, we trained a cohort of rats in the ambiguous-cue interpretation (ACI) paradigm, subjected them to excitotoxic lesions in the medial PFC (mPFC) and OFC, and tested the effects of neuronal loss within these regions on CJB. Comparison of the lesions’ behavioral effects in the ACI paradigm revealed that neuronal loss within the OFC but not within the mPFC influences the interpretation of ambiguous cues by animals. Our findings demonstrate the specific involvement of the OFC in CJB in rats. PMID:28377703

  17. Adaptive categorization of sound frequency does not require the auditory cortex in rats.

    PubMed

    Gimenez, Tyler L; Lorenc, Maja; Jaramillo, Santiago

    2015-08-01

    A defining feature of adaptive behavior is our ability to change the way we interpret sensory stimuli depending on context. Rapid adaptation in behavior has been attributed to frontal cortical circuits, but it is not clear if sensory cortexes also play an essential role in such tasks. In this study we tested whether the auditory cortex was necessary for rapid adaptation in the interpretation of sounds. We used a two-alternative choice sound-categorization task for rats in which the boundary that separated two acoustic categories changed several times within a behavioral session. These shifts in the boundary resulted in changes in the rewarded action for a subset of stimuli. We found that extensive lesions of the auditory cortex did not impair the ability of rats to switch between categorization contingencies and sound discrimination performance was minimally impaired. Similar results were obtained after reversible inactivation of the auditory cortex with muscimol. In contrast, lesions of the auditory thalamus largely impaired discrimination performance and, as a result, the ability to modify behavior across contingencies. Thalamic lesions did not impair performance of a visual discrimination task, indicating that the effects were specific to audition and not to motor preparation or execution. These results suggest that subcortical outputs of the auditory thalamus can mediate rapid adaptation in the interpretation of sounds.

  18. Impaired executive function following ischemic stroke in the rat medial prefrontal cortex.

    PubMed

    Cordova, Chris A; Jackson, Danielle; Langdon, Kristopher D; Hewlett, Krista A; Corbett, Dale

    2014-01-01

    Small (lacunar) infarcts frequently arise in frontal and midline thalamic regions in the absence of major stroke. Damage to these areas often leads to impairment of executive function likely as a result of interrupting connections of the prefrontal cortex. Thus, patients experience frontal-like symptoms such as impaired ability to shift ongoing behavior and attention. In contrast, executive dysfunction has not been demonstrated in rodent models of stroke, thereby limiting the development of potential therapies for human executive dysfunction. Male Sprague-Dawley rats (n=40) underwent either sham surgery or bilateral endothelin-1 injections in the mediodorsal nucleus of the thalamus or in the medial prefrontal cortex. Executive function was assessed using a rodent attention set shifting test that requires animals to shift attention to stimuli in different stimulus dimensions. Medial prefrontal cortex ischemia impaired attention shift performance between different stimulus dimensions while sparing stimulus discrimination and attention shifts within a stimulus dimension, indicating a selective attention set-shift deficit. Rats with mediodorsal thalamic lacunar damage did not exhibit a cognitive impairment relative to sham controls. The selective attention set shift impairment observed in this study is consistent with clinical data demonstrating selective executive disorders following stroke within specific sub-regions of frontal cortex. These data contribute to the development and validation of a preclinical animal model of executive dysfunction, that can be employed to identify potential therapies for ameliorating cognitive deficits following stroke.

  19. Schizophrenia-like GABAergic gene expression deficits in cerebellar Golgi cells from rats chronically exposed to low-dose phencyclidine.

    PubMed

    Bullock, W Michael; Bolognani, Federico; Botta, Paolo; Valenzuela, C Fernando; Perrone-Bizzozero, Nora I

    2009-12-01

    One of the most consistent findings in schizophrenia is the decreased expression of the GABA synthesizing enzymes GAD(67) and GAD(65) in specific interneuron populations. This dysfunction is observed in distributed brain regions including the prefrontal cortex, hippocampus, and cerebellum. In an effort to understand the mechanisms for this GABA deficit, we investigated the effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist phencyclidine (PCP), which elicits schizophrenia-like symptoms in both humans and animal models, in a chronic, low-dose exposure paradigm. Adult rats were given PCP at a dose of 2.58 mg/kg/day i.p. for a month, after which levels of various GABAergic cell mRNAs and other neuromodulators were examined in the cerebellum by qRT-PCR. Administration of PCP decreased the expression of GAD(67), GAD(65), and the presynaptic GABA transporter GAT-1, and increased GABA(A) receptor subunits similar to those seen in patients with schizophrenia. Additionally, we found that the mRNA levels of two Golgi cell selective NMDAR subunits, NR2B and NR2D, were decreased in PCP-treated rats. Furthermore, we localized the deficits in GAD(67) expression solely to these interneurons. Slice electrophysiological studies showed that spontaneous firing of Golgi cells was reduced by acute exposure to low-dose PCP, suggesting that these neurons are particularly vulnerable to NMDA receptor antagonism. In conclusion, our results demonstrate that chronic exposure to low levels of PCP in rats mimics the GABAergic alterations reported in the cerebellum of patients with schizophrenia (Bullock et al., 2008. Am. J. Psychiatry 165, 1594-1603), further supporting the validity of this animal model.

  20. Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats

    PubMed Central

    CHIN, SO YEON; PANDEY, KAILASH N.; SHI, SHANG-JIN; KOBORI, HIROYUKI; MORENO, CAROL; NAVAR, L. GABRIEL

    2008-01-01

    We have previously demonstrated that nitric oxide (NO) exerts a greater modulatory influence on renal cortical blood flow in ANG II-infused hypertensive rats compared with normotensive rats. In the present study, we determined nitric oxide synthase (NOS) activities and protein levels in the renal cortex and medulla of normotensive and ANG II-infused hypertensive rats. Enzyme activity was determined by measuring the rate of formation of l-[14C]citrulline from l-[14C]arginine. Western blot analysis was performed to determine the regional expression of endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) isoforms in the renal cortex and medulla of control and ANG II-infused rats. Male Sprague-Dawley rats were prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days and compared with sham-operated rats. Systolic arterial pressures were 127 ± 2 and 182 ± 3 mmHg in control (n = 13) and ANG II-infused rats (n = 13), respectively. The Ca2+-dependent NOS activity, expressed as picomoles of citrulline formed per minute per gram wet weight, was higher in the renal cortex of ANG II-infused rats (91 ± 11) than in control rats (42 ± 12). Likewise, both eNOS and nNOS were markedly elevated in the renal cortex of the ANG II-treated rats. In both groups of rats, Ca2+-dependent NOS activity was higher in the renal medulla than in the cortex; however, no differences in medullary NOS activity were observed between the groups. Also, no differences in medullary eNOS levels were observed between the groups; however, medullary nNOS was decreased by 45% in the ANG II-infused rats. For the Ca2+-independent NOS activities, the renal cortex exhibited a greater activity in the control rats (174 ± 23) than in ANG II-infused rats (101 ± 10). Similarly, cortical iNOS was greater by 47% in the control rats than in ANG II-treated rats. No differences in the activity were found for the renal medulla between the groups. There was

  1. Taste-potentiated odor aversion learning in rats with lesions of the insular cortex.

    PubMed

    Lin, Jian-You; Roman, Christopher; Reilly, Steve

    2009-11-10

    The current study assessed the influence of excitotoxic lesions of the insular cortex (IC) on taste-potentiated odor aversion (TPOA) learning. Water-deprived rats initially received a single odor-toxicosis or odor/taste-toxicosis pairing and were subsequently tested, in separate trials, with the odor and the taste stimulus. Indicating TPOA, neurologically intact rats conditioned with the odor/taste compound stimulus acquired significantly stronger odor aversions than normal rats conditioned with the odor stimulus. IC lesions disrupted TPOA, conditioned taste aversion and taste neophobia. The finding that taste did not potentiate odor aversion learning in the IC-lesioned rats provides support for the "within-compound association" analysis but is inconsistent with the "sensory-and-gate" account of TPOA learning.

  2. Cross-sectional imaging of functional activation in the rat somatosensory cortex with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Aguirre, A. D.; Chen, Y.; Ruvinskaya, L.; Devor, A.; Boas, D. A.; Fujimoto, J. G.

    2005-08-01

    Simultaneous optical coherence tomography (OCT) and video microscopy were performed on the rat somatosensory cortex through a thinned skull during forepaw stimulation. Fractional change measurements in OCT images reveal a functional signal timecourse similar to well understood hemodynamic signal timecourses measured with video microscopy. The precise etiology of the observed OCT functional signal is still under investigation, but these results suggest that OCT can provide high-resolution cross-sectional images of functional neuro-vascular activation.

  3. Rapid plasticity follows whisker pairing in barrel cortex of the awake rat.

    PubMed

    Sellien, Heike; Ebner, Ford F

    2007-02-01

    Synaptic plasticity can be induced easily throughout life in the rodent somatic sensory cortex. Trimming all but two whiskers on one side of an adult rat's face, called 'whisker pairing', causes the active (intact) whiskers to develop a stronger drive on cortical cells in their respective barrel columns, while inactive (trimmed) whisker efficacy is down-regulated. To date, this type of activity-dependent plasticity has been induced by trimming all but two whiskers, letting the rats explore their environment from 1 day to 1 month, after which cortical responses were analyzed physiologically under anesthesia. Such studies have enhanced our understanding of cortical plasticity, but the anesthesia complicates the examination of changes that occur in the first few hours after whisker trimming. Here we assayed the short-term changes that occur in alert, active animals over a period of hours after whisker trimming. The magnitude of barrel cortex evoked responses was measured in response to stimulation of the cut and paired whiskers of rats under several conditions: (a) whisking in air (control), (b) active whisking of an object by the rat, and (c) epochs of passive whisker stimulation to identify the onset of whisker pairing plasticity changes in cortex. The main difference between whisking in air without contact and passive whisker stimulation is that the former condition induces an increased response to stimulation of inactive cut whiskers, while the latter condition increases the responses to the stimulated whiskers. The results support the conclusion that whisker pairing plasticity in barrel cortex occurs within 4 h after whisker trimming in an awake, alert animal.

  4. EM colocalization of AMPA and NMDA receptor subunits at synapses in rat cerebral cortex.

    PubMed

    Kharazia, V N; Phend, K D; Rustioni, A; Weinberg, R J

    1996-05-24

    Electrophysiology and light microscopy suggest that a single excitatory synapse may use both amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. Using immunogold electron microscopy, we here provide direct evidence for colocalization at individual synapses in sensorimotor cortex of adult rats. Colocalization was most commonly observed on dendritic spines; subunits of the two classes of receptors seemed to be independently distributed within the synaptic active zone.

  5. Chromaffin cell grafts to rat cerebral cortex reverse lesion-induced memory deficits.

    PubMed

    Welner, S A; Koty, Z C; Boksa, P

    1990-09-10

    Adrenal chromaffin cells were isolated from donor adult rats and transplanted to the cerebral cortex of bilaterally nucleus basalis magnocellularis-lesioned rats. Chromaffin cell grafts to lesioned animals completely reversed the spatial memory deficit seen in lesioned alone animals on a T-maze alternation task. Although chromaffin cell grafts have been used previously to reverse motor abnormalities arising from defective nigro-striatal aminergic transmission, the present report is the first evidence that chromaffin cell transplants can reverse deficits in memory function. Grafts also enhanced cortical acetylcholinesterase staining.

  6. The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning.

    PubMed

    Nelson, A J D; Hindley, E L; Pearce, J M; Vann, S D; Aggleton, J P

    2015-01-01

    The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information.

  7. Discrimination of brief speech sounds is impaired in rats with auditory cortex lesions.

    PubMed

    Porter, Benjamin A; Rosenthal, Tara R; Ranasinghe, Kamalini G; Kilgard, Michael P

    2011-05-16

    Auditory cortex (AC) lesions impair complex sound discrimination. However, a recent study demonstrated spared performance on an acoustic startle response test of speech discrimination following AC lesions (Floody et al., 2010). The current study reports the effects of AC lesions on two operant speech discrimination tasks. AC lesions caused a modest and quickly recovered impairment in the ability of rats to discriminate consonant-vowel-consonant speech sounds. This result seems to suggest that AC does not play a role in speech discrimination. However, the speech sounds used in both studies differed in many acoustic dimensions and an adaptive change in discrimination strategy could allow the rats to use an acoustic difference that does not require an intact AC to discriminate. Based on our earlier observation that the first 40 ms of the spatiotemporal activity patterns elicited by speech sounds best correlate with behavioral discriminations of these sounds (Engineer et al., 2008), we predicted that eliminating additional cues by truncating speech sounds to the first 40 ms would render the stimuli indistinguishable to a rat with AC lesions. Although the initial discrimination of truncated sounds took longer to learn, the final performance paralleled rats using full-length consonant-vowel-consonant sounds. After 20 days of testing, half of the rats using speech onsets received bilateral AC lesions. Lesions severely impaired speech onset discrimination for at least one-month post lesion. These results support the hypothesis that auditory cortex is required to accurately discriminate the subtle differences between similar consonant and vowel sounds.

  8. Linking oscillations in cerebellar circuits

    PubMed Central

    Courtemanche, Richard; Robinson, Jennifer C.; Aponte, Daniel I.

    2013-01-01

    In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4–25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts. PMID:23908606

  9. Hippocampus, perirhinal cortex, and complex visual discriminations in rats and humans

    PubMed Central

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with perirhinal lesions were impaired and did not exhibit the normal preference for exploring the odd object. Notably, rats with hippocampal lesions exhibited the same impairment. Thus, the deficit is unlikely to illuminate functions attributed specifically to perirhinal cortex. Both lesion groups were able to acquire visual discriminations involving the same objects used in the oddity task. Patients with hippocampal damage or larger medial temporal lobe lesions were intact in a similar oddity task that allowed participants to explore objects quickly using eye movements. We suggest that humans were able to rely on an intact working memory capacity to perform this task, whereas rats (who moved slowly among the objects) needed to rely on long-term memory. PMID:25593294

  10. Functional zonation of the rat adrenal cortex: the development and maintenance.

    PubMed

    Mitani, Fumiko

    2014-01-01

    The adrenal cortex of mammals consists of three concentric zones, i.e., the zona glomerulosa (zG), the zona fasciculata (zF), and the zona reticularis (zR), which secrete mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. In 1994, we identified immunohistochemically a new zone between zG and zF of the rat adrenal gland. The zone appeared to be devoid of any significant endocrine functions specific to adrenocortical zones, therefore, we designated the zone as "undifferentiated cell zone (zU)". Further, BrdU (5-bromo-2'-deoxyuridine)-incorporating cells (cells in S-phase) were concentrated at the outer region and the inner region of zU, and these cells proliferated and migrated bidirectionally: toward zG centrifugally and toward zF centripetally. We proposed that cells in and around zU are stem/progenitor cells of the rat adrenal cortex, maintaining functional zonation of the adrenal cortex. The view is consistent with observations reported recently that Sonic hedgehog (Shh), an important factor in embryonic development and adult stem cell maintenance, exists in zU of the rat adrenal gland and the Shh-containing cells seem to migrate bidirectionally.

  11. [Histostructural changes of rat cerebral cortex during hemorrhagic stroke modeling].

    PubMed

    Savos'ko, S I; Chaĭkovs'kyĭ, Iu B; Pogoriela, N Kh; Makarenko, O M

    2012-01-01

    Pathological changes during modeling of primary and secondary acute hemorrhagic stroke were studied in rats. We revealed differences in the activity of pharmacological action of medications under condition of acute stroke. The action of medications increased viability of neurons in both hemispheres of rat cerebrum at a right-side primary and secondary hemorrhagic stroke. Following secondary stroke, the amount of degenerative neurons amounted 25.5 +/- 0.8 cells/mm2, following the action ofcerebrolysin this value was 17.6 +/- 1.7 cells/ mm2 and after the action of cortexine and cerebral this value amounted 18.0 +/- 0.9 cells/mm2 and 10.7 +/- 0.4 cells/ mm2, respectively. In control animals the number of degenerative neurons did not exceed 2% and averaged 1.5 +/- 0.1 cells/mm2. Analysis of the morphological and statistical data showed that the most effective remedies under the primary and secondary hemorrhagic insult are cortexine and cerebral. Cerebral was found to be more effective.

  12. Expression of Phospho-MeCP2s in the Developing Rat Brain and Function of Postnatal MeCP2 in Cerebellar Neural Cell Development.

    PubMed

    Liu, Fang; Ni, Jing-Jing; Sun, Feng-Yan

    2017-02-01

    Abnormal expression and dysfunction of methyl-CpG binding protein 2 (MeCP2) cause Rett syndrome (RTT). The diverse phosphorylation modifications modulate MeCP2 function in neural cells. Using western blot and immunohistochemistry, we examined the expression patterns of MeCP2 and three phospho-MeCP2s (pMeCP2s) in the developing rat brain. The expression of MeCP2 and phospho-S80 (pS80) MeCP2 increased while pS421 MeCP2 and pS292 MeCP2 decreased with brain maturation. In contrast to the nuclear localization of MeCP2 and pS80 MeCP2, pS421 MeCP2 and pS292 MeCP2 were mainly expressed in the cytoplasmic compartment. Apart from their distribution in neurons, they were also detected at a low level in astrocytes. Postnatally-initiated MeCP2 deficiency affected cerebellar neural cell development, as determined by the abnormal expression of GFAP, DCX, Tuj1, MAP-2, and calbindin-D28k. Together, these results demonstrate that MeCP2 and diverse pMeCP2s have distinct features of spatio-temporal expression in the rat brain, and that the precise levels of MeCP2 in the postnatal period are vital to cerebellar neural cell development.

  13. Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

    PubMed

    Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

    2013-12-01

    Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

  14. Dopamine in the prefrontal cortex regulates rats behavioral flexibility to changing reward value.

    PubMed

    Winter, Sabrina; Dieckmann, Marco; Schwabe, Kerstin

    2009-03-02

    Prefrontocortical dopamine (DA) plays an essential role in the representation of reward value and is implicated in behavioral flexibility. We here tested the effect of systemic and local blockade of DA D1- and D2-receptors in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) by using an operant paradigm, where rats have to adjust their behavior to changing reward value. Rats were trained in a Skinner box, where different numbers of lever-presses for pellet-rewards were assigned to and switched between two levers. After rats commit to the efficient lever the lever-occupancy reversed and rats had to switch to the now efficient one. Rats were either intraperitoneally injected with the DA D1-receptor antagonist SCH23390 (40 microg/kg), the DA D2-receptor antagonist sulpiride (10mg/kg), or phosphate buffered saline (PBS). Two other groups received bilateral local mPFC- or OFC-infusions of SCH23390, sulpiride (both 3 microg/0.5 microl), or PBS (0.5 microl) through previously implanted cannulae. After initial detection of reverse of lever-occupancy, systemic and local blockade of D1-receptors increased the number of switches back to the previously efficient lever, thus reducing the total number of reverses completed. D2-receptor blockade deteriorated this measure after local mPFC-infusion. Notably, initial detection of reverse of lever-occupancy was not affected. Blockade of DA receptors within the prefrontal cortex do not deteriorate the detection of changes in reward value, whereas maintenance of behavioral adaptation is disturbed. Interestingly, blockade of DA receptors in the mPFC and OFC had similar effects, i.e., these regions apparently act in a cooperative manner.

  15. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus.

    PubMed

    Amara, Salem; Douki, Thierry; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2011-03-01

    The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl(2), 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats.

  16. Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch-clamp recordings

    PubMed Central

    Roth, Arnd; Häusser, Michael

    2001-01-01

    Simultaneous dendritic and somatic patch-clamp recordings were made from Purkinje cells in cerebellar slices from 12- to 21-day-old rats. Voltage responses to current impulses injected via either the dendritic or the somatic pipette were obtained in the presence of the selective Ih blocker ZD 7288 and blockers of spontaneous synaptic input. Neurons were filled with biocytin for subsequent morphological reconstruction. Four neurons were reconstructed and converted into detailed compartmental models. The specific membrane capacitance (Cm), specific membrane resistance (Rm) and intracellular resistivity (Ri) were optimized by direct fitting of the model responses to the electrophysiological data from the same cell. Mean values were: Cm, 0.77 ± 0.17 μF cm−2 (mean ±s.d.; range, 0.64-1.00 μF cm−2), Rm, 122 ± 18 kΩ cm2 (98-141 kΩ cm2) and Ri, 115 ± 20 Ω cm (93-142 Ω cm). The steady-state electrotonic architecture of these cells was compact under the experimental conditions used. However, somatic voltage-clamp recordings of parallel fibre and climbing fibre synaptic currents were substantially filtered and attenuated. The detailed models were compared with a two-compartment model of Purkinje cells. The range of synaptic current kinetics that can be faithfully recorded using somatic voltage clamp is predicted fairly well by the two-compartment model, even though some of its underlying assumptions are violated. A model of Ih was constructed based on voltage-clamp data, and inserted into the passive compartmental models. Somatic EPSP amplitude was substantially attenuated compared to the amplitude of dendritic EPSPs at their site of generation. However, synaptic efficacy of the same quantal synaptic conductance, as measured by the somatic EPSP amplitude, was only weakly dependent on synaptic location on spiny branchlets. The passive electrotonic structure of Purkinje cells is unusual in that the steady-state architecture is very compact, while voltage transients

  17. Synaptic excitation of individual rat cerebellar granule cells in situ: evidence for the role of NMDA receptors.

    PubMed Central

    D'Angelo, E; De Filippi, G; Rossi, P; Taglietti, V

    1995-01-01

    1. Current-clamp recordings were made in whole-cell patch-clamp configuration from ninety-one granule cells in parasagittal cerebellar slices obtained from 21- to 31-day-old rats. Recordings were performed at 30 degrees C. 2. Resting membrane potential was -58 +/- 6 mV (n = 43). The membrane voltage response to step current injection showed inward rectification consistent with increasing input resistance during membrane depolarization. Over -35 +/- 7 mV (n = 14) repetitive firing with little or no adaptation was activated. Spike frequency increased nearly linearly with injected current. 3. Unitary EPSPs obtained by stimulating the mossy fibre bundle had an amplitude of 11.4 +/- 2.1 mV (n = 22, holding potential = -75 mV). Synchronous activation of greater than one to two mossy fibres was needed to elicit action potentials. Antidromic stimulation elicited antidromic spikes and also EPSPs, presumably through a mossy fibre 'axon reflex'. 4. EPSPs were brought about by NMDA and non-NMDA receptor activation, accounting for about 70 and 30%, respectively, of peak amplitude at the holding potential of -70 mV. The EPSP decay conformed to passive membrane discharge after blocking the NMDA receptors. 5. No appreciable correlation was found between the time-to-peak and decay time constant of the EPSPs, consistent with the compact electrotonic structure of these neurons. 6. During membrane depolarization EPSP amplitude increased transiently, due to both a voltage-dependent increase of the NMDA component and inward rectification. In addition, EPSPs slowed down due to a slowdown of the NMDA component. 7. Temporal summation during high-frequency stimulation was sustained by NMDA receptors, whose contribution to depolarization tended to prevail over that of non-NMDA receptors during the trains. A block of the NMDA receptors resulted in reduced depolarization and output spike frequency. 8. This study, as well as extending previous knowledge to the intracellular level in vivo

  18. Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise

    PubMed Central

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Holschneider, Daniel P.

    2015-01-01

    Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson’s disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4 weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [14C]-iodoantipyrine 1 week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. PMID:25747184

  19. Dysgranular retrosplenial cortex lesions in rats disrupt cross-modal object recognition

    PubMed Central

    Hindley, Emma L.; Nelson, Andrew J.D.; Aggleton, John P.; Vann, Seralynne D.

    2014-01-01

    The retrosplenial cortex supports navigation, with one role thought to be the integration of different spatial cue types. This hypothesis was extended by examining the integration of nonspatial cues. Rats with lesions in either the dysgranular subregion of retrosplenial cortex (area 30) or lesions in both the granular and dysgranular subregions (areas 29 and 30) were tested on cross-modal object recognition (Experiment 1). In these tests, rats used different sensory modalities when exploring and subsequently recognizing the same test objects. The objects were first presented either in the dark, i.e., giving tactile and olfactory cues, or in the light behind a clear Perspex barrier, i.e., giving visual cues. Animals were then tested with either constant combinations of sample and test conditions (light to light, dark to dark), or changed “cross-modal” combinations (light to dark, dark to light). In Experiment 2, visual object recognition was tested without Perspex barriers, but using objects that could not be distinguished in the dark. The dysgranular retrosplenial cortex lesions selectively impaired cross-modal recognition when cue conditions switched from dark to light between initial sampling and subsequent object recognition, but no impairment was seen when the cue conditions remained constant, whether dark or light. The combined (areas 29 and 30) lesioned rats also failed the dark to light cross-modal problem but this impairment was less selective. The present findings suggest a role for the dysgranular retrosplenial cortex in mediating the integration of information across multiple cue types, a role that potentially applies to both spatial and nonspatial domains. PMID:24554671

  20. Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

    PubMed

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

    2015-05-01

    Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.

  1. Altered cerebellar feedback projections in Asperger syndrome.

    PubMed

    Catani, Marco; Jones, Derek K; Daly, Eileen; Embiricos, Nitzia; Deeley, Quinton; Pugliese, Luca; Curran, Sarah; Robertson, Dene; Murphy, Declan G M

    2008-07-15

    It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (p<0.001) and right superior cerebellar (output) peduncle (p<0.001) compared to controls; but no difference in the input tracts. Severity of social impairment, as measured by the Autistic Diagnostic Interview, was negatively correlated with diffusion anisotropy in the fibres of the left superior cerebellar peduncle. These findings suggest a vulnerability of specific cerebellar neural pathways in people with Asperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.

  2. Output of Neurogliaform Cells to Various Neuron Types in the Human and Rat Cerebral Cortex

    PubMed Central

    Oláh, Szabolcs; Komlósi, Gergely; Szabadics, János; Varga, Csaba; Tóth, Éva; Barzó, Pál; Tamás, Gábor

    2007-01-01

    Neurogliaform cells in the rat elicit combined GABAA and GABAB receptor-mediated postsynaptic responses on cortical pyramidal cells and establish electrical synapses with various interneuron types. However, the involvement of GABAB receptors in postsynaptic effects of neurogliaform cells on other GABAergic interneurons is not clear. We measured the postsynaptic effects of neurogliaform cells in vitro applying simultaneous whole-cell recordings in human and rat cortex. Single action potentials of human neurogliaform cells evoked unitary IPSPs composed of GABAA and GABAB receptor-mediated components in various types of inteneuron and in pyramidal cells. Slow IPSPs were combined with homologous and heterologous electrical coupling between neurogliaform cells and several human interneuron types. In the rat, single action potentials in neurogliaform cells elicited GABAB receptor-mediated component in responses of neurogliaform, regular spiking, and fast spiking interneurons following the GABAA receptor-mediated component in postsynaptic responses. In conclusion, human and rat neurogliaform cells elicit slow IPSPs and reach GABAA and GABAB receptors on several interneuron types with a connection-specific involvement of GABAB receptors. The electrical synapses recorded between human neurogliaform cells and various interneuron types represent the first electrical synapses recorded in the human cortex. PMID:18946546

  3. Nitrergic neurons during early postnatal development of the prefrontal cortex in the rat: histochemical study.

    PubMed

    Hvizdosova, Natalia; Tomasova, Lenka; Bolekova, Adriana; Kolesar, Dalibor; Kluchova, Darina

    2014-06-01

    The presence of nitrergic cells in the prefrontal cortex has been confirmed, however little is known about the postnatal development of these cells. Nitrergic neurons were studied histochemically by using NADPH-diaphorase staining in the prefrontal cortex of male Wistar rats from postnatal day 7-21 (P7-21). Neuronal NADPH-diaphorase is a nitric oxide synthase that provides a specific histochemical marker for neurons producing nitric oxide (NO). NO acts as a neurotransmitter and intracellular signaling molecule in the nervous system. We observed in 7 day old rats NADPH-d containing neurons that were intensely stained. These neurons were bipolar with a short dendrite with average length of 23 μm. During the second postnatal week, the neurons were mainly bipolar and were rarely multipolar. By P14 the cells were located primarily in cortical layers III-VI. Nitrergic neurons of the 21 day old rats were histochemically identified as multipolar cells with long radial extending dendrites. Dendrites of neurons in 14 and 21 day old rats were a similar length with an average of 57 μm. These results suggest that nitrergic neurons differentiate during a relatively short period of time and reach their structural maturity by the end of the second week of postnatal development.

  4. Quantitative analysis of somatosensory cortex development in metatherians and monotremes, with comparison to the laboratory rat.

    PubMed

    Ashwell, Ken W S

    2015-01-01

    Metatherians and monotremes are born in an immature state, followed by prolonged nurturing by maternal lactation. Quantitative analysis of isocortical sections held in the collections at the Museum für Naturkunde, Berlin was used to compare the pace of somatosensory cortex development relative to body size and pallial thickness between metatherian groups, monotremes, and the laboratory rat. Analysis indicated that the pace of pallial growth in the monotremes is much lower than that in the metatherians or laboratory rat, with an estimated 8.6-fold increase in parietal cortex thickness between 10 and 100 mm body length, compared to a 10- to 20-fold increase among the metatherians and the rat. It was found that aggregation of cortical plate neurons occurs at similar embryo size in the mammals studied (around 8-14 mm body length) and a similar pallial thickness (around 200 µm), but that proliferative zone involution occurs at a much higher body size and pallial thickness in the monotremes compared to the metatherians and the laboratory rat. The observations suggest that cortical development in the monotremes is slower and subject to different regulatory signals to the therians studied. The slow pace may be related to either generally slower metabolism in monotremes or less efficient nutrient supply to the offspring due to the lack of teats.

  5. Involvement of the rostral agranular insular cortex in nicotine self-administration in rats.

    PubMed

    Pushparaj, Abhiram; Kim, Aaron S; Musiol, Martin; Trigo, Jose M; Le Foll, Bernard

    2015-09-01

    Our prior work demonstrated the involvement of the caudal granular subregion of the insular cortex in a rat model of nicotine self-administration. Recent studies in various animal models of addiction for nicotine and other drugs have identified a role for the rostral agranular subregion (RAIC). The current research was undertaken to examine the involvement of the RAIC in a rat model of nicotine self-administration. We investigated the inactivating effects of local infusions of a γ-aminobutyric acid agonist mixture (baclofen/muscimol) into the RAIC on nicotine self-administration under a fixed-ratio 5 (FR-5) schedule and on reinstatement of nicotine seeking induced by nicotine-associated cues in rats. We also evaluated the effects of RAIC inactivation on food self-administration under an FR5 schedule as a control. Inactivation of the RAIC decreased nicotine, but not food, self-administration. RAIC inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues. Our study indicates that the RAIC is involved in nicotine-taking and nicotine-seeking in rats. Modulating insular cortex function appears to be a promising approach for nicotine dependence treatment.

  6. Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

    PubMed Central

    Magistretti, Jacopo; Castelli, Loretta; Forti, Lia; D'Angelo, Egidio

    2006-01-01

    Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage-dependent Na+ currents. In this study we analysed voltage-dependent Na+ currents of rat cerebellar granule cells (GCs) by performing whole-cell, patch-clamp experiments in acute rat cerebellar slices. A transient Na+ current (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at ∼−40 mV, showed half-maximal activation at ∼−55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at −35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR could be accounted for by a 13-state kinetic scheme comprising closed, open, inactivated and blocked states. Current-clamp experiments carried out to identify possible functional correlates of INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP boosts near-threshold firing activity. Our findings suggest that special properties of voltage-dependent Na+ currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially

  7. Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia

    PubMed Central

    2011-01-01

    Background To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects. Methods Purified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods. Results Intra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity. Conclusions These results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab. PMID:21294897

  8. Sound Sequence Discrimination Learning Motivated by Reward Requires Dopaminergic D2 Receptor Activation in the Rat Auditory Cortex

    ERIC Educational Resources Information Center

    Kudoh, Masaharu; Shibuki, Katsuei

    2006-01-01

    We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the…

  9. Role of serotonin transporter function in rat orbitofrontal cortex in impulsive choice.

    PubMed

    Darna, Mahesh; Chow, Jonathan J; Yates, Justin R; Charnigo, Richard J; Beckmann, Joshua S; Bardo, Michael T; Dwoskin, Linda P

    2015-10-15

    Impulsivity is a multi-faceted personality construct that plays a prominent role in drug abuse vulnerability. Dysregulation of 5-hydroxytryptamine (serotonin, 5-HT) systems in subregions of the prefrontal cortex has been implicated in impulsivity. Extracellular 5-HT concentrations are regulated by 5-HT transporters (SERTs), indicating that these transporters may be important molecular targets underlying individual differences in impulsivity and drug abuse vulnerability. The present study evaluated the role of SERT in mediating individual differences in impulsivity. Rats were tested for both impulsive action using the cued go/no-go task and for impulsive choice using a delay discounting task in a counterbalanced design. Following behavioral evaluation, Km and Vmax were obtained from kinetic analysis of [(3)H]5-HT uptake by SERT using synaptosomes prepared from both orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) obtained from each individual rat. Vmax for SERT in OFC, but not mPFC, was negatively correlated with mean adjusted delay scores in the delay discounting task. In contrast, Vmax for SERT in OFC and mPFC was not correlated with performance in the cued go/no-go task. To further evaluate the relationship between SERT function and impulsive choice, a selective SERT inhibitor, fluoxetine (0, 15, 50 and 150pmol/side) was microinjected bilaterally into OFC and effects on the delay discounting task determined. Following stabilization of behavior, fluoxetine increased mean adjusted delay scores (decreased impulsivity) in high impulsive rats compared to saline microinjection, but had no effect in low impulsive rats. These ex vivo and in vivo results suggest that enhanced SERT function in OFC underlies high impulsive choice behavior.

  10. Separate but interacting recognition memory systems for different senses: The role of the rat perirhinal cortex

    PubMed Central

    Albasser, Mathieu M.; Amin, Eman; Iordanova, Mihaela D.; Brown, Malcolm W.; Pearce, John M.; Aggleton, John P.

    2011-01-01

    Two different models (convergent and parallel) potentially describe how recognition memory, the ability to detect the re-occurrence of a stimulus, is organized across different senses. To contrast these two models, rats with or without perirhinal cortex lesions were compared across various conditions that controlled available information from specific sensory modalities. Intact rats not only showed visual, tactile, and olfactory recognition, but also overcame changes in the types of sensory information available between object sampling and subsequent object recognition, e.g., between sampling in the light and recognition in the dark, or vice versa. Perirhinal lesions severely impaired object recognition whenever visual cues were available, but spared olfactory recognition and tactile-based object recognition when tested in the dark. The perirhinal lesions also blocked the ability to recognize an object sampled in the light and then tested for recognition in the dark, or vice versa. The findings reveal parallel recognition systems for different senses reliant on distinct brain areas, e.g., perirhinal cortex for vision, but also show that: (1) recognition memory for multisensory stimuli involves competition between sensory systems and (2) perirhinal cortex lesions produce a bias to rely on vision, despite the presence of intact recognition memory systems serving other senses. PMID:21685150

  11. Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.

    PubMed

    Sirohi, Sunil; Walker, Brendan M

    2015-11-01

    Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive κ-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma-thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age-related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function.

  12. Enhanced stress-induced dopamine release in the prefrontal cortex of amphetamine-sensitized rats.

    PubMed

    Hamamura, T; Fibiger, H C

    1993-06-11

    This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross-sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization.

  13. Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

    PubMed

    Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

    2015-01-01

    Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation.

  14. Effects of oxotremorine on local glucose utilization in the rat cerebral cortex

    SciTech Connect

    Dam, M.; Wamsley, J.K.; Rapoport, S.I.; London, E.D.

    1982-08-01

    The (/sup 14/C)2-deoxy-D-glucose technique was used to examine the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in the cerebral cortex of the unanesthetized rat. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex. In the neocortex, OXO was more potent in elevating LCGU of the auditory, frontal, and sensorimotor regions compared with the visual cortex. Within these neocortical regions, OXO effects were greatest in cortical layers IV and V. OXO effects were more dramatic in the neocortex than in the meso- or paleocortex, and no significant effect occurred in the perirhinal and pyriform cortices. OXO-induced LCGU increases were not influenced by methylatropine (1 mg/kg, s.c.) but were antagonized completely by scopolamine (2.5 mg/kg, i.p.). Scopolamine reduced LCGU in layer IV of the auditory cortex and in the retrosplenial cortex. The distribution and magnitude of the cortical LCGU response to OXO apparently were related to the distributions of cholinergic neurochemical markers, especially high affinity muscarinic binding sites.

  15. Subplate neurons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex

    PubMed Central

    Tolner, Else A.; Sheikh, Aminah; Yukin, Alexey Y.; Kaila, Kai; Kanold, Patrick

    2012-01-01

    Patterned neuronal activity such as spindle bursts in the neonatal cortex is likely to promote the maturation of cortical synapses and neuronal circuits. Previous work on cats has shown that removal of subplate neurons, a transient neuronal population in the immature cortex, prevents the functional maturation of thalamocortical and intracortical connectivity. Here we studied the effect of subplate removal in the neonatal rat somatosensory cortex (S1). Using intracortical EEG we show that after selective removal of subplate neurons in the limb region of S1, endogenous and sensory evoked spindle burst activity is largely abolished. Consistent with the reduced in vivo activity in the S1 limb region, we find by in vitro recordings that thalamocortical inputs to layer 4 neurons are weak. In addition, we find that removal of subplate neurons in the S1 barrel region prevents the development of the characteristic histological barrel-like appearance. Thus, subplate neurons are crucially involved in the generation of particular types of early network activity in the neonatal cortex, which are an important feature of cortical development. The altered EEG pattern following subplate damage could be applicable in the neurological assessment of human neonates. PMID:22238105

  16. Organization of projections of rat retrosplenial cortex to the anterior thalamic nuclei.

    PubMed

    Shibata, H

    1998-10-01

    The organization of the projections from the retrosplenial cortex (Brodmann's area 29) to the anterior thalamic nuclei was examined in the rat with retrograde transport of the cholera toxin B subunit and anterograde transport of biotinylated dextran amine. Areas 29a and 29b project mainly ipsilaterally to the rostral two-thirds of the anteroventral nucleus, with area 29a projecting more rostrodorsally than area 29b. Area 29c projects bilaterally to the ventromedial part of the anteroventral nucleus. The projections from area 29c are organized in a topographic pattern such that the rostral area 29c projects to the caudoventral part of the anteroventral nucleus, whereas the caudal area 29c projects to the more rostrodorsal parts. Caudal area 29d projects mainly ipsilaterally to the rostrodorsal part of the anteromedial nucleus, and the rostral and dorsal parts of the anteroventral nucleus, whereas rostral area 29d projects bilaterally to the caudodorsal part of the anteromedial nucleus and the caudolateral part of the anteroventral nucleus. All the areas of the retrosplenial cortex provide sparse projections, mainly ipsilateral, to the anterodorsal nucleus, with a crude topographic pattern such that the rostrocaudal axis of the retrosplenial cortex corresponds to the caudorostral axis of the anterodorsal nucleus. The results indicate that each area of the retrosplenial cortex has a distinct projection field within the anterior thalamic nuclei. This suggests that each of these projections transmits distinct information that is important for complex memory and learning functions, e.g. discriminative avoidance learning and spatial memory.

  17. Vocalization-whisking coordination and multisensory integration of social signals in rat auditory cortex.

    PubMed

    Rao, Rajnish P; Mielke, Falk; Bobrov, Evgeny; Brecht, Michael

    2014-12-08

    Social interactions involve multi-modal signaling. Here, we study interacting rats to investigate audio-haptic coordination and multisensory integration in the auditory cortex. We find that facial touch is associated with an increased rate of ultrasonic vocalizations, which are emitted at the whisking rate (∼8 Hz) and preferentially initiated in the retraction phase of whisking. In a small subset of auditory cortex regular-spiking neurons, we observed excitatory and heterogeneous responses to ultrasonic vocalizations. Most fast-spiking neurons showed a stronger response to calls. Interestingly, facial touch-induced inhibition in the primary auditory cortex and off-responses after termination of touch were twofold stronger than responses to vocalizations. Further, touch modulated the responsiveness of auditory cortex neurons to ultrasonic vocalizations. In summary, facial touch during social interactions involves precisely orchestrated calling-whisking patterns. While ultrasonic vocalizations elicited a rather weak population response from the regular spikers, the modulation of neuronal responses by facial touch was remarkably strong.

  18. Embryonic amygdalar transplants in adult rats with motor cortex lesions: a molecular and electrophysiological analysis.

    PubMed

    Jiménez-Díaz, Lydia; Nava-Mesa, Mauricio O; Heredia, Margarita; Riolobos, Adelaida S; Gómez-Álvarez, Marcelo; Criado, José María; de la Fuente, Antonio; Yajeya, Javier; Navarro-López, Juan D

    2011-01-01

    Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host-graft connections. Nevertheless little is known about physiological properties or gene expression profiles of cortical implants with functional restorative capacity but no cortical origin. In this study, we show molecular and electrophysiological evidence supporting the functional development and integration of heterotopic transplants of embryonic amygdalar tissue placed into pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post-transplantation. Using reverse transcriptase quantitative polymerase chain reaction, we found that key glutamatergic, GABAergic, and muscarinic receptors transcripts were expressed at different quantitative levels both in grafted and host tissues, but were all continuously present in the graft. Parallel sharp electrode recordings of grafted neurons in brain slices showed a regular firing pattern of transplanted neurons similar to host amygdalar pyramidal neurons. Synaptic connections from the adjacent host cortex on grafted neurons were electrophysiologically investigated and confirmed our molecular results. Taken together, our findings indicate that grafted neurons from a non-cortical, non-motor-related, but ontogenetical similar source, not only received functionally effective contacts from the adjacent motor cortex, but also developed electrophysiological and gene expression patterns comparable to host pyramidal neurons; suggesting an interesting tool for the field of neural repair and donor tissue in adults.

  19. Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats.

    PubMed

    Alviña, Karina; Khodakhah, Kamran

    2008-05-15

    The cerebellum coordinates movement and maintains body posture. The main output of the cerebellum is formed by three deep nuclei, which receive direct inhibitory inputs from cerebellar Purkinje cells, and excitatory collaterals from mossy and climbing fibres. Neurons of deep cerebellar nuclei (DCN) are spontaneously active, and disrupting their activity results in severe cerebellar ataxia. It is suggested that voltage-gated calcium channels make a significant contribution to the spontaneous activity of DCN neurons, although the exact identity of these channels is not known. We sought to delineate the functional role and identity of calcium channels that contribute to pacemaking in DCN neurons of juvenile rats. We found that in the majority of cells blockade of calcium currents results in avid high-frequency bursting, consistent with the notion that the net calcium-dependent current in DCN neurons is outward. We showed that the bursting seen in these neurons after block of calcium channels is the consequence of reduced activation of small-conductance calcium-activated (SK) potassium channels. With the use of selective pharmacological blockers we showed that L-, P/Q-, R- and T-type calcium channels do not contribute to the spontaneous activity of DCN neurons. In contrast, blockade of high-threshold N-type calcium channels increased the firing rate and caused the cells to burst. Our results thus suggest a selective coupling of N-type voltage-gated calcium channels with calcium-activated potassium channels in DCN neurons. In addition, we demonstrate the presence of a cadmium-sensitive calcium conductance coupled with SK channels, that is pharmacologically distinct from L-, N-, P/Q-, R- and T-type calcium channels.

  20. A probabilistic atlas of the cerebellar white matter.

    PubMed

    van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

  1. [Properties of spontaneous and miniature excitatory postsynaptic currents of rat prefrontal cortex neurons].

    PubMed

    Malkin, S L; Kim, K Kh; Tikhonov, D B; Zaitsev, A V

    2014-01-01

    Quantum analysis of postsynaptic currents is important for fundamental and applied studies of synaptic transmission. In the present work, we investigated the possibility of using the characteristics of spontaneous excitatory postsynaptic currents (EPSCs) for estimation of quantum parameters of excitatory synaptic transmission in different types of neurons from rat prefrontal cortex slices. By blocking spontaneous spiking activity in slices by tetrodotoxin, we showed that spontaneous and miniature EPSCs in prefrontal cortex neurons did not differ by their properties. Thereby, both spontaneous and miniature responses can be used for estimation of quantum parameters of excitatory synaptic transmission in this preparation. We also revealed that excitatory spontaneous responses of pyramidal cells were 2 times lower by amplitude, had twice lower the coefficient of variation and exhibited much slower kinetics than responses of the fast-spiking and regular-spiking interneurons. Possible mechanisms of these differences are considered.

  2. Alteration of Rat Fetal Cerebral Cortex Development after Prenatal Exposure to Polychlorinated Biphenyls

    PubMed Central

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R. Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain. PMID:24642964

  3. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls.

    PubMed

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain.

  4. Decoding of the sound frequency from the steady-state neural activities in rat auditory cortex.

    PubMed

    Shiramatsu, Tomoyo I; Noda, Takahiro; Kanzaki, Ryohei; Takahashi, Hirokazu

    2013-01-01

    In the auditory cortex, onset activities have been extensively investigated as a cortical representation of sound information such as sound frequency. Yet, less attention has been paid to date to steady-state activities following the onset activities. In this study, we used machine learning to investigate whether steady-state activities in the presence of continuous sounds represent the sound frequency. Sparse Logistic Regression (SLR) decoded the sound frequency from band specific power or phase locking value (PLV) of local field potentials (LFP) from the fourth layer of the auditory cortex of anesthetized rats. Consequently, we found that SLR was able to decode the sound frequency from steady-state neural activities as well as onset activities. This result demonstrates that the steady-state activities contain information about the sound such as sound frequency.

  5. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    PubMed

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-01-11

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits.

  6. Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla.

    PubMed

    Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P

    2007-03-01

    Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.

  7. Adrenaline cells of the rat adrenal cortex and medulla contain renin and prorenin.

    PubMed

    Berka, J L; Kelly, D J; Robinson, D B; Alcorn, D; Marley, P D; Fernley, R T; Skinner, S L

    1996-05-31

    The distribution and content of renin in Sprague-Dawley (SD) and transgenic (mREN-2)27 rats (TG) were compared to further define the cellular basis and function of the adrenal renin-angiotensin system. Antibody binding (to rat and mouse renin protein and prosequence) was visualised in serial paraffin sections using an avidin-biotin peroxidase technique. Chromaffin and adrenaline cells were identified by tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase immunoreactivity, respectively. In SD zona glomerulosa (ZG), renin and its prosequence localised to small steroid cells while in homozygous (receiving lisinopril) and heterozygous (untreated) TG, steroid cells labelled in all cortical zones. In addition, throughout the cortex of each strain, large polyhedral adrenaline chromaffin cells occurring singly or in small groups and occasionally in rays labelled for renin and prosequence. Similar large adrenaline cells immunolabelled for all antisera in medulla while other cells were only TH-positive. Total adrenal renin content was 53 times higher in heterozygous transgenics than SD rats and was mainly (74%) prorenin. In SD, 37% of cortical renin was prorenin but in adrenal medulla only active renin was detected. Thus, from present and previous work both renin and prorenin occur not only in mitochondrial dense bodies of the ZG, but also in secretory granules of adrenaline chromaffin cells in both cortex and medulla implying in situ synthesis and paracrine functions.

  8. Hormetic Effects of Acute Methylmercury Exposure on Grp78 Expression in Rat Brain Cortex

    PubMed Central

    Zhang, Ye; Lu, Rongzhu; Liu, Wenshuai; Wu, Ying; Qian, Hai; Zhao, Xiaowu; Wang, Suhua; Xing, Guangwei; Yu, Feng; Aschner, Michael

    2013-01-01

    This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group (p < 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms. PMID:23549286

  9. GSK-3β inhibitors suppressed neuroinflammation in rat cortex by activating autophagy in ischemic brain injury.

    PubMed

    Zhou, Xiaogang; Zhou, Jian; Li, Xilei; Guo, Chang'an; Fang, Taolin; Chen, Zhengrong

    2011-07-29

    Previous studies have shown that GSK-3β inhibitor could reduce infarct volume after ischemia brain injury. However, the underlying mechanisms of GSK-3β inhibitor involving neuroprotection remain poorly understood. In the present study, we demonstrated that GSK-3β inhibitor suppressed insult-induced neuroinflammation in rat cortex by increasing autophagy activation in ischemic injury. Male rats were subjected to pMCAO (permanent middle cerebral artery occlusion) followed by treating with SB216763, a GSK-3β inhibitor. We found that insult-induced inflammatory response was significantly decreased by intraperitoneal infusion of SB216763 in rat cortex. A higher level of autophagy was also detected after SB216763 treatment. In the cultured primary microglia, SB216763 activated autophagy and suppressed inflammatory response. Importantly, inhibition of autophagy by Beclin1-siRNA increased inflammatory response in the SB216763-treated microglia. These data suggest that GSK-3β inhibitor suppressed neuroinflammation by activating autophagy after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

  10. Developmental hypothyroxinemia and hypothyroidism reduce proliferation of cerebellar granule neuron precursors in rat offspring by downregulation of the sonic hedgehog signaling pathway.

    PubMed

    Wang, Yuan; Wang, Yi; Dong, Jing; Wei, Wei; Song, Binbin; Min, Hui; Yu, Ye; Lei, Xibing; Zhao, Ming; Teng, Weiping; Chen, Jie

    2014-06-01

    Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during development result in dysfunction of the central nervous system, affecting psychomotor and motor function, although the underlying mechanisms causing these alterations are still unclear. Therefore, our aim is to study the effects of developmental hypothyroxinemia, caused by mild ID, and developmental hypothyroidism, caused by severe ID or methimazole (MMZ), on the proliferation of cerebellar granule neuron precursors (CGNPs), an excellent experimental model of cerebellar development and function. The sonic hedgehog (Shh) signaling pathway is essential for CGNP proliferation, and as such, its activation is also investigated here. A maternal hypothyroxinemia model was established in Wistar rats by administrating a mild ID diet, and two maternal hypothyroidism models were developed either by administrating a severe ID diet or MMZ water. Our results showed that hypothyroxinemia and hypothyroidism reduced proliferation of CGNPs on postnatal day (PN) 7, PN14, and PN21. Accordingly, the mean intensity of proliferating cell nuclear antigen and Ki67 nuclear antigen immunofluorescence was reduced in the mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of the Shh signaling pathway on PN7, PN14, and PN21. Our study supports the hypothesis that developmental hypothyroxinemia induced by mild ID, and hypothyroidism induced by severe ID or MMZ, reduce the proliferation of CGNPs, which may be ascribed to the downregulation of the Shh signaling pathway.

  11. Effect of fish oil intake on glucose levels in rat prefrontal cortex, as measured by microdialysis

    PubMed Central

    2013-01-01

    Background Brain glucose sensing may contribute to energy homeostasis control. The prefrontal cortex (PFC) participates in the hedonic component of feeding control. As high-fat diets may disrupt energy homeostasis, we evaluated in male Wistar rats whether intake of high-fat fish-oil diet modified cortical glucose extracellular levels and the feeding induced by intracerebroventricular glucose or PFC glucoprivation. Methods Glucose levels in PFC microdialysates were measured before and after a 30-min meal. Food intake was measured in animals receiving intracerebroventricular glucose followed, 30-min. later, by 2-deoxy-D-glucose injected into the PFC. Results The fish-oil group showed normal body weight and serum insulin while fat pads weight and glucose levels were increased. Baseline PFC glucose and 30-min. carbohydrates intake were similar between the groups. Feeding-induced PFC glucose levels increased earlier and more pronouncedly in fish-oil than in control rats. Intracerebroventricular glucose inhibited feeding consistently in the control but not in the fish-oil group. Local PFC glucoprivation with 2-DG attenuated glucose-induced hypophagia. Conclusions The present experiments have shown that, following food intake, more glucose reached the prefrontal cortex of the rats fed the high-fat fish-oil diet than of the rats fed the control diet. However, when administered directly into the lateral cerebral ventricle, glucose was able to consistently inhibit feeding only in the control rats. The findings indicate that, an impairment of glucose transport into the brain does not contribute to the disturbances induced by the high-fat fish-oil feeding. PMID:24369745

  12. The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning

    PubMed Central

    Nelson, A. J. D.; Hindley, E. L.; Pearce, J. M.; Vann, S. D.; Aggleton, J. P.

    2015-01-01

    The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information. PMID:25705182

  13. Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex.

    PubMed

    Pinto, Joshua G A; Jones, David G; Murphy, Kathryn M

    2013-01-01

    Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the

  14. Regulation of noradrenaline release from rat occipital cortex tissue chops by alpha 2-adrenergic agonists.

    PubMed

    Ong, M L; Ball, S G; Vaughan, P F

    1991-04-01

    Noradrenaline (NA) and the alpha 2-adrenergic agonists clonidine, BHT-920, and UK 14304-18 inhibit potassium-evoked release of [3H]NA from rat occipital cortex tissue chops with similar potencies. NA (10(-5) M) was most effective as up to 85% inhibition could be observed compared with 75%, 55%, and 35% for UK 14304-18, clonidine, and BHT-920, respectively, all at 10(-5) M. Potassium-evoked release was enhanced by both forskolin (10(-5) M) and 1 mM dibutyryl cyclic AMP. Pretreatment of tissue chops with 1 mM dibutyryl cyclic AMP in the presence of 3-isobutyl-1-methylxanthine partially reversed the alpha 2-adrenergic agonist inhibition of NA release. No reversal of inhibition was observed following pretreatment with 10(-5) M forskolin. The effects of clonidine, BHT-920, UK-14308-18, and NA on cyclic AMP formation stimulated by (a) forskolin, (b) isoprenaline, (c) adenosine, (d) potassium, and (e) NA were examined. Only cAMP formation stimulated by NA was inhibited by these alpha 2-adrenergic agonists. These results suggest that only a small fraction of adenylate cyclase in rat occipital cortex is coupled to alpha 2-adrenergic receptors. These results are discussed in relation to recent findings that several alpha 2-adrenergic receptor subtypes occur, not all of which are coupled to the inhibition of adenylate cyclase, and that alpha 2-adrenergic receptors inhibit NA release in rat occipital cortex by a mechanism that does not involve decreasing cyclic AMP levels.

  15. Short-term expansion of receptive fields in rat primary somatosensory cortex after hindpaw digit denervation.

    PubMed

    Byrne, J A; Calford, M B

    1991-11-29

    The immediate effect of changing the driving cutaneous input to locations within primary somatosensory cortex (SI) was examined by denervating one or more digits of the rat hindpaw by amputation or local anesthesia. When all or part of a receptive field of a cluster of neurons was denervated, it was found that the cortical location recorded from gained responsiveness to cutaneous stimulation of hindpaw areas bordering the denervated region. In 22 of the 29 animals studied this expansion took place within 5 min of the denervation.

  16. Characterization of hemodynamics and oxygenation in the renal cortex of rats

    NASA Astrophysics Data System (ADS)

    Grosenick, Dirk; Wabnitz, Heidrun; Macdonald, Rainer; Niendorf, Thoralf; Cantow, Kathleen; Flemming, Bert; Arakelyan, Karen; Seeliger, Erdmann

    2015-03-01

    We have performed a pre-clinical study on 13 rats to investigate the potential of near-infrared spectroscopy for quantification of hemoglobin concentration and oxygen saturation of hemoglobin in the renal cortex of small animals. These measurements were combined with laser-Doppler fluxmetry and a fluorescence quenching technique for quantification of tissue oxygen tension. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The methods were applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas.

  17. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    SciTech Connect

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  18. Myosin-V is present in synaptosomes from rat cerebral cortex.

    PubMed

    Mani, F; Espreafico, E M; Larson, R E

    1994-11-01

    The subcellular localization in brain of an unconventional, calmodulin-binding myosin (myosin-V) found in neurons, astrocytes and other secretory cells of vertebrates has been investigated by probing Western blots of synaptic fractions from rat cerebral cortex with affinity-purified polyclonal antibodies against myosin-V. Myosin-V was detected in intact synaptosomes and in lysed synaptosomes associated with a particulate fraction. Our data suggest a role for brain myosin-V in membrane-cytoskeleton function in the synaptic region.

  19. Chronic exposure of rats to occupational textile noise causes cytological changes in adrenal cortex.

    PubMed

    Oliveira, Maria Joao R; Monteiro, Mariana P; Ribeiro, Andreia M; Pignatelli, Duarte; Aguas, Artur P

    2009-01-01

    Chronic exposure to industrial noise and its effects on biological systems. Occupational exposure to noise may result in health disorders. Our aim was to evaluate the effects of chronic exposure to high-intensity noise of textile industry cotton rooms on the adrenal morphology. The environmental noise of a cotton-mill room from a large textile factory of Northern Portugal was recorded and reproduced by an adopted electroacoustic setup in a sound-insulated animal room where the rats were housed. The sounds were reproduced at the original levels of approximately 92 dB, which was achieved by equalization and distribution of sound output in the room. Wistar rats were submitted to noise exposure, in the same time schedule as employed in textile plants. After one, three, five, and seven months, the adrenals were collected and analyzed by light microscopy. Analyzed by multivariate analysis of variance and post hoc Bonferroni correction for multiple comparisons of the means between the groups. Noise exposure induced time-dependent changes in adrenal cortex, with decrease of zona fasciculata (ZF) and increase of zona reticularis volumes, together with a significant depletion of lipid droplet density in ZF cells of exposed rats, in comparison to control rats. Chronic exposure of rats to textile industry noise triggers cytological changes in the adrenals that suggest the existence of a sustained stress response.

  20. Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion.

    PubMed

    Pastuskovas, Cinthia V; Cassell, Martin D; Johnson, Alan Kim; Thunhorst, Robert L

    2003-04-01

    Insular cortex (IC) receives inputs from multiple sensory systems, including taste, and from receptors that monitor body electrolyte and fluid balance and blood pressure. This work analyzed metabolic activity of IC cells after water and sodium ingestion induced by sodium depletion. Rats were injected with the diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90 min, some rats received water and 0.3 M NaCl to drink for 2 h while others did not. A third group had access to water and saline but was not depleted of fluids. All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos-ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions of IC. Fluid-depleted rats without fluid access had significantly increased Fos-ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that drank water and sodium. Fos-ir levels were highest in anterior regions of IC and lowest in posterior regions of IC. These results implicate visceral, taste, and/or postingestional factors in the increased metabolic activity of cells in IC.

  1. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    PubMed

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  2. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    PubMed Central

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  3. Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex.

    PubMed

    Amaral, A C; Jakovcevski, M; McGaughy, J A; Calderwood, S K; Mokler, D J; Rushmore, R J; Galler, J R; Akbarian, S A; Rosene, D L

    2015-02-12

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.

  4. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    PubMed Central

    Hernández-Fonseca, Juan P.; Rincón, Jaimar; Pedreañez, Adriana; Viera, Ninoska; Arcaya, José L.; Carrizo, Edgardo; Mosquera, Jesús

    2009-01-01

    Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral. PMID:19812703

  5. Neuronal discharge patterns in the occipital cortex of developing rats during active and quiet sleep.

    PubMed

    Mirmiran, M; Corner, M

    1982-01-01

    Spontaneous action potentials were recorded at 1 mm depth (layer IV/V) in the occipital cortex of free moving rats between 8 and 60 days of postnatal age. Neuronal firing rates during quiet sleep (QS) increased sharply around day 11-12, parallel with an increase in the amplitude of EEG slow waves. The QS discharge pattern at all ages consisted of intermittent action potentials interspersed with short bursts. Active sleep (AS) from day 11-12 was characterized by longer lasting and more frequent bursts, and by a 2-3 X higher mean neuronal discharge rate than during QS. A peculiarity in 12-day-old rats was the presence of large fluctuations in overall firing rate continuously throughout sleep. Clomipramine completely abolished AS (for several hours) at all ages studied, during which time the cortical firing rates during sleep remained at (or lower than) the QS level prior to drug injection.

  6. The effect of GABA stimulation on GABAA receptor subunit protein and mRNA expression in rat cultured cerebellar granule cells.

    PubMed Central

    Platt, K. P.; Zwartjes, R. E.; Bristow, D. R.

    1996-01-01

    1. After 8 days in vitro, rat cerebellar granule cells were exposed to 1 mM gamma-aminobutyric acid (GABA) for periods of 1, 2, 4, 6, 8 and 10 days. The effect of the GABA exposure on GABAA receptor alpha 1, alpha 6 and beta 2,3 subunit protein expression and alpha 1 and alpha 6 subunit steady-state mRNA levels, was examined using Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. 2. GABA exposure for 2 days decreased alpha 1 (35 +/- 10%, mean +/- s.e.mean), beta 2,3 (21 +/- 9%) and alpha 6 (28 +/- 10%) subunit protein expression compared to control levels. The GABA-mediated reduction in alpha 1 subunit expression after 2 days treatment was abolished in the presence of the GABAA receptor antagonist, Ru 5135 (10 microM). 3. GABA exposure for 8 days increased alpha 1 (26 +/- 10%, mean +/- s.e.mean) and beta 2,3 (56 +/- 23%) subunit protein expression over control levels, whereas alpha 6 subunit protein expression remained below control levels (by 38 +/- 10%). However, after 10 days GABA exposure, alpha 6 subunit protein expression was also increased over control levels by 65 +/- 29% (mean +/- s.e.mean). 4. GABA exposure did not change the alpha 1 or alpha 6 subunit steady-state mRNA levels over and 8 day period, nor did it alter the expression of cyclophilin mRNA over 1-8 days. 5. These results suggest that chronic GABA exposure of rat cerebellar granule cells has a bi-phasic effect on GABAA receptor subunit expression that is independent of changes to mRNA levels. Therefore, the regulation of the GABAA receptor expression by chronic agonist treatment appears to involve post-transcriptional and/or post-translational processes. Images Figure 1 Figure 3 Figure 4 PMID:8968548

  7. Maternal thimerosal exposure results in aberrant cerebellar oxidative stress, thyroid hormone metabolism, and motor behavior in rat pups; sex- and strain-dependent effects.

    PubMed

    Sulkowski, Z L; Chen, T; Midha, S; Zavacki, A M; Sajdel-Sulkowska, Elizabeth M

    2012-06-01

    Methylmercury (Met-Hg) and ethylmercury (Et-Hg) are powerful toxicants with a range of harmful neurological effects in humans and animals. While Met-Hg is a recognized trigger of oxidative stress and an endocrine disruptor impacting neurodevelopment, the developmental neurotoxicity of Et-Hg, a metabolite of thimerosal (TM), has not been explored. We hypothesized that TM exposure during the perinatal period impairs central nervous system development, and specifically the cerebellum, by the mechanism involving oxidative stress. To test this, spontaneously hypertensive rats (SHR) or Sprague-Dawley (SD) rat dams were exposed to TM (200 μg/kg body weight) during pregnancy (G10-G15) and lactation (P5-P10). Male and female neonates were evaluated for auditory and motor function; cerebella were analyzed for oxidative stress and thyroid metabolism. TM exposure resulted in a delayed startle response in SD neonates and decreased motor learning in SHR male (22.6%), in SD male (29.8%), and in SD female (55.0%) neonates. TM exposure also resulted in a significant increase in cerebellar levels of the oxidative stress marker 3-nitrotyrosine in SHR female (35.1%) and SD male (14.0%) neonates. The activity of cerebellar type 2 deiodinase, responsible for local intra-brain conversion of thyroxine to the active hormone, 3',3,5-triiodothyronine (T3), was significantly decreased in TM-exposed SHR male (60.9%) pups. This coincided with an increased (47.0%) expression of a gene negatively regulated by T3, Odf4 suggesting local intracerebellar T3 deficiency. Our data thus demonstrate a negative neurodevelopmental impact of perinatal TM exposure which appears to be both strain- and sex-dependent.

  8. Speech training alters tone frequency tuning in rat primary auditory cortex.

    PubMed

    Engineer, Crystal T; Perez, Claudia A; Carraway, Ryan S; Chang, Kevin Q; Roland, Jarod L; Kilgard, Michael P

    2014-01-01

    Previous studies in both humans and animals have documented improved performance following discrimination training. This enhanced performance is often associated with cortical response changes. In this study, we tested the hypothesis that long-term speech training on multiple tasks can improve primary auditory cortex (A1) responses compared to rats trained on a single speech discrimination task or experimentally naïve rats. Specifically, we compared the percent of A1 responding to trained sounds, the responses to both trained and untrained sounds, receptive field properties of A1 neurons, and the neural discrimination of pairs of speech sounds in speech trained and naïve rats. Speech training led to accurate discrimination of consonant and vowel sounds, but did not enhance A1 response strength or the neural discrimination of these sounds. Speech training altered tone responses in rats trained on six speech discrimination tasks but not in rats trained on a single speech discrimination task. Extensive speech training resulted in broader frequency tuning, shorter onset latencies, a decreased driven response to tones, and caused a shift in the frequency map to favor tones in the range where speech sounds are the loudest. Both the number of trained tasks and the number of days of training strongly predict the percent of A1 responding to a low frequency tone. Rats trained on a single speech discrimination task performed less accurately than rats trained on multiple tasks and did not exhibit A1 response changes. Our results indicate that extensive speech training can reorganize the A1 frequency map, which may have downstream consequences on speech sound processing.

  9. Speech training alters tone frequency tuning in rat primary auditory cortex.

    PubMed

    Engineer, Crystal T; Perez, Claudia A; Carraway, Ryan S; Chang, Kevin Q; Roland, Jarod L; Kilgard, Michael P

    2013-10-24

    Previous studies in both humans and animals have documented improved performance following discrimination training. This enhanced performance is often associated with cortical response changes. In this study, we tested the hypothesis that long-term speech training on multiple tasks can improve primary auditory cortex (A1) responses compared to rats trained on a single speech discrimination task or experimentally naïve rats. Specifically, we compared the percent of A1 responding to trained sounds, the responses to both trained and untrained sounds, receptive field properties of A1 neurons, and the neural discrimination of pairs of speech sounds in speech trained and naïve rats. Speech training led to accurate discrimination of consonant and vowel sounds, but did not enhance A1 response strength or the neural discrimination of these sounds. Speech training altered tone responses in rats trained on six speech discrimination tasks but not in rats trained on a single speech discrimination task. Extensive speech training resulted in broader frequency tuning, shorter onset latencies, a decreased driven response to tones, and caused a shift in the frequency map to favor tones in the range where speech sounds are the loudest. Both the number of trained tasks and the number of days of training strongly predict the percent of A1 responding to a low frequency tone. Rats trained on a single speech discrimination task performed less accurately than rats trained on multiple tasks and did not exhibit A1 response changes. Our results indicate that extensive speech training can reorganize the A1 frequency map, which may have downstream consequences on speech sound processing.

  10. Chronic Ritalin Administration during Adulthood Increases Serotonin Pool in Rat Medial Frontal Cortex

    PubMed Central

    Daniali, Samira; Nahavandi, Arezo; Madjd, Zahra; Shahbazi, Ali; Niknazar, Somayeh; Shahbazzadeh, Delavar

    2013-01-01

    Background: Ritalin has high tendency to be abused. It has been the main indication to control attention deficit hyperactivity disorder. The college students may seek for it to improve their memory, decrease the need for sleep (especially during exams), which at least partially, can be related to serotonergic system. Therefore, it seems worthy to evaluate the effect of Ritalin intake on mature brain. There are many studies on Ritalin effect on developing brain, but only few studies on adults are available. This study was undertaken to find Ritalin effect on serotonin transporter (SERT) density in medial frontal cortex (MFC) of mature rat. Methods: Thirty male Wistar rats were used in the study. Rats were assigned into five groups (n = 6 per group): one control, two Ritalin and two vehicle groups. Twelve rats received Ritalin (20 mg/kg/twice a day) orally for eleven continuous days. After one week of withdrawal and another two weeks of rest, in order to evaluate short-term effects of Ritalin, six rats were sacrificed. Another six rats were studied to detect the long-term effects of Ritalin; therefore, they were sacrificed 12 weeks after the previous group. The immunohistochemistry was performed to evaluate the results. Results: Immunohistochemistry studies showed a higher density of SERT in both 2 and 12 weeks after withdrawal from Ritalin intake in MFC of rat and there was no significant difference between these two groups. Conclusions: Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period. PMID:23748891

  11. Speech training alters tone frequency tuning in rat primary auditory cortex

    PubMed Central

    Engineer, Crystal T.; Perez, Claudia A.; Carraway, Ryan S.; Chang, Kevin Q.; Roland, Jarod L.; Kilgard, Michael P.

    2013-01-01

    Previous studies in both humans and animals have documented improved performance following discrimination training. This enhanced performance is often associated with cortical response changes. In this study, we tested the hypothesis that long-term speech training on multiple tasks can improve primary auditory cortex (A1) responses compared to rats trained on a single speech discrimination task or experimentally naïve rats. Specifically, we compared the percent of A1 responding to trained sounds, the responses to both trained and untrained sounds, receptive field properties of A1 neurons, and the neural discrimination of pairs of speech sounds in speech trained and naïve rats. Speech training led to accurate discrimination of consonant and vowel sounds, but did not enhance A1 response strength or the neural discrimination of these sounds. Speech training altered tone responses in rats trained on six speech discrimination tasks but not in rats trained on a single speech discrimination task. Extensive speech training resulted in broader frequency tuning, shorter onset latencies, a decreased driven response to tones, and caused a shift in the frequency map to favor tones in the range where speech sounds are the loudest. Both the number of trained tasks and the number of days of training strongly predict the percent of A1 responding to a low frequency tone. Rats trained on a single speech discrimination task performed less accurately than rats trained on multiple tasks and did not exhibit A1 response changes. Our results indicate that extensive speech training can reorganize the A1 frequency map, which may have downstream consequences on speech sound processing. PMID:24344364

  12. Perirhinal cortex lesions uncover subsidiary systems in the rat for the detection of novel and familiar objects

    PubMed Central

    Albasser, Mathieu M; Amin, Eman; Iordanova, Mihaela D; Brown, Malcolm W; Pearce, John M; Aggleton, John P

    2011-01-01

    The present study compared the impact of perirhinal cortex lesions on tests of object recognition. Object recognition was tested directly by looking at the preferential exploration of novel objects over simultaneously presented familiar objects. Object recognition was also tested indirectly by presenting just novel objects or just familiar objects, and recording exploration levels. Rats with perirhinal cortex lesions were severely impaired at discriminating a novel object from a simultaneously presented familiar object (direct test), yet displayed normal levels of exploration to novel objects presented on their own and showed normal declines in exploration times for familiar objects that were repeatedly presented (indirect tests). This effective reduction in the exploration of familiar objects after perirhinal cortex lesions points to the sparing of some recognition mechanisms. This possibility led us to determine whether rats with perirhinal cortex lesions can overcome their preferential exploration deficits when given multiple object familiarisation trials prior to that same (familiar) object being paired with a novel object. It was found that after multiple familiarisation trials, objects could now successfully be recognised as familiar by rats with perirhinal cortex lesions, both following a 90-min delay (the longest delay tested) and when object recognition was tested in the dark after familiarisation trials in the light. These latter findings reveal: (i) the presumed recruitment of other regions to solve recognition memory problems in the absence of perirhinal cortex tissue; and (ii) that these additional recognition mechanisms require more familiarisation trials than perirhinal-based recognition mechanisms. PMID:21707792

  13. Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats

    PubMed Central

    Pérez-Valenzuela, Catherine; Gárate-Pérez, Macarena F.; Sotomayor-Zárate, Ramón; Delano, Paul H.; Dagnino-Subiabre, Alexies

    2016-01-01

    Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle

  14. Heterogeneity of histamine H3 receptor genomic expression in the cerebral cortex of spontaneously hypertensive rat.

    PubMed

    Shaw, J B; Cai, Q; Mtshali, C; Myles, E L; Washington, B

    2007-05-15

    Specific binding of [3H]-N-alpha-methylhistamine to homogenates from cerebral cortex tissue was analyzed in aged Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR). Scatchard plot analysis of [3H]-N-alpha-methylhistamine binding of the H3 receptor in the cerebral cortex from aged (6, 9, 12, and 16 week) SHR animals indicated that Bmax increased, respectively, 38.05 +/- 1.58, 59.63 +/- 2.48, 79.17 +/- 5.02, and 84.41 +/- 3.72 fmol/mg of protein. Binding studies using tissue from WKY rats indicated that maximal binding (Bmax) of the ligand to the receptor was not significantly altered. The analyses also yielded Kd values of 5, 7.2, 6.3 and 3.8 nM in SHR tissue respectively. Primers based on the sequence of the third intracellular loop of the H3 receptor were amplified at 35 cycles yielding several amplicons. These amplicons expressed sizes 875, 485, and 280 bp in 6 and 9 week cortical tissue from WKY animals where as in cortical tissue from 6 and 9 week SHR animals only two amplicons were expressed, 485 and 280 bp, respectively. Differences in gene expression for 12 and 16 week WKY and SHR rats were also compared using identical primers. Five amplicons were expressed in cortical tissue from 12 and 16 week WKY rats with 1000, 900, 821, 485, and 430 bp where as in 12 and 16 week SHR animals only one amplicon was expressed at 485 bp. The present results imply (1) that H3 receptor density in cortical tissue of SHR animals increases with age where as the number of the expressed amplicons of the detected H3 receptor decreases; and (2) even though a decrease in number of expressed amplicons of the H3 receptor were observed, an increase in expression of the larger amplicon (~500 bp) is evident.

  15. Early bilateral sensory deprivation blocks the development of coincident discharge in rat barrel cortex.

    PubMed

    Ghoshal, Ayan; Pouget, Pierre; Popescu, Maria; Ebner, Ford

    2009-02-25

    Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical postnatal period of cortical maturation, and severely reducing neural activity in a sensory pathway during this period could interfere with the development of coincident discharge among cortical neurons. Loss of such synchrony could provide a fundamental mechanism for the degradation of acuity shown in behavioral studies. We tested the hypothesis that synchronous discharge of barrel cortex neurons would fail to develop after sensory deprivation produced by bilateral whisker trimming from birth to postnatal day 60. By studying the correlated discharge of cortical neuron pairs, we found evidence for strong correlated firing in control animals, and this synchrony was almost absent among pairs of cortical barrel neurons in deprived animals. The degree of synchrony impairment was different in subregions of rat barrel cortex. The model that best fits the data is that cortical neurons receiving direct inputs from the primary sensory (lemniscal) pathway show the greatest decrement in synchrony following sensory deprivation, while neurons with diverse inputs from other areas of thalamus and cortex are relatively less affected in this dimension of cortical function.

  16. Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

    PubMed Central

    Liu, Albert; Jain, Neeraj; Vyas, Ajai; Lim, Lee Wei

    2015-01-01

    Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04803.001 PMID:25768425

  17. The serotonin reuptake inhibitor citalopram suppresses activity in the neonatal rat barrel cortex in vivo.

    PubMed

    Akhmetshina, Dinara; Zakharov, Andrei; Vinokurova, Daria; Nasretdinov, Azat; Valeeva, Guzel; Khazipov, Roustem

    2016-06-01

    Inhibition of serotonin uptake, which causes an increase in extracellular serotonin levels, disrupts the development of thalamocortical barrel maps in neonatal rodents. Previous in vitro studies have suggested that the disruptive effect of excessive serotonin on barrel map formation involves a depression at thalamocortical synapses. However, the effects of serotonin uptake inhibitors on the early thalamocortical activity patterns in the developing barrel cortex in vivo remain largely unknown. Here, using extracellular recordings of the local field potentials and multiple unit activity (MUA) we explored the effects of the selective serotonin reuptake inhibitor (SSRI) citalopram (10-20mg/kg, intraperitoneally) on sensory evoked activity in the barrel cortex of neonatal (postnatal days P2-5) rats in vivo. We show that administration of citalopram suppresses the amplitude and prolongs the delay of the sensory evoked potentials, reduces the power and frequency of the early gamma oscillations, and suppresses sensory evoked and spontaneous neuronal firing. In the adolescent P21-29 animals, citalopram affected neither sensory evoked nor spontaneous activity in barrel cortex. We suggest that suppression of the early thalamocortical activity patterns contributes to the disruption of the barrel map development caused by SSRIs and other conditions elevating extracellular serotonin levels.

  18. Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function.

    PubMed

    Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; de Boer, Sietse F; Koolhaas, Jaap M; Meerlo, Peter

    2017-02-01

    Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly the performance in a differential reinforcement of low rate responding (DRL) task, which is highly dependent upon an intact prefrontal cortex. Animals were trained to withhold a lever press until an imposed delay of 30 s after the last press had passed in order to achieve a food reward. Once the animals had mastered the task, they were sleep-restricted for 7 days with 20 h of sleep deprivation per day. At the end of each daily sleep deprivation session, performance on the DRL task was assessed. The results show that sleep-restricted animals were less able to time their responses correctly, started pressing the lever more randomly and showed signs of behavioural disinhibition, the latter possibly reflecting enhanced impulsivity. Our data support the hypothesis that a sleep debt has disruptive consequences for the functioning of the prefrontal cortex. This model offers possibilities for future studies investigating the underlying biochemical and molecular mechanisms of this relationship.

  19. The medial frontal cortex contributes to but does not organize rat exploratory behavior.

    PubMed

    Blankenship, Philip A; Stuebing, Sarah L; Winter, Shawn S; Cheatwood, Joseph L; Benson, James D; Whishaw, Ian Q; Wallace, Douglas G

    2016-11-12

    Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning.

  20. 3D reconstruction and standardization of the rat vibrissal cortex for precise registration of single neuron morphology.

    PubMed

    Egger, Robert; Narayanan, Rajeevan T; Helmstaedter, Moritz; de Kock, Christiaan P J; Oberlaender, Marcel

    2012-01-01

    The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain.

  1. Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex.

    PubMed

    Haj-Dahmane, S; Andrade, R

    1998-09-01

    The mammalian prefrontal cortex receives a dense cholinergic innervation from subcortical regions. We previously have shown that cholinergic stimulation of layer V pyramidal neurons of the rat prefrontal cortex results in a depolarization and the appearance of a slow afterdepolarization (sADP). In the current report we examine the mechanism underlying the sADP with the use of sharp microelectrode and whole cell recording techniques in in vitro brain slices. The ability of acetylcholine (ACh) and carbachol to induce the appearance of an sADP in pyramidal cells of layer V of prefrontal cortex is antagonized in a surmountable manner by atropine and is mimicked by application of muscarine or oxotremorine. These results indicate that ACh acts on muscarinic receptors to induce the sADP. In many cell types afterpotentials are triggered by calcium influx into the cell. Therefore we examined the possibility that calcium influx might be the trigger for the generation of the sADP. Consistent with this possibility, buffering intracellular calcium reduced or abolished the sADP but had little effect on the direct muscarinic receptor-induced depolarization also seen in these cells. These results, coupled to the previous observation that calcium channel blockers inhibit the sADP, indicated that the sADP results from a rise in intracellular calcium secondary to calcium influx into the cell. The ionic basis for the current underlying the sADP (IsADP) was examined with the use of ion substitution experiments. The amplitude of IsADP was found to be reduced in a graded fashion by replacement of extracellular sodium with N-methyl-D-glucamine (NMDG). In contrast no clear evidence for the involvement of potassium or chloride channels in the generation of the sADP or IsADP could be found. This result indicated that IsADP is carried by sodium ions flowing into the cell. However, the dependence of IsADP on extracellular sodium was less pronounced than expected for a pure sodium current. We

  2. Electrical stimulation of cerebellar fastigial nucleus promotes the expression of growth arrest and DNA damage inducible gene β and motor function recovery in cerebral ischemia/reperfusion rats.

    PubMed

    Liu, Bin; Li, Jianrui; Li, Longling; Yu, Lehua; Li, Changqing

    2012-06-27

    This study focused on the effects of electrical stimulation of cerebellar fastigial nucleus on the expression of growth arrest and DNA damage inducible gene β (Gadd45β) and on motor function recovery after focal cerebral ischemia/reperfusion (I/R) in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham I/R (control group), I/R (I/R group), I/R with sham stimulation and I/R with electrical stimulation at 6h, 12h, 24h, 2d and 3d after I/R. Cerebral ischemia and reperfusion was established by nylon monofilament occlusion method. Fastigial nucleus (FN) electrical stimulation was applied at 2h after ischemia for 1h. The changes in the expression of Gadd45β were analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and Western-blot respectively. Another group of rats were divided into the same 4 groups. Montoya staircase test score was used to test the motor function of affected forelimb. The levels of Gadd45β were significantly elevated after I/R injury. FN electrical stimulation treatment elevated the expression of Gadd45β further and improved motor function recovery. These results suggest that FN electrical stimulation can promote the expression of Gadd45β and motor function recovery after focal cerebral ischemia.

  3. Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery

    PubMed Central

    Nishibe, Mariko; Barbay, Scott; Guggenmos, David

    2010-01-01

    Abstract We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery. PMID:20873958

  4. Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats

    PubMed Central

    Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

    2016-01-01

    Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R2 = 0.42, respectively. We found that LFP signal on gamma frequency bands (30–120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications. PMID:27767063

  5. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

    PubMed

    Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

    2016-03-01

    This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

  6. Developmental alterations in noxious-evoked EEG activity recorded from rat primary somatosensory cortex.

    PubMed

    Devonshire, I M; Greenspon, C M; Hathway, G J

    2015-10-01

    Primary somatosensory cortex (S1) contains a nociceptive map that localizes potential tissue damage on the body and encodes stimulus intensity. An objective and specific biomarker of pain however is currently lacking and is urgently required for use in non-verbal clinical populations as well as in the validation of pre-clinical pain models. Here we describe studies to see if the responses of the S1 in juvenile rats are different to those in the adult. We recorded electroencephalogram (EEG) responses from S1 of lightly-anesthetized Sprague-Dawley rats at either postnatal day 21 or postnatal day 40 during the presentation of noxious (55 °C) or innocuous (30 °C) thermal stimuli applied to the plantar surface of the left hindpaw. The total EEG power across the recording period was the same in both ages after stimulation but the frequency distribution was significantly affected by age. Noxious heat evoked a significant increase in theta band (4-8 Hz) activity in adults only (P<0.0001 compared to baseline; P<0.0001 compared to juveniles). There were no significant differences in EEG responses to innocuous thermal stimuli. These data show that there are significant alterations in the processing of nociceptive inputs within the maturing cortex and that cortical theta activity is involved only in the adult cortical response to noxious stimulation.

  7. Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.

    PubMed

    Yates, J R; Darna, M; Beckmann, J S; Dwoskin, L P; Bardo, M T

    2016-01-28

    Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action.

  8. Proteomic analysis reveals differentially expressed proteins in the rat frontal cortex after methamphetamine treatment.

    PubMed

    Faure, J J; Hattingh, S M; Stein, D J; Daniels, W M

    2009-12-01

    Methamphetamine (MA) is an addictive psycho-stimulant and the illicit use of the drug is escalating. In the present study, we examined protein expression profiles in the rat frontal cortex exposed to a total of eight MA injections (1 mg/kg, intraperitoneal) using 2-DE based proteomics. We investigated protein changes occurring in both the cytosolic fraction and the membrane fraction. 2-DE analysis resulted in 62 cytosolic and 44 membrane protein spots that were differentially regulated in the frontal cortex of rats exposed to MA when compared to control animals. Of these spots, 47 cytosolic and 42 membrane proteins were identified respectively, using ESI-Quad-TOF, which included ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), beta-synuclein, 78 kDa glucose-regulated protein (GRP 78), gamma-enolase, dihydropyrimidase-related protein 2 (DRP 2), complexin 2 and synapsin II. These proteins are associated with protein degradation, redox regulation, energy metabolism, cellular growth, cytoskeletal modifications and synaptic function. Proteomic research may be useful in exploring the complex underlying molecular mechanisms of MA dependence.

  9. Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus.

    PubMed

    Veerasakul, Siriluk; Thanoi, Samur; Reynolds, Gavin P; Nudmamud-Thanoi, Sutisa

    2016-10-01

    Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.

  10. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats

    PubMed Central

    Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

    2016-01-01

    This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning. PMID:27051340

  11. Chronic infusions of GABA into the medial frontal cortex of the rat induce a reversible delayed spatial alternation deficit.

    PubMed

    Di Scala, G; Meneses, S; Brailowsky, S

    1990-10-30

    The effects of bilateral infusions of GABA into the medial frontal cortex of the rat were studied in a delayed spatial alternation task. It was found that GABA (500 mM, 1 microliter/h during 7 days) impaired the performance of the rats in the previously learned task. Upon interruption of the treatment, the animals rapidly recovered normal performance scores. The results show that GABA infusions produce functional deficits similar to those produced by lesions of the frontal cortex. Moreover, the deficits are reversible upon interruption of the treatment. This technique may therefore be a useful tool for studying frontal lobe functions and the involvement of GABAergic mechanisms in cognitive processes.

  12. Higher density of serotonin-1A receptors in the hippocampus and cerebral cortex of alcohol-preferring P rats

    SciTech Connect

    Wong, D.T.; Threlkeld, P.G. ); Lumeng, L.; Li, Ting-Kai )

    1990-01-01

    Saturable ({sup 3}H)-80HDPAT binding to 5HT-1A receptors in membranes prepared from hippocampus and frontal cerebral cortex of alcohol-preferring (P) rats and of alcohol-nonpreferring (NP) rats has been compared. The B{sub max} values or densities of recognition sites for 5HT-1A receptors in both brain areas of the P rats are 38 and 44 percent lower in the P rats than in the NP rats. The corresponding K{sub D} values are 38 and 44 percent lower in the P rats than in the NP rats, indicating higher affinities of the recognition sites for the 5HT-1A receptors in hippocampus and cerebral cortex of the P rats. These findings indicate either an enrichment of 5HT-1A receptor density during selective breeding for alcohol preference or an upregulation of 5HT-1A receptors of 5HT found in these brain areas of P rats as compared with the NP rats.

  13. Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations

    PubMed Central

    Sela, Yaniv; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Tononi, Giulio; Nir, Yuval

    2016-01-01

    Study Objectives: Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep. Methods: We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles. Results: We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150–250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity. Conclusions: Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms. Citation: Sela Y, Vyazovskiy VV, Cirelli C, Tononi G, Nir Y. Responses in rat core auditory cortex are preserved during sleep spindle oscillations. SLEEP 2016;39(5):1069–1082. PMID:26856904

  14. Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats.

    PubMed

    Bortel, Aleksandra; Nowak, Przemyslaw; Brus, Ryszard

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the locus coeruleus (LC). DSP-4 treatment of rats on the first and third days after birth produces a long-lasting lesion of noradrenergic neurons in the prefrontal cortex (PFC). In DSP-4-lesioned rats, studied as adults, we observed a decrease in norepinephrine content, with no significant change in the levels of dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA). There is now a well established interaction between noradrenergic and GABAergic systems, whereby the noradrenergic system is involved in the regulation of basal GABA release, while GABAergic neurons simultaneously exert tonic inhibitory regulation of LC norepinephrine neurons. We examined GABAergic neurotransmission in the norepinephrine-denervated PFC for a better appreciation of the interaction between these two systems. Treatment with the GABA transaminase inhibitor vigabatrine (VGB) increased the GABA level of PFC (tissue content) in both intact and lesioned groups. Additionally, VGB increased extracellular GABA concentration in the PFC in both control and DSP-4-lesioned animals, but the elevation of GABA was 2-fold higher in DSP-4 lesioned rats. These findings indicate that neonatal DSP-4 treatment increases GABAergic neurotransmission in the PFC of rats in adulthood, perhaps by decreasing reactivity of central GABA(A) receptors.

  15. Pioglitazone Ameliorates Neuron Loss in the Cortex after Aluminum-Treatment in Rats

    PubMed Central

    Rafati, Ali; Yazdani, Hajar; Noorafshan, Ali

    2015-01-01

    The objective was evaluation of the effects of pioglitazone on medial prefrontal cortex (mPFC) of the rats exposed to aluminum (Al). Al induces structural changes in several brain regions, including mPFC. Pioglitazone is an agonist of peroxisomal proliferator activated receptor gamma. Male rats were randomly assigned to control, Al-treated (10 mg/kg/day), and Al + PIO-treated groups (Al+ 40 mg/kg/day). After 56 days, the right mPFCs were removed. Then, the volume of mPFC and its subdivisions, volume of vessels, and total number of neurons and glia were estimated using stereological methods. The results showed 13–38% decrease in the volume of the mPFC and its subdivisions, mainly in the infralimbic region (P < 0.02). Besides, the volume of the vessels reduced by 47% after Al-treatment (P < 0.02). The total number of the neurons and glial cells was also reduced (40% and 25%, resp.) in the Al-exposed rats in comparison to the control ones (P < 0.02). Treatment of the animals with Al + PIO ameliorated the neuron loss and no improvement was seen in other parameters (P < 0.02). It can be concluded that treatment of the rats with PIO could ameliorate the neuron loss in the mPFC of the Al-treated animals. PMID:26167300

  16. Parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat: localization, morphology, connectivity and ultrastructure.

    PubMed

    Wouterlood, F G; Härtig, W; Brückner, G; Witter, M P

    1995-02-01

    We studied the distribution, morphology, ultrastructure and connectivity of parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat. Immunoreactive cell bodies were found in all layers of the entorhinal cortex except layer I. The highest numbers were observed in layers II and III of the dorsal division of the lateral entorhinal area whereas the lowest numbers occurred in the ventral division of the lateral entorhinal area. Most such neurons displayed multipolar configurations with smooth dendrites. We distinguished a type with long dendrites and a type with short dendrites. We also observed pyramidal immunoreactive neurons. A dense plexus of immunoreactive dendrites and axons was prominent in layers II and III of the dorsal division of the lateral entorhinal area and the medial entorhinal area. None of the parvalbumin-immunoreactive cells became retrogradely labelled after injection of horseradish peroxidase into the hippocampal formation. By electron microscopy, immunoreactivity was observed in cell bodies, dendrites, myelinated and unmyelinated axons and axon terminals. Immunoreactive dendrites and axons occurred in all cortical layers. We noted many myelinated immunoreactive axons. Immunoreactive axon terminals were medium sized, contained pleomorphic synaptic vesicles, and established symmetrical synapses. Both horseradish peroxidase labelled and unlabelled immunonegative cell bodies often received synapses from immunopositive axon terminals arranged in baskets. Synapses between immunoreactive axon terminals and unlabelled dendritic shafts and spines were abundant. Synapses with initial axon segments occurred less frequently. In addition, synaptic contacts were present between immunopositive axon terminals and cell bodies and dendrites. Thus, the several types of parvalbumin-containing neuron in the entorhinal cortex are interneurons, connected to one another and to immunonegative neurons through a network of synaptic contacts. Immunonegative

  17. Effect of the environment on the dendritic morphology of the rat auditory cortex.

    PubMed

    Bose, Mitali; Muñoz-Llancao, Pablo; Roychowdhury, Swagata; Nichols, Justin A; Jakkamsetti, Vikram; Porter, Benjamin; Byrapureddy, Rajasekhar; Salgado, Humberto; Kilgard, Michael P; Aboitiz, Francisco; Dagnino-Subiabre, Alexies; Atzori, Marco

    2010-02-01

    The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer-specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density.

  18. Dissociation of prefrontal cortex and nucleus accumbens dopaminergic systems in conditional learning in rats.

    PubMed

    George, David N; Jenkins, Trisha A; Killcross, Simon

    2011-11-20

    There is converging evidence that the prefrontal and mesolimbic dopaminergic (DAergic) systems are involved in the performance of a variety of tasks that require the use of contextual, or task-setting, information to select an appropriate response from a number of candidate responses. Performance on tasks of this nature are impaired in schizophrenia and in rats exposed to psychotomimetics; impairments that are often attenuated by administration of dopamine (DA) antagonists. Rats were trained on either a complex instrumental discrimination task, that required the use of task-setting cues, or a simple discrimination task that did not. Following training, microdialysis probes were implanted unilaterally in either the medial prefrontal cortex (mPFC) or nucleus accumbens (NAc) and samples were collected in freely moving animals during a behavioural test session. In Experiment 1, we found no difference in levels of DA in the mPFC of rats while they were performing the two discrimination tasks. Rats that performed the complex task did, however, show significantly higher mPFC DA levels relative to rats in the simple discrimination condition following the end of the behavioural test session. In Experiment 2, rats performing the conditional discrimination showed lower levels of DA in the NAc compared to the simple discrimination group both during the test session and after it. These results provide direct evidence that conditional discrimination tasks engage frontal and mesolimbic DAergic systems and are consistent with the proposal that regulation of fronto-striatal DA is involved in aspects of cognitive control that are known to be impaired in individuals with schizophrenia.

  19. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

    PubMed Central

    2012-01-01

    Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

  20. Sex-dependent changes in cerebellar thyroid hormone-dependent gene expression following perinatal exposure to thimerosal in rats.

    PubMed

    Khan, A; Sulkowski, Z L; Chen, T; Zavacki, A M; Sajdel-Sulkowska, E M

    2012-06-01

    Mammalian brain development is regulated by the action of thyroid hormone (TH) on target genes. We have previously shown that the perinatal exposure to thimerosal (TM, metabolized to ethylmercury) exerts neurotoxic effects on the developing cerebellum and is associated with a decrease in cerebellar D2 activity, which could result in local brain T3 deficiency. We have also begun to examine TM effect on gene expression. The objective of this study was to expand on our initial observation of altered cerebellar gene expression following perinatal TM exposure and to examine additional genes that include both TH-dependent as well as other genes critical for cerebellar development in male and female neonates exposed perinatally (G10-G15 and P5 to P10) to TM. We report here for the first time that expression of suppressor-of-white-apricot-1 (SWAP-1), a gene negatively regulated by T3, was increased in TM-exposed males (61.1% increase), but not in females; (p<0.05). Positively regulated T3-target genes, Purkinje cell protein 2 (Pcp2; p=0.07) and Forkhead box protein P4 (FoxP4; p=0.08), showed a trend towards decreased expression in TM-exposed males. The expression of deiodinase 2 (DIO2) showed a trend towards an increase in TM-exposed females, while deiodinase 3 (DIO3), transthyretin (TTR), brain derived neurotrophic factor (BDNF) and reelin (RELN) was not significantly altered in either sex. Since regulation of gene splicing is vital to neuronal proliferation and differentiation, altered expression of SWAP-1 may exert wide ranging effects on multiple genes involved in the regulation of cerebellar development. We have previously identified activation of another TH-dependent gene, outer dense fiber of sperm tails 4, in the TM exposed male pups. Together, these results also show sex-dependent differences between the toxic impacts of TM in males and females. Interestingly, the genes that were activated by TM are negatively regulated by TH, supporting our hypothesis of local

  1. Plasticity of cerebellar Purkinje cells in behavioral training of body balance control

    PubMed Central

    Lee, Ray X.; Huang, Jian-Jia; Huang, Chiming; Tsai, Meng-Li; Yen, Chen-Tung

    2015-01-01

    Neural responses to sensory inputs caused by self-generated movements (reafference) and external passive stimulation (exafference) differ in various brain regions. The ability to differentiate such sensory information can lead to movement execution with better accuracy. However, how sensory responses are adjusted in regard to this distinguishability during motor learning is still poorly understood. The cerebellum has been hypothesized to analyze the functional significance of sensory information during motor learning, and is thought to be a key region of reafference computation in the vestibular system. In this study, we investigated Purkinje cell (PC) spike trains as cerebellar cortical output when rats learned to balance on a suspended dowel. Rats progressively reduced the amplitude of body swing and made fewer foot slips during a 5-min balancing task. Both PC simple (SSs; 17 of 26) and complex spikes (CSs; 7 of 12) were found to code initially on the angle of the heads with respect to a fixed reference. Using periods with comparable degrees of movement, we found that such SS coding of information in most PCs (10 of 17) decreased rapidly during balance learning. In response to unexpected perturbations and under anesthesia, SS coding capability of these PCs recovered. By plotting SS and CS firing frequencies over 15-s time windows in double-logarithmic plots, a negative correlation between SS and CS was found in awake, but not anesthetized, rats. PCs with prominent SS coding attenuation during motor learning showed weaker SS-CS correlation. Hence, we demonstrate that neural plasticity for filtering out sensory reafference from active motion occurs in the cerebellar cortex in rats during balance learning. SS-CS interaction may contribute to this rapid plasticity as a form of receptive field plasticity in the cerebellar cortex between two receptive maps of sensory inputs from the external world and of efference copies from the will center for volitional movements

  2. Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.

    PubMed

    Insel, Nathan; Pilkiw, Maryna; Nobrega, José N; Hutchison, William D; Takehara-Nishiuchi, Kaori; Hamani, Clement

    2015-07-01

    Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.

  3. Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex.

    PubMed

    Geng, Kai-Wen; He, Ting; Wang, Rui-Rui; Li, Chun-Li; Luo, Wen-Jun; Wu, Fang-Fang; Wang, Yan; Li, Zhen; Lu, Yun-Fei; Guan, Su-Min; Chen, Jun

    2016-10-01

    Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether γ-aminobutyric acid A (GABAA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAA receptor agonist, or bicuculline, a selective GABAA receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAA receptors in the mPFC of rats.

  4. Role of NMDA receptors in noise-induced tau hyperphosphorylation in rat hippocampus and prefrontal cortex.

    PubMed

    Li, Kang; Jia, Hengchuan; She, Xiaojun; Cui, Bo; Zhang, Na; Chen, Xuewei; Xu, Chuanxiang; An, Gaihong; Ma, Qiang

    2014-05-15

    Chronic noise exposure has been associated with abnormalities in glutamate (Glu)-NMDAR signaling and tau hyperphosphorylation. However, further studies are necessary to clarify potential causal relationships. The aim of the present study was to evaluate the role of NMDA receptors in noise-induced tau hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar rats were randomly divided into three groups in the present study: control with isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d × 14d) and treated with saline (n=10); and noise exposure and treated with MK-801 (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202 and Ser396, and proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were measured in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We showed that phosphorylated tau levels were enhanced in noise-exposed-rat hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202 and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise-induced GSK3β overexpression but had no significant effect on PP2A levels. This suggests that MK-801 protects against chronic-noise-induced tau hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that Glu-NMDAR signaling may be involved in triggering aberrant tau hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.

  5. Selective cholinergic denervation of the cingulate cortex impairs the acquisition and performance of a conditional visual discrimination in rats.

    PubMed

    Winters, Boyer D; Robbins, Trevor W; Everitt, Barry J

    2004-01-01

    Results from excitotoxic lesion studies have implicated the cingulate cortex and its basal forebrain afferents in the acquisition and performance of conditional discrimination tasks. In the present work, we sought to clarify the role of specifically cholinergic projections from the vertical limb nucleus of the diagonal band (VDB) to the cingulate cortex in conditional visual discrimination (CVD) learning and performance in rats. We injected the cholinergic immunotoxin 192 IgG-saporin into the cingulate cortex to produce selective retrograde lesions of the cholinergic neurons projecting from the VDB to the cingulate cortex with the aim of sparing afferents of non-cingulate regions that can be disrupted by excitotoxic or immunotoxic VDB injections and non-cholinergic VDB projections that can also be damaged by excitotoxic lesions. Rats sustaining selective cholinergic denervation in this manner were significantly impaired relative to sham-operated animals in the acquisition and performance of a CVD rule of the type 'If lights are flashing FAST, press the left lever; if SLOW, press right'. Asymptotic performance of the lesion group was substantially lower than for control rats, indicating an enduring performance deficit. This impairment was associated with a selective disruption on trials with the FAST flashing stimulus. The results confirm the involvement of cholinergic innervation of the cingulate cortex in CVD performance; however, the nature of the deficit suggests a role for cholinergic modulation in task-relevant stimulus processing rather than stimulus-response learning per se.

  6. Cerebellar modules operate at different frequencies

    PubMed Central

    Zhou, Haibo; Lin, Zhanmin; Voges, Kai; Ju, Chiheng; Gao, Zhenyu; Bosman, Laurens WJ; Ruigrok, Tom JH; Hoebeek, Freek E

    2014-01-01

    Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions. DOI: http://dx.doi.org/10.7554/eLife.02536.001 PMID:24843004

  7. Regionalization of the isthmic and cerebellar primordia.

    PubMed

    Narboux-Nême, Nicolas; Louvi, Angeliki; Alexandre, Paula; Wassef, Marion

    2005-01-01

    The complex migrations of neurons born in the dorsal neural tube of the isthmic and rhombomere l (rl) domains complicate the delineation of the cerebellar primordium. We show that Purkinje cells (P) are likely generated over a wide territory before gathering in the future cerebellar primordium under the developing external granular layer. Later expansion of the cerebellum over a restricted ependymal domain could rely on mutual interations between P cells and granule cell progenitors (GCP). P are attracted by GCP and in turn stimulate their proliferation, increasing the surface of the developing cortex. At later stages, regionalization of the developing and adult cerebellar cortex can be detected through regional variations in the distribution of several P cell markers. Whether and how the developmental and adult P subtypes are related is still unknown and it is unclear if they delineate the same sets of cerebellar subdivisions. We provide evidence that the early P regionalization is involved in intrinsic patterning of the cerebellar primordium, in particular it relate to the organization of the corticonuclear connection. We propose that the early P regionalization provides a scaffold to the mature P regionalization but that the development of functional afferent connections induces a period of P plasticity during which the early regional identity of P could be remodeled.

  8. Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels

    PubMed Central

    Basille-Dugay, Magali; Vaudry, Hubert; Fournier, Alain; Gonzalez, Bruno; Vaudry, David

    2013-01-01

    High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) and a high density of PACAP binding sites have been detected in the developing rat cerebellum. In particular, PACAP receptors are actively expressed in immature granule cells, where they activate both adenylyl cyclase and phospholipase C. The aim of the present study was to investigate the ability of PACAP to induce calcium mobilization in cerebellar granule neurons. Administration of PACAP-induced a transient, rapid, and monophasic rise of the cytosolic calcium concentration ([Ca2+]i), while vasoactive intestinal peptide was devoid of effect, indicating the involvement of the PAC1 receptor in the Ca2+ response. Preincubation of granule cells with the Ca2+ ATPase inhibitor, thapsigargin, or the d-myo-inositol 1,4,5-trisphosphate (IP3) receptor antagonist, 2-aminoethoxydiphenyl borate, markedly reduced the stimulatory effect of PACAP on [Ca2+]i. Furthermore, addition of the calcium chelator, EGTA, or exposure of cells to the non-selective Ca2+ channel blocker, NiCl2, significantly attenuated the PACAP-evoked [Ca2+]i increase. Preincubation of granule neurons with the N-type Ca2+ channel blocker, ω-conotoxin GVIA, decreased the PACAP-induced [Ca2+]i response, whereas the L-type Ca2+ channel blocker, nifedipine, and the P- and Q-type Ca2+ channel blocker, ω-conotoxin MVIIC, had no effect. Altogether, these findings indicate that PACAP, acting through PAC1 receptors, provokes an increase in [Ca2+]i in granule neurons, which is mediated by both mobilization of calcium from IP3-sensitive intracellular stores and activation of N-type Ca2+ channel. Some of the activities of PACAP on proliferation, survival, migration, and differentiation of cerebellar granule cells could thus be mediated, at least in part, through these intracellular and/or extracellular calcium fluxes. PMID:23675369

  9. Methylmercury-Dependent Increases in Fluo4 Fluorescence in Neonatal Rat Cerebellar Slices Depend on Granule Cell Migrational Stage and GABAA Receptor Modulation

    PubMed Central

    Bradford, Aaron B.; Mancini, Jayme D.

    2016-01-01

    Methylmercury (MeHg) disrupts cerebellar function, especially during development. Cerebellar granule cells (CGC), which are particularly susceptible to MeHg by unknown mechanisms, migrate during this process. Transient changes in intracellular Ca2+ (Ca2+i) are crucial to proper migration, and MeHg is well known to disrupt CGC Ca2+i regulation. Acutely prepared slices of neonatal rat cerebellum in conjunction with confocal microscopy and fluo4 epifluorescence were used to track changes induced by MeHg in CGC Ca2+i regulation in the external (EGL) and internal granule cell layers (IGL) as well as the molecular layer (ML). MeHg caused no cytotoxicity but did cause a time-dependent increase in fluo4 fluorescence that depended on the stage of CGC development. CGCs in the EGL were most susceptible to MeHg-induced increases in fluo4 fluorescence. MeHg increased fluorescence in CGC processes but only diffusely; Purkinje cells rarely fluoresced in these slices. Neither muscimol nor bicuculline alone altered baseline fluo4 fluorescence in any CGC layer, but each delayed the onset and reduced the magnitude of effect of MeHg on fluo4 fluorescence in the EGL and ML. In the IGL, both muscimol and bicuculline delayed the onset of MeHg-induced increases in fluo4 fluorescence but did not affect fluorescence magnitude. Thus, acute exposure to MeHg causes developmental stage-dependent increases in Ca2+i in CGCs. Effects are most prominent in CGCs during development or early stages of migration. GABAA receptors participate in an as yet unclear manner to MeHg-induced Ca2+i dysregulation of CGCs. PMID:26514794

  10. Exposure to Music and Noise During Pregnancy Influences Neurogenesis and Thickness in Motor and Somatosensory Cortex of Rat Pups

    PubMed Central

    Kim, Chang-Hee; Lee, Sang-Chul; Shin, Je Wook; Chung, Kyung-Jin; Lee, Shin-Ho; Shin, Mal-Soon; Baek, Sang-Bin; Sung, Yun-Hee; Kim, Chang-Ju

    2013-01-01

    Purpose Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups. Methods The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth. Results Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex. Conclusions Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders. PMID:24143288

  11. Exposure to Extremely Low-Frequency Electromagnetic Fields Modulates Na+ Currents in Rat Cerebellar Granule Cells through Increase of AA/PGE2 and EP Receptor-Mediated cAMP/PKA Pathway

    PubMed Central

    Fang, Yan-Jia; Zhan, Xiao-Qin; Yao, Jin-Jing; Mei, Yan-Ai

    2013-01-01

    Although the modulation of Ca2+ channel activity by extremely low-frequency electromagnetic fields (ELF-EMF) has been studied previously, few reports have addressed the effects of such fields on the activity of voltage-activated Na+ channels (Nav). Here, we investigated the effects of ELF-EMF on Nav activity in rat cerebellar granule cells (GCs). Our results reveal that exposing cerebellar GCs to ELF-EMF for 10–60 min significantly increased Nav currents (INa) by 30–125% in a time- and intensity-dependent manner. The Nav channel steady-state activation curve, but not the steady-state inactivation curve, was significantly shifted (by 5.2 mV) towards hyperpolarization by ELF-EMF stimulation. This phenomenon is similar to the effect of intracellular application of arachidonic acid (AA) and prostaglandin E2 (PGE2) on INa in cerebellar GCs. Increases in intracellular AA, PGE2 and phosphorylated PKA levels in cerebellar GCs were observed following ELF-EMF exposure. Western blottings indicated that the NaV 1.2 protein on the cerebellar GCs membrane was increased, the total expression levels of NaV 1.2 protein were not affected after exposure to ELF-EMF. Cyclooxygenase inhibitors and PGE2 receptor (EP) antagonists were able to eliminate this ELF-EMF-induced increase in phosphorylated PKA and INa. In addition, ELF-EMF exposure significantly enhanced the activity of PLA2 in cerebellar GCs but did not affect COX-1 or COX-2 activity. Together, these data demonstrate for the first time that neuronal INa is significantly increased by ELF-EMF exposure via a cPLA2 AA PGE2 EP receptors PKA signaling pathway. PMID:23349866

  12. Effect of visual experience on tubulin synthesis during a critical period of visual cortex development in the hooded rat.

    PubMed

    Cronly-Dillon, J; Perry, G W

    1979-08-01

    1. In some species, restriction of visual experience in early life may affect normal functional development of visual cortical cells. The purpose of the present study was to determine if visual deprivation during post-natal development in the hooded rat also affects the production in brain cells of certain molecular components such as tubulin, that are needed for growth and maintenance of synapses and neurites. 2. Norwegian black hooded rats were reared under a variety of conditions of visual deprivation. At various stages of development the animals were killed and the rate of synthesis of tubulin in visual and motor cortex determined. Tritiated colchicine was used to assay tubulin and L-[14C]leucine injected into the brain ventricles 2 hr before death was used to measure rate of tubulin synthesis. 3. In rats reared in normal light there is a marked elevation in visual cortex tubulin synthesis that spans the period from eye-opening (13 days) until approximately 35 days. This elevation in tubulin synthesis is absent in animals reared in darkness from birth or deprived of pattern vision by eyelid suture. Also the effect of visual deprivation on tubulin synthesis was specifically confined to visual cortex and was not found for the motor cortex. Similarly, the incorporation of L-[14C]leucine into total protein in visual cortex was unaffected by dark rearing. Hence the stimulation of tubulin synthesis by visual experience in rat visual cortex is not attributable to a general non-specific stimulation of protein synthesis. 4. Rats that were dark-reared from birth and then exposed to a lighted environment for 24 hr during a certain critical period that extends from eye-opening (13 days) until approximately 35 days, displayed a significant increase in visual cortex tubulin rats that were brought into the light later than 35 days showed no significant increase in tubulin synthesis when compared with their continuously dark-rearer controls. 5. It is suggested that the number

  13. Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat.

    PubMed

    Hori, Nobuaki; Kadota, Tomoko; Akaike, Norio

    2015-01-01

    Chronic treatment of rats with methamphetamine (MAP) causes a range of functional changes to the central nervous system (CNS), including a toxicity that is widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In this report, we examined the effect of chronic MAP treatment on pyramidal neurons of the rat piriform cortex, an area involved in sensory processing, associative learning and a model system for studies on synaptic plasticity. MAP treatment significantly depolarized the membrane potential and decreased neuronal input resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses was disturbed by chronic MAP treatment, and the extent of long-term potentiation (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons were observed as blebbing of the dendrite trees. The changes we observed represent detrimental effects on the function of piriform cortical neurons further illustrating deficits in synaptic plasticity extend beyond the hippocampus. These changes may contribute to behavioural deficits in chronic MAP-treated animals.

  14. Bacopa monniera prevents from aluminium neurotoxicity in the cerebral cortex of rat brain.

    PubMed

    Jyoti, Amar; Sethi, Pallavi; Sharma, Deepak

    2007-04-20

    Bacopa monniera is a perennial herb, and is used as a nerve tonic in äyurveda, a traditional medicinal system in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate oxidative damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether Bacopa monniera could potentially inhibit aluminium toxicity in the cerebral cortex. Male Wister rats (8 months old) were administered with AlCl(3) orally at a dose of 50mg/kg/day in drinking water for 1 month. Experimental rats were given AlCl(3) along with Bacopa monniera extract at a dose of 40 mg/kg/day. One group of rats was treated with l-deprenyl at a dose of 1mg/kg/day along with AlCl(3) treatment. We have observed that Bacopa monniera prevented accumulation of lipid and protein damage significantly, which resulted from aluminium intake. Decline in the activity of endogenous antioxidant enzymes associated with aluminium administration was also inhibited by Bacopa monniera extract. The potential of Bacopa monniera to inhibit Al-induced oxidative stress was observed to be similar to that of l-deprenyl, which was taken as standard. The potential of Bacopa monniera extract to prevent aluminium neurotoxicity was reflected at the microscopic level as well, indicative of its neuroprotective effects. These findings strongly implicate that Bacopa monniera has potential to protect brain from oxidative damage resulting from aluminium toxicity.

  15. Neural correlates of object-associated choice behavior in the perirhinal cortex of rats.

    PubMed

    Ahn, Jae-Rong; Lee, Inah

    2015-01-28

    The perirhinal cortex (PRC) is reportedly important for object recognition memory, with supporting physiological evidence obtained largely from primate studies. Whether neurons in the rodent PRC also exhibit similar physiological correlates of object recognition, however, remains to be determined. We recorded single units from the PRC in a PRC-dependent, object-cued spatial choice task in which, when cued by an object image, the rat chose the associated spatial target from two identical discs appearing on a touchscreen monitor. The firing rates of PRC neurons were significantly modulated by critical events in the task, such as object sampling and choice response. Neuronal firing in the PRC was correlated primarily with the conjunctive relationships between an object and its associated choice response, although some neurons also responded to the choice response alone. However, we rarely observed a PRC neuron that represented a specific object exclusively regardless of spatial response in rats, although the neurons were influenced by the perceptual ambiguity of the object at the population level. Some PRC neurons fired maximally after a choice response, and this post-choice feedback signal significantly enhanced the neuronal specificity for the choice response in the subsequent trial. Our findings suggest that neurons in the rat PRC may not participate exclusively in object recognition memory but that their activity may be more dynamically modulated in conjunction with other variables, such as choice response and its outcomes.

  16. Proteomic analysis of rat cerebral cortex, hippocampus and striatum after exposure to morphine.

    PubMed

    Bierczynska-Krzysik, Anna; Pradeep John, Julius Paul; Silberring, Jerzy; Kotlinska, Jolanta; Dylag, Tomasz; Cabatic, Maureen; Lubec, Gert

    2006-10-01

    Although a series of proteins in the brain have been shown to be qualitatively or quantitatively dysregulated following morphine administration, a systematic proteomic study has not been carried out so far. We therefore aimed to show the effect of morphine on protein levels in the rat brain. For this purpose rats were given a morphine base in subcutaneously placed pellets and subsequently the cerebral cortex, hippocampus and striatum were taken for proteomic studies after three days. Extracted proteins were run on two-dimensional gel electrophoresis, scanned and quantified by specific software. Proteins with significantly different levels were analysed by mass spectrometry (MALDI-TOF-TOF). Twenty-six proteins were found to be differentially expressed and were unambiguously identified. Dysregulated proteins were from several protein pathways and cascades including signaling, metabolic, protein handling, antioxidant and miscellaneous classes. These findings represent an initial approach to the generation of a 'morphinome' and may form the basis for further protein chemical studies as a valuable analytical tool. Moreover, the study reveals morphine-regulated proteins in different brain areas and indicates the pathways involved following morphine administration in the rat, the main species for pharmacological studies in the field.

  17. Neural Correlates of Object-Associated Choice Behavior in the Perirhinal Cortex of Rats

    PubMed Central

    Ahn, Jae-Rong

    2015-01-01

    The perirhinal cortex (PRC) is reportedly important for object recognition memory, with supporting physiological evidence obtained largely from primate studies. Whether neurons in the rodent PRC also exhibit similar physiological correlates of object recognition, however, remains to be determined. We recorded single units from the PRC in a PRC-dependent, object-cued spatial choice task in which, when cued by an object image, the rat chose the associated spatial target from two identical discs appearing on a touchscreen monitor. The firing rates of PRC neurons were significantly modulated by critical events in the task, such as object sampling and choice response. Neuronal firing in the PRC was correlated primarily with the conjunctive relationships between an object and its associated choice response, although some neurons also responded to the choice response alone. However, we rarely observed a PRC neuron that represented a specific object exclusively regardless of spatial response in rats, although the neurons were influenced by the perceptual ambiguity of the object at the population level. Some PRC neurons fired maximally after a choice response, and this post-choice feedback signal significantly enhanced the neuronal specificity for the choice response in the subsequent trial. Our findings suggest that neurons in the rat PRC may not participate exclusively in object recognition memory but that their activity may be more dynamically modulated in conjunction with other variables, such as choice response and its outcomes. PMID:25632144

  18. The neurotensin agonist PD149163 increases Fos expression in the prefrontal cortex of the rat.

    PubMed

    Petrie, Kimberly A; Bubser, Michael; Casey, Cheryl D; Davis, M Duff; Roth, Bryan L; Deutch, Ariel Y

    2004-10-01

    Dopaminergic axons innervating the prefrontal cortex (PFC) target both pyramidal cells and GABAergic interneurons. Many of these dopamine (DA) axons in the rat coexpress the peptide neurotransmitter neurotensin. Previous electrophysiological data have suggested that neurotensin activates GABAergic interneurons in the PFC. Activation of D2-like DA receptors increases extracellular GABA levels in the PFC, as opposed to the striatum, where D2 receptor activation inhibits GABAergic neurons. Because activation of presynaptic D2 release-modulating autoreceptors in the PFC suppresses DA release but increases release of the cotransmitter neurotensin, D2 agonists may enhance the activity of GABAergic interneurons via release of neurotensin. In order to determine if neurotensin can activate GABAergic interneurons, we treated rats with the peptide neurotensin agonist, PD149163, and examined Fos expression in PFC neurons. Systemic administration of PD149163 increased overall Fos expression in the PFC, but not in the dorsal striatum. PD149163 induced Fos in PFC interneurons, as defined by the presence of calcium-binding proteins, and in pyramidal cells. Pretreatment with the high-affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos expression. These data suggest that neurotensin activates interneurons in the PFC of the rat.

  19. Entorhinal cortex contribution to contextual fear conditioning extinction and reconsolidation in rats.

    PubMed

    Baldi, Elisabetta; Bucherelli, Corrado

    2014-04-01

    During contextual fear conditioning a rat learns a temporal contiguity association between the exposition to a previously neutral context (CS) and an aversive unconditioned stimulus (US) as a footshock. This condition determines in the rat the freezing reaction during the subsequent re-exposition to the context. Potentially the re-exposition without US presentation initiates two opposing and competing processes: reconsolidation and extinction. Reconsolidation process re-stabilizes and strengthens the original memory and it is initiated by a brief re-exposure to context. Instead the extinction process leads to the decrease of the expression of the original memory and it is triggered by prolonged re-exposure to the context. Here we analyzed the entorhinal cortex (ENT) participation in contextual fear conditioning reconsolidation and extinction. The rats were trained in contextual fear conditioning and 24h later they were subjected either to a brief (2 min) reactivation session or to a prolonged (120 min) re-exposition to context to induce extinction of the contextual fear memory. Immediately after the reactivation or the extinction session, the animals were submitted to bilateral ENT TTX inactivation. Memory retention was assessed as conditioned freezing duration measured 72 h after TTX administration. The results showed that ENT inactivation both after reactivation and extinction session was followed by contextual freezing retention impairment. Thus, the present findings point out that ENT is involved in contextual fear memory reconsolidation and extinction. This neural structure might be part of parallel circuits underlying two phases of contextual fear memory processing.

  20. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    PubMed

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-03-23

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control (n = 36) and experimental (n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 weeks old in control and experimental groups (n = 9 per group per time point). Repeated-measures multivariate analysis of variance was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 weeks, but there was no significant difference between 9 and 11 weeks of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity.

  1. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

    PubMed

    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

  2. Chronic exposure of adult rats to low doses of methylmercury induced a state of metabolic deficit in the somatosensory cortex.

    PubMed

    Kong, Hang-Kin; Wong, Ming-Hung; Chan, Hing-Man; Lo, Samuel Chun-Lap

    2013-11-01

    Because of the ever-increasing bioaccumulation of methylmercury (MeHg) in the marine food chain, human consumers are exposed to low doses of MeHg continually through seafood consumption. Epidemiological studies strongly suggest that chronic prenatal exposure to nanomolar of MeHg has immense negative impacts on neurological development in neonates. However, effects of chronic exposure to low doses (CELDs) of MeHg in adult brains on a molecular level are unknown. The current study aims to investigate the molecular effects of CELD of MeHg on adult somatosensory cortex in a rat model using proteomic techniques. Young adult rats were fed with a low dose of MeHg (40 μg/kg body weight/day) for a maximum of 12 weeks. Whole proteome expression of the somatosensory cortex (S1 area) of normal rats and those with CELD to MeHg were compared. Levels of MeHg, total calcium, adenosine triphosphate (ATP), and pyruvate were also measured. Comparative proteomic studies of the somatosensory cortexes revealed that 94 proteins involved in the various metabolic processes (including carbohydrate metabolism, generation of precursors for essential metabolites, energy, proteins, cellular components for morphogenesis, and neurotransmission) were down-regulated. Consequently, levels of important end products of active metabolism including ATP, pyruvate, and total calcium were also found to be significantly reduced concomitantly. Our results showed that CELD of MeHg induced a state of metabolic deficit in the somatosensory cortex of adult rats.

  3. Neurotropic effect of exogenous L-carnosine in cultured slices of the olfactory cortex from rat brain.

    PubMed

    Khama-Murad, A X; Pavlinova, L I; Mokrushin, A A

    2008-07-01

    Incubation of cultured slices of the olfactory cortex from rat brain with L-carnosine in concentrations of 50, 250, and 500 M induced activation of glutamatergic and GABAB-ergic mechanisms and facilitated long-term posttetanic potentiation. The effect of L-carnosine is mediated by its effect on AMPA- and NMDA-related glutamatergic receptors and on inhibitory GABAB receptors.

  4. Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

    ERIC Educational Resources Information Center

    Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

    2014-01-01

    Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

  5. Neural Coding of Reward Magnitude in the Orbitofrontal Cortex of the Rat during a Five-Odor Olfactory Discrimination Task

    ERIC Educational Resources Information Center

    van Duuren, Esther; Nieto Escamez, Francisco A.; Joosten, Ruud N. J. M. A.; Visser, Rein; Mulder, Antonius B.; Pennartz, Cyriel M. A.

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory…

  6. Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

    PubMed

    Oza, Chintan S; Giszter, Simon F

    2015-05-06

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI.

  7. The perirhinal cortex of rats: an intricate area for microinfusion of anticonvulsants against soman-induced seizures.

    PubMed

    Myhrer, Trond; Enger, Siri; Aas, Pål

    2013-01-01

    Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide cannula in each hemisphere only invades a small area of this seizure controlling site in rats exposed to soman. The purpose of the present study was to examine whether infusions made through 2 cannulas in each perirhinal cortex may produce more efficacious anticonvulsant action against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP. The results showed that the mere presence of indwelling double cannulas caused proconvulsant effect in response to subsequent systemic administration of soman. Both the control and caramiphen groups with double cannulas had significantly shorter latencies to seizure onset than the corresponding groups with single cannula. Procyclidine resulted in anticonvulsant efficacy, even in rats with double cannulas. In rats that received twin infusions of DCG-IV or MPEP, the anticonvulsant impact was very high, inasmuch as a majority of the rats in each group was protected against seizure activity. Drugs possessing powerful anticonvulsant potency can apparently counteract the proconvulsant effect of double cannulas, and some can even gain enhanced anticonvulsant capacity when invading a larger area of the perirhinal cortex. Perirhinal EEG recordings (electrodes in indwelling cannulas) in a separate set of rats not exposed to soman or drugs showed no differences in basal electrical activity (total power 0.5-25Hz or the theta band 4-12Hz) between groups with single or double cannulas. The intrinsic excitability and synaptic connectivity of the perirhinal cortex may be associated with the proconvulsant impact observed in rats with double cannulas when exposed to soman.

  8. Somatosensory response properties of excitatory and inhibitory neurons in rat motor cortex.

    PubMed

    Murray, Peter D; Keller, Asaf

    2011-09-01

    In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.

  9. Rat whisker motor cortex is subdivided into sensory-input and motor-output areas

    PubMed Central

    Smith, Jared B.; Alloway, Kevin D.

    2013-01-01

    Rodent whisking is an exploratory behavior that can be modified by sensory feedback. Consistent with this, many whisker-sensitive cortical regions project to agranular motor [motor cortex (MI)] cortex, but the relative topography of these afferent projections has not been established. Intracortical microstimulation (ICMS) evokes whisker movements that are used to map the functional organization of MI, but no study has compared the whisker-related inputs to MI with the ICMS sites that evoke whisker movements. To elucidate this relationship, anterograde tracers were placed in posterior parietal cortex (PPC) and in the primary somatosensory (SI) and secondary somatosensory (SII) cortical areas so that their labeled projections to MI could be analyzed with respect to ICMS sites that evoke whisker movements. Projections from SI and SII terminate in a narrow zone that marks the transition between the medial agranular (AGm) and lateral agranular (AGl) cortical areas, but PPC projects more medially and terminates in AGm proper. Paired recordings of MI neurons indicate that the region between AGm and AGl is highly responsive to whisker deflections, but neurons in AGm display negligible responses to whisker stimulation. By contrast, AGm microstimulation is more effective in evoking whisker movements than microstimulation of the transitional region between AGm and AGl. The AGm region was also found to contain a larger concentration of corticotectal neurons, which could convey whisker-related information to the facial nucleus. These results indicate that rat whisker MI is comprised of at least two functionally distinct subregions: a sensory processing zone in the transitional region between AGm and AGl, and a motor-output region located more medially in AGm proper. PMID:23372545

  10. Developmental stability of taurine's activation on glycine receptors in cultured neurons of rat auditory cortex.

    PubMed

    Tang, Zheng-Quan; Lu, Yun-Gang; Chen, Lin

    2008-01-03

    Taurine is an endogenous amino acid that can activate glycine and/or gamma-aminobutyric acid type A (GABA(A)) receptors in the central nervous system. During natural development, taurine's receptor target undergoes a shift from glycine receptors to GABA(A) receptors in cortical neurons. Here, we demonstrate that taurine's receptor target in cortical neurons remains stable during in vitro development. With whole-cell patch-clamp recordings, we found that taurine always activated glycine receptors, rather than GABA(A) receptors, in neurons of rat auditory cortex cultured for 5-22 days. Our results suggest that the functional sensitivity of glycine and GABA(A) receptors to taurine is critically regulated by their developmental environments.

  11. Perirhinal cortex relays auditory information to the frontal motor cortices in the rat.

    PubMed

    Kyuhou, Shin-ichi; Matsuzaki, Ryuichi; Gemba, Hisae

    2003-12-26

    Auditory evoked potentials (AEPs) were recorded in the motor cortices (MC) with chronically implanted electrodes in the rat. Some of the AEPs in the MC, namely negative potentials on the surface and positive ones at a depth of 2 mm at latencies of about 50-150 ms, were abolished by limited bilateral lesions of the anterior perirhinal cortex (PERa) which was responsive to auditory stimulus, indicating that the AEPs in the MC were at least partially relayed in the PERa. The auditory response in the MC was prominently enhanced when water was supplied or the medial forebrain bundle was stimulated after auditory stimulus. These results indicate that the MC receives the reward associated auditory information from the PERa.

  12. Expression of the SNAT2 amino acid transporter during the development of rat cerebral cortex.

    PubMed

    Rodríguez, Angelina; Angelina, Rodríguez; Berumen, Laura C; Francisco, Zafra; Giménez, Cecilio; Cecilio, Giménez; García-Alcocer, María Guadalupe; Guadalupe, García-Alcocer María

    2011-11-01

    The sodium-coupled neutral amino acid transporter 2 (SNAT2) is a protein that is expressed ubiquitously in mammalian tissues and that displays Na(+), voltage and pH dependent activity. This transporter mediates the passage of small zwitterionic amino acids across the cell membrane and regulates the cell homeostasis and its volume. We have examined the expression of SNAT2 mRNA and protein during the development of the rat cerebral cortex, from gestation through the postnatal stages to adulthood. Our data reveal that SNAT2 mRNA and protein expression is higher during embryogenesis, while it subsequently diminishes during postnatal development. Moreover, during embryonic period SNAT2 colocalizes with the radial glial cells marker GLAST, while in postnatal period it is mainly detected in neuronal dendrites. These findings suggest a relevant role for amino acid transport through SNAT2 in the developing embryonic brain.

  13. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    NASA Astrophysics Data System (ADS)

    Vilensky, M. A.; Semyachkina-Glushkovskaya, Oxana V.; Timoshina, P. A.; Kuznetsova, Jana V.; Semyachkin-Glushkovskii, I. A.; Agafonov, Dmitry N.; Tuchin, Valerii V.

    2012-06-01

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  14. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

    PubMed

    Gainey, Melanie A; Wolfe, Renna; Pourzia, Olivia; Feldman, Daniel E

    2016-01-01

    Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  15. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    SciTech Connect

    Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A; Kuznetsova, Jana V; Semyachkin-Glushkovskii, I A; Agafonov, Dmitry N; Tuchin, Valerii V

    2012-06-30

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  16. [Effect of natural nootropic and adaptogen preparations on the cortex bioelectrical activity in rats].

    PubMed

    Suslov, N I; Churin, A A; Skurikhin, E G; Provalova, N V; Stal'bovskiĭ, A O; Litvinenko, V I; Dygaĭ, A M

    2002-01-01

    The influence of new nootrope and adaptogen preparations representing dry extracts from Scutellaria baicalensis (Georgi), Bergenia crassifolia (Fritsch), and velvet antlers of Siberian deer (Cervus elaphus sibiricus) on the bioelectric activity (cortex Fourier spectral EEG power) under conflict situation and conditioned reflex development was studied in rats. In both tests, the drugs produced similar changes in the EEG activity: (i) increase in the partial contribution of delta-activity and general spectral power, (ii) depression in the alpha and beta 1-rhythm power, (iii) depression of theta-activity in some cases. The EEG activity changes depended on the initial state and were closely connected with the behavior of the test animals. The drug administration led to normalization of the alpha and beta 1 activity correlated with the improved behavioral characteristics. At the same time, the delta activity was virtually not affected and lost the correlation with behavior.

  17. Developmental change and molecular properties of somatostatin receptors in the rat cerebral cortex

    SciTech Connect

    Kimura, N.

    1989-04-14

    The postnatal development and molecular properties of somatostatin receptor were studied in rat cerebral cortex. With (/sup 125/I-Tyr11)SRIF as a radiolabeled ligand, the specific ligand binding to crude membrane increased transiently in the early phase of postnatal development and then decreased. This increase of somatostatin binding was mainly due to the increased number of binding sites. The two subtypes classified by Tran et al., SSA and SSB, were confirmed and the studies on the relative amount of the subtypes revealed that more SSA subtype was expressed compared with SSB subtype during a week after birth, but, thereafter, both subtypes were almost equally expressed throughout the developmental stages tested. Molecular weight of the covalently labeled somatostatin receptor (SSA subtype), which was determined with the aid of the cross-linking agents, was estimated to be approximately 71,000 with no intramolecular disulfide bond.

  18. Simultaneous recording of rat auditory cortex and thalamus via a titanium-based, microfabricated, microelectrode device

    NASA Astrophysics Data System (ADS)

    McCarthy, P. T.; Rao, M. P.; Otto, K. J.

    2011-08-01

    Direct recording from sequential processing stations within the brain has provided opportunity for enhancing understanding of important neural circuits, such as the corticothalamic loops underlying auditory, visual, and somatosensory processing. However, the common reliance upon microwire-based electrodes to perform such recordings often necessitates complex surgeries and increases trauma to neural tissues. This paper reports the development of titanium-based, microfabricated, microelectrode devices designed to address these limitations by allowing acute recording from the thalamic nuclei and associated cortical sites simultaneously in a minimally invasive manner. In particular, devices were designed to simultaneously probe rat auditory cortex and auditory thalamus, with the intent of recording auditory response latencies and isolated action potentials within the separate anatomical sites. Details regarding the design, fabrication, and characterization of these devices are presented, as are preliminary results from acute in vivo recording.

  19. Pinealectomy increases ouabain high-affinity binding sites and dissociation constant in rat cerebral cortex.

    PubMed

    Acuña Castroviejo, D; del Aguila, C M; Fernández, B; Gomar, M D; Castillo, J L

    1991-06-24

    The effect of the pineal gland on the ouabain high-affinity binding sites (Kd = 3.1 +/- 0.4 nM, Bmax = 246.4 +/- 18.4 fmol/mg protein) in rat cerebral cortex was studied. Pinealectomy increased Bmax (940.7 +/- 42.8 fmol/mg protein) and Kd (7.6 +/- 1.5 nM) while melatonin injection (100 micrograms/kg b.wt.) counteracted these effects, restoring kinetic parameters (Kd = 1.9 +/- 0.05 nM; Bmax = 262.2 +/- 29.6 fmol/mg prot) to control values. Melatonin activity on ouabain binding in vitro did not depend upon a direct effect on the binding sites themselves. However, in competition experiments, melatonin increased binding affinity of ouabain as shown by the decreased IC50 values.

  20. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc.

  1. Energy metabolism in the rat cortex under thiopental anaesthesia measured In Vivo by (13) C MRS.

    PubMed

    Sonnay, Sarah; Duarte, João M N; Just, Nathalie; Gruetter, Rolf

    2017-03-19

    Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing (13) C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0.02 µmol/g/min, and the rate of the glutamate-glutamine cycle was 0.09 ± 0.02 µmol/g/min. In astrocytes, the TCA cycle rate was 0.16 ± 0.02 µmol/g/min, accounting for a quarter of whole brain glucose oxidation, pyruvate carboxylase rate was 0.02 ± 0.01 µmol/g/min, and glutamine synthetase was 0.12 ± 0.01 µmol/g/min. Relative to previous experiments under light α-chloralose anaesthesia, thiopental reduced oxidative metabolism in neurons and even more so in astrocytes. Interestingly, total oxidative metabolism in the cortex under thiopental anaesthesia surpassed the rate of pyruvate production by glycolysis, indicating substantial utilisation of substrates other than glucose, likely plasma lactate. © 2017 Wiley Periodicals, Inc.

  2. Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

    PubMed

    Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

    2017-03-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

  3. Sensory responses in the medial prefrontal cortex of anesthetized rats. Implications for sensory processing.

    PubMed

    Martin-Cortecero, Jesus; Nuñez, Angel

    2016-12-17

    The medial prefrontal cortex (mPFC) plays a key role in higher functions such as memory and attention. In order to demonstrate sensory responses in the mPFC, we used electrophysiological recordings of urethane-anesthetized rats to record somatosensory-evoked potentials (SEPs) or auditory-evoked potentials (AEPs) elicited by whisker deflections and click stimulation, respectively. Contralateral whisker stimulation or auditory stimuli were also applied to study sensory interference in the mPFC. Interference with other sensory stimuli or recent stimulation history reduced whisker responses in the infralimbic and prelimbic cortices of the ventral mPFC. This effect could be mediated by activation of parvalbumin (PV) interneurons since the effect was blocked by the P/Q calcium channel antagonist ω-agatoxin. In contrast, sensory interference or the recent stimulation history was not detected by the dorsal mPFC or the primary somatosensory cortex. Results obtained from retrograde tracer injections in the dorsal and ventral regions of the mPFC indicated that somatosensory and auditory sensory inputs may arrive at the dorsal mPFC through secondary sensory cortical areas, and through the insular and temporal cortical areas. The ventral mPFC may receive sensory information through the strong anatomical connections between the dorsal and ventral mPFC areas. In conclusion, results suggest mPFC plays an important role in sensory processing, which may have important implications in attentional and memory processes.

  4. A novel role for brain interleukin-6: facilitation of cognitive flexibility in rat orbitofrontal cortex.

    PubMed

    Donegan, Jennifer J; Girotti, Milena; Weinberg, Marc S; Morilak, David A

    2014-01-15

    Cytokines, small proteins released by the immune system to combat infection, are typically studied under inflammatory conditions. However, these molecules are also expressed in the brain in basal, nonpathological states, where they can regulate neuronal processes, such as learning and memory. However, little is known about how cytokine signaling in the brain may influence higher-order cognitive functions. Cognitive flexibility is one such executive process, mediated by the prefrontal cortex, which requires an adaptive modification of learned behaviors in response to environmental change. We explored the role of basal IL-6 signaling in the orbitofrontal cortex (OFC) in reversal learning, a form of cognitive flexibility that can be measured in the rat using the attentional set-shifting test. We found that inhibiting IL-6 or its downstream JAK/STAT signaling pathway in the OFC impaired reversal learning, suggesting that basal IL-6 and JAK/STAT signaling facilitate cognitive flexibility. Further, we demonstrated that elevating IL-6 in the OFC by adeno-associated virus-mediated gene delivery reversed a cognitive deficit induced by chronic stress, thus identifying IL-6 and the downstream JAK/STAT signaling pathway as potentially novel therapeutic targets for the treatment of stress-related psychiatric diseases associated with cognitive dysfunction.

  5. A Novel Role for Brain Interleukin-6: Facilitation of Cognitive Flexibility in Rat Orbitofrontal Cortex

    PubMed Central

    Donegan, Jennifer J.; Girotti, Milena; Weinberg, Marc S.

    2014-01-01

    Cytokines, small proteins released by the immune system to combat infection, are typically studied under inflammatory conditions. However, these molecules are also expressed in the brain in basal, nonpathological states, where they can regulate neuronal processes, such as learning and memory. However, little is known about how cytokine signaling in the brain may influence higher-order cognitive functions. Cognitive flexibility is one such executive process, mediated by the prefrontal cortex, which requires an adaptive modification of learned behaviors in response to environmental change. We explored the role of basal IL-6 signaling in the orbitofrontal cortex (OFC) in reversal learning, a form of cognitive flexibility that can be measured in the rat using the attentional set-shifting test. We found that inhibiting IL-6 or its downstream JAK/STAT signaling pathway in the OFC impaired reversal learning, suggesting that basal IL-6 and JAK/STAT signaling facilitate cognitive flexibility. Further, we demonstrated that elevating IL-6 in the OFC by adeno-associated virus-mediated gene delivery reversed a cognitive deficit induced by chronic stress, thus identifying IL-6 and the downstream JAK/STAT signaling pathway as potentially novel therapeutic targets for the treatment of stress-related psychiatric diseases associated with cognitive dysfunction. PMID:24431453

  6. State-dependent representation of amplitude-modulated noise stimuli in rat auditory cortex

    PubMed Central

    Marguet, Stephan L.; Harris, Kenneth D.

    2011-01-01

    Cortical responses can vary greatly between repeated presentations of an identical stimulus. Here we report that both trial-to-trial variability and faithfulness of auditory cortical stimulus representations depend critically on brain state. A frozen amplitude-modulated white noise stimulus was repeatedly presented while recording neuronal populations and local field potentials (LFPs) in auditory cortex of urethane-anesthetized rats. An information-theoretic measure was used to predict neuronal spiking activity from either the stimulus envelope or simultaneously recorded LFP. Evoked LFPs and spiking more faithfully followed high-frequency temporal modulations when the cortex was in a “desynchronized” state. In the “synchronized” state, neural activity was poorly predictable from the stimulus envelope, but the spiking of individual neurons could still be predicted from the ongoing LFP. Our results suggest that although auditory cortical activity remains coordinated as a population in the synchronized state, the ability of continuous auditory stimuli to control this activity is greatly diminished. PMID:21525282

  7. Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study.

    PubMed

    Demir, Ramazan; Acar, Goksemin; Tanriover, Gamze; Seval, Yasemin; Kayisli, Umit Ali; Agar, Aysel

    2005-01-01

    The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n = 12 for 10 days; CG-15, n = 12 for 15 days; CG-20, n=12 for 20 days). The three experimental groups (EG-10, n = 12; EG-15, n = 12; EG-20, n = 12) were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10), 15 days (EG-15) and 20 days (EG-20). Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (p < 0.05). However, synaptic density was significantly decreased in the experimental groups as compared to the control groups (p < 0.05). The results suggest that the excess of vitamin B6 intake causes damage to the cerebral cortex due to cellular intoxication and decreased synaptic density. Thus, careful attention should be paid to the time and dose of vitamin B6 recommended for patients who are supplemented with this vitamin.

  8. Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex.

    PubMed

    An, Shuming; Kilb, Werner; Luhmann, Heiko J

    2014-08-13

    Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage-sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory-evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination.

  9. Unbalanced synaptic inputs underlying multi-peaked frequency selectivity in rat auditory cortex.

    PubMed

    Zhou, Chang; Tao, Can; Zhang, Guangwei; Yan, Sumei; Wang, Lijuan; Zhou, Yi; Xiong, Ying

    2017-02-23

    By measuring the frequency selectivity at different intensities in the primary auditory cortex of adult rats, we found that a small group of cortical neurons can exhibit relatively weak but robust selectivity at multiple frequencies that are different from the most preferred frequency. Both in vivo multi-unit recordings (26/93 recordings) and single-unit recordings (16/137 neurons) confirmed that the preferred frequencies are periodic and have an averaged bandwidth (BW) of 0.3-0.4 octaves, which leads to multi-peaked frequency selectivity. Interestingly, the averaged bandwidth of the ripple in the frequency response tuning curve was invariant with the sound intensity. An investigation of the synaptic currents in vivo also revealed similar multi-peaked frequency selectivity for both excitation and inhibition. While the excitatory and inhibitory inputs were relatively balanced for most frequencies, the ratio between excitation and inhibition at the peak and valley of each ripple was highly unbalanced. Since this multi-peaked frequency selectivity can be observed at the synaptic, single-cell, and population levels, our results reveal a potential mechanism underlying the multi-peaked pattern of frequency selectivity in the primary auditory cortex.

  10. Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro.

    PubMed

    da Silva, Cleide G; Bueno, Ana Rúbia F; Schuck, Patrícia F; Leipnitz, Guilhian; Ribeiro, César A J; Rosa, Rafael B; Dutra Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir

    2004-01-01

    D-2-Hydroxyglutaric acid (DGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as D-2-hydroxyglutaric aciduria (DHGA). Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of DGA on total, cytosolic, and mitochondrial creatine kinase (CK) activities from cerebral cortex of 30-day-old Wistar rats. Total CK activity (tCK) was measured in whole cell homogenates, whereas cytosolic and mitochondrial activities were measured in the cytosolic and mitochondrial preparations from cerebral cortex. We verified that CK activities were significantly inhibited by DGA (11-34% inhibition) at concentrations as low as 0.25 mM, being the mitochondrial fraction the most affected activity. Kinetic studies revealed that the inhibitory effect of DGA was non-competitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of DGA on tCK activity is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of CK activity for brain metabolism homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA may be related to the neurodegeneration of patients affected by DHGA.

  11. Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy

    PubMed Central

    Zhang, Meng-Lin; Wang, Hong-Bo; Fu, Feng-Hua; Yu, Long-Chuan

    2017-01-01

    The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception. PMID:28378856

  12. Ventromedial prefrontal cortex regulates depressive-like behavior and rapid eye movement sleep in the rat.

    PubMed

    Chang, Celene H; Chen, Michael C; Qiu, Mei Hong; Lu, Jun

    2014-11-01

    Major depressive disorder (MDD) is a debilitating disease with symptoms like persistent depressed mood and sleep disturbances. The prefrontal cortex (PFC) has been implicated as an important structure in the neural circuitry of MDD, with pronounced abnormalities in blood flow and metabolic activity in PFC subregions, including the subgenual cingulate cortex (sgACC, or Brodmann area 25). In addition, deep brain stimulation in the sgACC has recently been shown to alleviate treatment-resistant depression. Depressed patients also show characteristic changes in sleep: insomnia, increased rapid-eye-movement (REM) sleep and shortened REM sleep latency. We hypothesized that sleep changes and depressive behavior may be a consequence of the abnormal PFC activity in MDD. The rat ventromedial PFC (vmPFC, prelimbic and infralimbic cortices) is considered to be the homolog of the human sgACC, so we examined the effect of excitotic lesions in the vmPFC on sleep-wake and depressive behavior. We also made lesions in the adjacent dorsal region (dmPFC) to compare the effect of this similar but distinct mPFC region. We found that both dmPFC and vmPFC lesions led to increased REM sleep, but only vmPFC-lesioned animals displayed increased sleep fragmentation, shortened REM latency and increased immobility in the forced swim test. Anatomic tracing suggests that the mPFC projects to the pontine REM-off neurons that interact with REM-on neurons in the dorsal pons. These results support our hypothesis that neuronal loss in the rat vmPFC resembles several characteristics of MDD and may be a critical area for modulating both mood and sleep.

  13. Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia.

    PubMed

    Cardell, M; Koide, T; Wieloch, T

    1989-06-01

    The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate was determined. In cortex from control animals, the rate of [1(-14)C]pyruvate decarboxylation was 9.6 +/- 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, significantly decreased blood glucose levels from 7.4 +/- 0.6 to 5.1 +/- 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 +/- 0.5 mumol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 +/- 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Modulation of the action of stress by ethanol on dopaminergic activity in the rat prefrontal cortex

    SciTech Connect

    Hegarty, A.A.; Vogel, W.H. )

    1992-02-26

    Both stress and ethanol, when administered individually, have been shown to affect dopamine (DA) and its metabolite (DOPAC) in the central nervous system. Stress can increase DA efflux in several areas of the brain, whereas ethanol has been shown to have variable effects on extracellular DA, either increasing DA or having no apparent effect. Furthermore, ethanol has been shown in microdissection studies to antagonize the effect of stress on the dopaminergic system, indicating an anxiety-reducing property of ethanol. However, the influence of the combination of stress and ethanol on the dopaminergic system has not been studied extensively with the newer technique of microdialysis. In this study, microdialysis was again used to characterize the interaction of immobilization stress and ethanol in the prefrontal cortex. Two groups of rats received either ethanol or saline in the resting state. A third group was immobilization stress and ethanol in the prefrontal cortex. Two groups of rats received either ethanol or saline in the resting state. A third group was immobilization Saline-treated animals showed essentially no changes in levels of DA or DOPAC. Ethanol had no effect on DA overflow in resting animals and caused only a small increase in DOPAC levels. Immobilization caused marked increases in DA levels and smaller increases in DOPAC. Ethanol pretreatment strongly reduced and antagonized the stress-induced increases in DA. However, ethanol potentiated the stress-induced increase in extracellular DOPAC. The authors data add biochemical evidence to the tension-reduction hypothesis of ethanol by perhaps implicating a reduction in the DA stress response by ethanol as a contributing factor in the development of alcoholism.

  15. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    PubMed

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease.

  16. Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex.

    PubMed

    Riga, Maurizio S; Teruel-Martí, Vicent; Sánchez, Connie; Celada, Pau; Artigas, Francesc

    2017-02-01

    Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg·day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n = 985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models.

  17. GABAergic mRNA expression is upregulated in the prefrontal cortex of rats sensitized to methamphetamine.

    PubMed

    Wearne, Travis A; Parker, Lindsay M; Franklin, Jane L; Goodchild, Ann K; Cornish, Jennifer L

    2016-01-15

    Inhibitory gamma-aminobutyric acid (GABA)-mediated neurotransmission plays an important role in the regulation of the prefrontal cortex (PFC), with increasing evidence suggesting that dysfunctional GABAergic processing of the PFC may underlie certain deficits reported across psychotic disorders. Methamphetamine (METH) is a psychostimulant that induces chronic psychosis in a subset of users, with repeat administration producing a progressively increased vulnerability to psychotic relapse following subsequent drug administration (sensitization). The aim here was to investigate changes to GABAergic mRNA expression in the PFC of rats sensitized to METH using quantitative polymerase chain reaction (qPCR). Male Sprague-Dawley rats (n=12) underwent repeated methamphetamine (intraperitoneal (i.p.) or saline injections for 7 days. Following 14 days of withdrawal, rats were challenged with acute methamphetamine (1mg/kg i.p.) and RNA was isolated from the PFC to compare the relative mRNA expression of a range of GABA enzymes, transporters and receptors subunits. METH challenge resulted in a significant sensitized behavioral (locomotor) response in METH pre-treated animals compared with saline pre-treated controls. The mRNAs of transporters (GAT1 and GAT3), ionotropic GABAA receptor subunits (α3 and β1), together with the metabotropic GABAB1 receptor, were upregulated in the PFC of sensitized rats compared with saline controls. These findings indicate that GABAergic mRNA expression is significantly altered at the pre and postsynaptic level following sensitization to METH, with sensitization resulting in the transcriptional upregulation of several inhibitory genes. These changes likely have significant consequences on GABA-mediated neurotransmission in the PFC and may underlie certain symptoms conserved across psychotic disorders, such as executive dysfunction.

  18. Distinct α- and β-band rhythms over rat somatosensory cortex with similar properties as in humans.

    PubMed

    Fransen, Anne M M; Dimitriadis, George; van Ede, Freek; Maris, Eric

    2016-06-01

    We demonstrate distinct α- (7-14 Hz) and β-band (15-30 Hz) rhythms in rat somatosensory cortex in vivo using epidural electrocorticography recordings. Moreover, we show in rats that a genuine β-rhythm coexists alongside β-activity that reflects the second harmonic of the arch-shaped somatosensory α-rhythm. This demonstration of a genuine somatosensory β-rhythm depends on a novel quantification of neuronal oscillations that is based on their rhythmic nature: lagged coherence. Using lagged coherence, we provide two lines of evidence that this somatosensory β-rhythm is distinct from the second harmonic of the arch-shaped α-rhythm. The first is based on the rhythms' spatial properties: the α- and β-rhythms are demonstrated to have significantly different topographies. The second is based on the rhythms' temporal properties: the lagged phase-phase coupling between the α- and β-rhythms is demonstrated to be significantly less than would be expected if both reflected a single underlying nonsinusoidal rhythm. Finally, we demonstrate that 1) the lagged coherence spectrum is consistent between signals from rat and human somatosensory cortex; and 2) a tactile stimulus has the same effect on the somatosensory α- and β-rhythms in both rats and humans, namely suppressing them. Thus we not only provide evidence for the existence of genuine α- and β-rhythms in rat somatosensory cortex, but also for their homology to the primate sensorimotor α- and β-rhythms.

  19. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    PubMed

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  20. Retrosplenial cortex lesions impair water maze strategies learning or spatial place learning depending on prior experience of the rat.

    PubMed

    Cain, Donald P; Humpartzoomian, Richard; Boon, Francis

    2006-06-30

    There has been debate whether lesions strictly limited to retrosplenial (RS) cortex impair spatial navigation, and how robust and reliable any such impairment is. The present study used a detailed behavioral analysis with naive or strategies-pretrained rats given RS lesions and trained in a water maze (WM). Naive RS lesioned rats failed to acquire the required WM strategies throughout training. Strategies-pretrained RS lesioned rats were specifically impaired in spatial place memory without a WM strategies impairment. Additional training overcame the spatial memory impairment. Thus the behavioral consequences of the lesion depend on the specific previous experience of the animal. The use of appropriate training and testing techniques has revealed experience-dependant dissociable impairments in WM strategies learning and in spatial memory, indicating that RS cortex is involved in both forms of learning.

  1. Tonotopic and Field-Specific Representation of Long-Lasting Sustained Activity in Rat Auditory Cortex

    PubMed Central

    Shiramatsu, Tomoyo I.; Noda, Takahiro; Akutsu, Kan; Takahashi, Hirokazu

    2016-01-01

    Cortical information processing of the onset, offset, and continuous plateau of an acoustic stimulus should play an important role in acoustic object perception. To date, transient activities responding to the onset and offset of a sound have been well investigated and cortical subfields and topographic representation in these subfields, such as place code of sound frequency, have been well characterized. However, whether these cortical subfields with tonotopic representation are inherited in the sustained activities that follow transient activities and persist during the presentation of a long-lasting stimulus remains unknown, because sustained activities do not exhibit distinct, reproducible, and time-locked responses in their amplitude to be characterized by grand averaging. To address this gap in understanding, we attempted to decode sound information from densely mapped sustained activities in the rat auditory cortex using a sparse parameter estimation method called sparse logistic regression (SLR), and investigated whether and how these activities represent sound information. A microelectrode array with a grid of 10 × 10 recording sites within an area of 4.0 mm × 4.0 mm was implanted in the fourth layer of the auditory cortex in rats under isoflurane anesthesia. Sustained activities in response to long-lasting constant pure tones were recorded. SLR then was applied to discriminate the sound-induced band-specific power or phase-locking value from those of spontaneous activities. The highest decoding performance was achieved in the high-gamma band, indicating that cortical inhibitory interneurons may contribute to the sparse tonotopic representation in sustained activities by mediating synchronous activities. The estimated parameter in the SLR decoding revealed that the informative recording site had a characteristic frequency close to the test frequency. In addition, decoding of the four test frequencies demonstrated that the decoding performance of the SLR

  2. TRANSPORT AND METABOLISM OF THIAMINE IN RAT BRAIN CORTEX IN VITRO.

    PubMed

    SHARMA, S K; QUASTEL, J H

    1965-03-01

    1. Aerobic incubation at 37 degrees of rat brain-cortex slices in Krebs-Ringer phosphate medium containing glucose and labelled thiamine results in accumulation in the tissue of labelled thiamine and labelled thiamine phosphates. The concentration of the labelled thiamine in the tissue cell water increases with increase of external labelled thiamine concentration in an approximately linear manner, the concentration ratio for labelled thiamine (tissue:medium) exceeding unity with low external thiamine concentrations (e.g. 0.2mum) and diminishing to about unity as the external thiamine concentration is increased to 1mum. The concentration of labelled phosphorylated thiamine in the tissue is at least double that of the labelled thiamine present and its amount increases with increase of external thiamine concentration. Labelled phosphorylated thiamine appears in the medium, its amount being about one-fifteenth of that in the tissue. Phosphorylation of thiamine in the tissue proceeds during incubation for 3hr. and, with an external labelled thiamine concentration of 0.2mum, about 48% conversion of thiamine takes place. 2. In the presence of ouabain (0.1mm), which does not inhibit thiamine phosphorylation in rat brain extract, there is a fall in the uptake of labelled thiamine by brain-cortex slices and the concentration ratio for the labelled thiamine (tissue:medium) falls to below unity. Anaerobiosis, lack of Na(+) or the presence of Amprol (0.01mm) leads to marked inhibition of thiamine phosphorylation, and the concentration ratio for labelled thiamine (tissue:medium) falls to about unity. The facts lead to the conclusion that thiamine is conveyed into the brain cell against a concentration gradient by an energy-assisted process mediated by a membrane carrier. Pyri-thiamine is a marked inhibitor of thiamine phosphorylation in brain extract. 3. Thiamine monophosphate and thiamine diphosphate inhibit thiamine phosphorylation in brain extract. They diminish ;total

  3. Hidden prenatal malnutrition in the rat: role of β₁-adrenoceptors on synaptic plasticity in the frontal cortex.

    PubMed

    Flores, Osvaldo; Pérez, Hernán; Valladares, Luis; Morgan, Carlos; Gatica, Arnaldo; Burgos, Héctor; Olivares, Ricardo; Hernández, Alejandro

    2011-10-01

    Moderate reduction in the protein content of the mother's diet (hidden malnutrition) does not alter body and brain weights of rat pups at birth, but leads to dysfunction of neocortical noradrenaline systems together with impaired long-term potentiation and visuo-spatial memory performance. As β₁-adrenoceptors and downstream protein kinase signaling are critically involved in synaptic long-term potentiation and memory formation, we evaluated the β₁-adrenoceptor density and the expression of cyclic-AMP dependent protein kinase, calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the frontal cortex of prenatally malnourished adult rats. In addition, we also studied if β₁-adrenoceptor activation with the selective β₁ agonist dobutamine could improve deficits of prefrontal cortex long-term potentiation presenting these animals. Prenatally malnourished rats exhibited half of β₁-adrenoceptor binding, together with a 51% and 65% reduction of cyclic AMP-dependent protein kinase α and calcium/calmodulin-dependent protein kinase α expression, respectively, as compared with eutrophic animals. Administration of the selective β₁ agonist dobutamine prior to tetanization completely rescued the ability of the prefrontal cortex to develop and maintain long-term potentiation in the malnourished rats. Results suggest that under-expression of neocortical β₁-adrenoceptors and protein kinase signaling in hidden malnourished rats functionally affects the synaptic networks subserving prefrontal cortex long-term potentiation. β₁-adrenoceptor activation was sufficient to fully recover neocortical plasticity in the PKA- and calcium/calmodulin-dependent protein kinase II-deficient undernourished rats, possibly by producing extra amounts of cAMP and/or by recruiting alternative signaling cascades.

  4. Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

    PubMed

    Li, Zhen; Lu, Yun-Fei; Li, Chun-Li; Wang, Yan; Sun, Wei; He, Ting; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

  5. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    PubMed

    Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  6. Anti-oxidative effects produced by environmental enrichment in the hippocampus and cerebral cortex of male and female rats.

    PubMed

    Mármol, Frederic; Rodríguez, Clara A; Sánchez, Juan; Chamizo, Victoria D

    2015-07-10

    Both physical and intellectual activity may reduce the incidence of neurodegenerative disorders. There is evidence that environmental enrichment (EE) can induce profound behavioral, neurochemical and neuroanatomical changes, thus producing lasting improvements in memory and learning tasks. In this study we evaluated the anti-oxidative effects produced by EE in the hippocampus and the cerebral cortex of male and female rats. The animals had been reared in either EE or control conditions. The parameters studied were: thiobarbituric acid reactive substances (TBARS), protein oxidation, total radical antioxidant parameter, catalase, superoxide dismutase and superoxide anion activity. The results showed that our EE protocol reduced markers of oxidative stress in the hippocampus and in the cerebral cortex. Overall, the measures taken in the two cerebral regions revealed that EE rats showed higher values for antioxidant measures and lower values for oxidative stress parameters than control animals. More importantly, a consistent sex difference was found, indicating that in female rats the hippocampus and cerebral cortex are plastic brain regions receptive to external stimulation such as EE. Although EE males have higher levels for antioxidant capacity, catalase and SOD, it is likely that females do not need to activate all the antioxidant defenses since they have a greater capacity to assimilate external stimuli. This is suggested by the similarity of protein oxidation and TBARS levels in hippocampus in both sexes, and the even lower levels of protein oxidation and superoxide anion activity in the cerebral cortex in EE females.

  7. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    PubMed Central

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately. PMID:27785113

  8. The involvement of Nek2 and Notch in the proliferation of rat adrenal cortex triggered by POMC-derived peptides.

    PubMed

    de Mendonca, Pedro Omori Ribeiro; Costa, Ismael Cabral; Lotfi, Claudimara Ferini Pacicco

    2014-01-01

    The adrenal gland is a dynamic organ that undergoes constant cell turnover. This allows for rapid organ remodeling in response to the physiological demands of the HPA axis, which is controlled by proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH) and N-Terminal peptides (N-POMC). In the rat adrenal cortex, POMC-derived peptides trigger a mitogenic effect, and this process increases cyclins D and E, while inhibiting p27Kip1. The goal of the present study was to further explore the mitogenic effect of ACTH and synthetic N-POMC1-28 peptides by investigating the differences in the expression of key genes involved in the cell cycle of the rat adrenal cortex, following inhibition of the HPA axis. Moreover, we evaluated the differences between the inner and outer fractions of the adrenal cortex (ZF-fraction and ZG-fraction) in terms of their response patterns to different stimuli. In the current study, the inhibition of the HPA axis repressed the expression of Ccnb2, Camk2a, and Nek2 genes throughout the adrenal cortex, while treatments with POMC-derived peptides stimulated Nek2, gene and protein expression, and Notch2 gene expression. Furthermore, Notch1 protein expression was restricted to the subcapsular region of the cortex, an area of the adrenal cortex that is well-known for proliferation. We also showed that different regions of the adrenal cortex respond to HPA-axis inhibition and to induction with POMC-derived peptides at different times. These results suggest that cells in the ZG and ZF fractions could be at different phases of the cell cycle. Our results contribute to the understanding of the mechanisms involved in cell cycle regulation in adrenocortical cells triggered by N-POMC peptides and ACTH, and highlight the involvement of genes such as Nek2 and Notch.

  9. The Development of Nociceptive Network Activity in the Somatosensory Cortex of Freely Moving Rat Pups

    PubMed Central

    Chang, P.; Fabrizi, L.; Olhede, S.; Fitzgerald, M.

    2016-01-01

    Cortical perception of noxious stimulation is an essential component of pain experience but it is not known how cortical nociceptive activity emerges during brain development. Here we use continuous telemetric electrocorticogram (ECoG) recording from the primary somatosensory cortex (S1) of awake active rat pups to map functional nociceptive processing in the developing brain over the first 4 weeks of life. Cross-sectional and longitudinal recordings show that baseline S1 ECoG energy increases steadily with age, with a distinctive beta component replaced by a distinctive theta component in week 3. Event-related potentials were evoked by brief noxious hindpaw skin stimulation at all ages tested, confirming the presence of functional nociceptive spinothalamic inputs in S1. However, hindpaw incision, which increases pain sensitivity at all ages, did not increase S1 ECoG energy until week 3. A significant increase in gamma (20–50 Hz) energy occurred in the presence of skin incision at week 3 accompanied by a longer-lasting increase in theta (4–8 Hz) energy at week 4. Continuous ECoG recording demonstrates specific postnatal functional stages in the maturation of S1 cortical nociception. Somatosensory cortical coding of an ongoing pain “state” in awake rat pups becomes apparent between 2 and 4 weeks of age. PMID:27797835

  10. Spike count, spike timing and temporal information in the cortex of awake, freely moving rats

    NASA Astrophysics Data System (ADS)

    Scaglione, Alessandro; Foffani, Guglielmo; Moxon, Karen A.

    2014-08-01

    Objective. Sensory processing of peripheral information is not stationary but is, in general, a dynamic process related to the behavioral state of the animal. Yet the link between the state of the behavior and the encoding properties of neurons is unclear. This report investigates the impact of the behavioral state on the encoding mechanisms used by cortical neurons for both detection and discrimination of somatosensory stimuli in awake, freely moving, rats. Approach. Neuronal activity was recorded from the primary somatosensory cortex of five rats under two different behavioral states (quiet versus whisking) while electrical stimulation of increasing stimulus strength was delivered to the mystacial pad. Information theoretical measures were then used to measure the contribution of different encoding mechanisms to the information carried by neurons in response to the whisker stimulation. Main results. We found that the behavioral state of the animal modulated the total amount of information conveyed by neurons and that the timing of individual spikes increased the information compared to the total count of spikes alone. However, the temporal information, i.e. information exclusively related to when the spikes occur, was not modulated by behavioral state. Significance. We conclude that information about somatosensory stimuli is modulated by the behavior of the animal and this modulation is mainly expressed in the spike count while the temporal information is more robust to changes in behavioral state.

  11. Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats.

    PubMed

    Nirujogi, Raja Sekhar; Wright, James D; Manda, Srikanth S; Zhong, Jun; Na, Chan Hyun; Meyerhoff, James; Benton, Bernard; Jabbour, Rabih; Willis, Kristen; Kim, Min-Sik; Pandey, Akhilesh; Sekowski, Jennifer W

    2015-01-01

    To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

  12. Diabetes alters myelin lipid profile in rat cerebral cortex: Protective effects of dihydroprogesterone.

    PubMed

    Cermenati, Gaia; Giatti, Silvia; Audano, Matteo; Pesaresi, Marzia; Spezzano, Roberto; Caruso, Donatella; Mitro, Nico; Melcangi, Roberto Cosimo

    2017-04-01

    Due to the emerging association of diabetes with several psychiatric and neurodegenerative events, the evaluation of the effects of this pathology on the brain function has now a high priority in biomedical research. In particular, the effects of diabetes on myelin compartment have been poorly taken into consideration. To this purpose, we performed a deep lipidomic analysis of cortical myelin in the streptozotocin-induced diabetic rat model. In male rats three months of diabetes induced an extensive alterations in levels of phosphatidylcholines and phosphatidylethanolamines (the main species present in myelin membranes), plasmalogens as well as phosphatidylinositols and phosphatidylserines. In addition, the levels of cholesterol and myelin basic protein were also decreased. Because these lipids exert important functional and structural roles in the myelin compartment, our data indicate that cerebral cortex myelin is severely compromised in diabetic status. Treatment for one-month with a metabolite of progesterone, dihydroprogesterone, restored the lipid and protein myelin profiles to the levels observed in non-diabetic animals. These data suggest the potential of therapeutic efficacy of DHP to restore myelin in the diabetic brain.

  13. Spike count, spike timing and temporal information in the cortex of awake, freely moving rats

    PubMed Central

    Scaglione, Alessandro; Foffani, Guglielmo; Moxon, Karen A.

    2014-01-01

    Objective Sensory processing of peripheral information is not stationary but is, in general, a dynamic process related to the behavioral state of the animal. Yet the link between the state of the behavior and the encoding properties of neurons is unclear. This report investigates the impact of the behavioral state on the encoding mechanisms used by cortical neurons for both detection and discrimination of somatosensory stimuli in awake, freely moving, rats. Approach Neuronal activity was recorded from the primary somatosensory cortex of five rats under two different behavioral states (quiet vs. whisking) while electrical stimulation of increasing stimulus strength was delivered to the mystacial pad. Information theoretical measures were then used to measure the contribution of different encoding mechanisms to the information carried by neurons in response to the whisker stimulation. Main Results We found that the behavioral state of the animal modulated the total amount of information conveyed by neurons and that the timing of individual spikes increased the information compared to the total count of spikes alone. However, the temporal information, i.e. information exclusively related to when the spikes occur, was not modulated by behavioral state. Significance We conclude that information about somatosensory stimuli is modulated by the behavior of the animal and this modulation is mainly expressed in the spike count while the temporal information is more robust to changes in behavioral state. PMID:25024291

  14. Na(+), K(+)-ATPase dysfunction causes cerebrovascular endothelial cell degeneration in rat prefrontal cortex slice cultures.

    PubMed

    Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Katsuki, Hiroshi

    2016-08-01

    Cerebrovascular endothelial cell dysfunction resulting in imbalance of cerebral blood flow contributes to the onset of psychiatric disorders such as depression, schizophrenia and bipolar disorder. Although decrease in Na(+), K(+)-ATPase activity has been reported in the patients with schizophrenia and bipolar disorder, the contribution of Na(+), K(+)-ATPase to endothelial cell dysfunction remains poorly understood. Here, by using rat neonatal prefrontal cortex slice cultures, we demonstrated that pharmacological inhibition of Na(+), K(+)-ATPase by ouabain induced endothelial cell injury. Treatment with ouabain significantly decreased immunoreactive area of rat endothelial cell antigen-1 (RECA-1), a marker of endothelial cells, in a time-dependent manner. Ouabain also decreased Bcl-2/Bax ratio and phosphorylation level of glycogen synthase kinase 3β (GSK3β) (Ser9), which were prevented by lithium carbonate. On the other hand, ouabain-induced endothelial cell injury was exacerbated by concomitant treatment with LY294002, an inhibitor of phosphoinositide 3- (PI3-) kinase. We also found that xestospongin C, an inhibitor of inositol triphosphate (IP3) receptor, but not SEA0400, an inhibitor of Na(+), Ca(2+) exchanger (NCX), protected endothelial cells from cytotoxicity of ouabain. These results suggest that cerebrovascular endothelial cell degeneration induced by Na(+), K(+)-ATPase inhibition resulting in Ca(2+) release from endoplasmic reticulum (ER) and activation of GSK3β signaling underlies pathogenesis of these psychiatric disorders.

  15. QUANTIFICATION OF SYNAPTIC DENSITY IN CORTICOSTRIATAL PROJECTIONS FROM RAT MEDIAL AGRANULAR CORTEX

    PubMed Central

    Reep, Roger L.; Wu, Jennifer H.; Cheatwood, Joseph L.; Corwin, James V.; Kartje, Gwendolyn L.; Mir, Anis

    2014-01-01

    Medial agranular cortex (AGm) has a prominent bilateral projection to the dorsocentral striatum (DCS). We wished to develop a normal baseline by which to assess neuronal plasticity in this corticostriatal system in rats with neglect resulting from a unilateral lesion in AGm, followed by treatment with agents that promote sprouting and functional recovery in other systems. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in DCS (the latter represent presynaptic profiles). Labeling density in contralateral DCS is approximately half that seen in ipsilateral DCS (this ratio is 0.50 for axons, 0.55 for varicosities). The ratio of varicosities is stable over a greater than seven-fold range of absolute densities. There is no consistent relationship between the absolute density of axons and axon varicosities; however, the ratio measures are strongly correlated. We conclude that changes in the contralateral/ipsilateral ratio of axon density after experimental treatments do reflect changes in synaptic density, but axon varicosities are likely to be the most sensitive anatomical parameter by which to assess plasticity at the light microscopic level. PMID:18691563

  16. Effects of sensory deprivation on columnar organization of neuronal circuits in the rat barrel cortex.

    PubMed

    Schierloh, Anja; Eder, Matthias; Zieglgänsberger, Walter; Dodt, Hans-Ulrich

    2004-08-01

    We examined whether sensory deprivation during formation of the cortical circuitry influences the pattern of intracortical single-cell connections in rat barrel cortex. Excitatory postsynaptic potentials (EPSPs) from layer 2/3 (L2/3) pyramidal neurons were recorded in vitro using patch-clamp techniques. In order to evoke EPSPs, presynaptic neurons were stimulated by photolytically applied glutamate, thus generating action potentials. Synaptic connections between the stimulated and the recorded neuron were identified by the occurrence of PSPs following photostimulation. Sensory deprivation changed the pattern of projections from L4 and L2/3 neurons to L2/3 pyramidal cells. In slices of non-deprived rats 86% of the total presynaptic neurons were located in the first and only 10% in the second barrel column. Deprivation changed these values to 67% and 26%, respectively. Therefore, the probability of presynaptic cells projecting to L2/3 neurons was shifted from adjacent to more remote barrel columns. These results indicate that deprivation of sensory input influences the pattern of intracortical connections.

  17. Intracerebroventricular administration of ouabain alters synaptic plasticity and dopamine release in rat medial prefrontal cortex.

    PubMed

    Sui, Li; Song, Xiao-Jin; Ren, Jie; Ju, Li-Hua; Wang, Yan

    2013-08-01

    Intracerebroventricular (ICV) administration of ouabain, a specific Na-K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 μl of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which did not be affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.

  18. Acute and chronic effects of nicotine on serotonin uptake in prefrontal cortex and hippocampus of rats.

    PubMed

    Awtry, Tammy L; Werling, Linda L

    2003-12-01

    We sought to investigate the effect of nicotine exposure (chronic and acute) on serotonin transporter (SERT) activity in two regions of the brain important for behavioral effects of nicotine. We first looked at the effects of chronic nicotine exposure (0.7 mg/kg nicotine, twice a day for 10 days) on [(3)H]5-HT uptake in prefrontal cortex (PFC) and hippocampus of rats. A significant increase in [(3)H]5-HT uptake was observed in synaptosomes prepared from both regions. To rule out the possibility that the increases were due to the last injection given, in a separate set of experiments a single injection of nicotine was administered the evening before sacrifice. No change in uptake occurred in either region, suggesting that the increases in uptake caused by nicotine was an effect of chronic exposure and not to an acute treatment. SERT binding studies, using prefrontocortical or hippocampal membrane preparations, revealed that chronic nicotine exposure significantly increased B(max) which correlated to an increase in SERT density. Lastly, we looked at the short-term effect of nicotine on [(3)H]5-HT uptake. Rats received a single nicotine injection 15-75 min before sacrifice. PFC synaptosomes displayed a time-dependent increase in uptake, whereas hippocampal synaptosomes showed an increase at only one time point.

  19. Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat

    PubMed Central

    Zhao, Tianyun; Li, Chuanxiang; Wei, Wei; Zhang, Haixing; Ma, Daqing; Song, Xingrong; Zhou, Libing

    2016-01-01

    Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings. PMID:27226073

  20. Moutan cortex extract exerts protective effects in a rat model of cardiac ischemia/reperfusion.

    PubMed

    Dan, Hong; Zhang, Liping; Qin, Xiaolin; Peng, Xiaohui; Wong, Mingyan; Tan, Xuan; Yu, Shanggong; Fang, Nianbai

    2016-03-01

    Moutan cortex (MC) is a traditional Chinese medicine with diverse biological effects. The present study was performed to investigate the effects of MC on myocardial ischemia/reperfusion (I/R) in rats and to explore its possible mechanisms. Sprague-Dawley rats were administered MC extract (1.98 g/kg, i.g.) for 14 days and underwent a subsequent open-chest procedure involving 30 min of myocardial ischemia and 60 min of reperfusion. The cardioprotective effect of MC was demonstrated by reduced infarct size and marked improvement in the histopathological examination. The increase in the activity of superoxide dismutase (SOD) and glutathione (GSH) as well as the reduction of malondialdehyde (MDA) indicated that MC effectively promoted the anti-oxidative defense system. Increased anti-oxidative defense was accompanied by decreased release of lactate dehydrogenase (LDH) and creatine kinase (CK). The reduction in TUNEL-positive myocytes demonstrated that MC decreased myocardial apoptosis. The mRNA expression of B cell leukemia-2 (Bcl-2) was upregulated by MC and the ratio of Bcl-2/Bcl-2-associated X protein (Bax) mRNA expression was increased. MC pretreatment decreased the mRNA expression of inducible nitric oxide synthase (iNOS). The data from this study suggest that MC exerted protective effects on acute myocardial I/R injury via anti-oxidative and anti-apoptotic activities.

  1. Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory

    PubMed Central

    Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F.T.

    2008-01-01

    Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP3-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP3 receptor (IP3R)-evoked calcium release results in SK channel-dependent hyperpolarization of prefrontal neurons. However, the effects of IP3R signaling on prefrontal function have not been investigated. The present findings demonstrate that blockade of IP3R or SK channels in the prefrontal cortex enhances WM performance in rats, suggesting that both arms of the PI cascade influence prefrontal cognitive function. PMID:18285467

  2. Molecular correlates of cortical network modulation by long-term sensory experience in the adult rat barrel cortex

    PubMed Central

    Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J.M.

    2014-01-01

    Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment up-regulates cortical expression of neuropeptide mRNAs and down-regulates immediate-early gene (IEG) mRNAs specifically in the barrel cortex, and not in other brain regions. The present data suggest a central role of neuropeptides in the fine-tuning of sensory cortical circuits by long-term experience. PMID:25171421

  3. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

    PubMed

    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.

  4. Effect of emotional stress on biogenic amine content in the sensorimotor cortex of rats with experimental intracerebral hemorrhage.

    PubMed

    Pertsov, S S; Ivannikova, N O; Krylin, V V

    2013-02-01

    Experiments on the model of an aggressive-conflict situation were designed to study the effect of emotional stress on biogenic amine content in the sensorimotor cortex of the right cerebral hemisphere in behaviorally active and passive rats with experimental hemorrhage in the left caudate nucleus of the brain. Prior exposure to stress in active and, particularly, in passive animals was shown to modify the type of neurochemical reactions in brain tissue during modeling of intracerebral hemorrhage. As differentiated from rats with experimental hemorrhagic stroke, passive specimens of this series were characterized by a slight increase in norepinephrine content and significant elevation of dopamine level in the sensorimotor cortex on day 3 of the study. An increase in dopamine content in brain tissue of stressed active rats was observed on days 1 and 3, which corresponded to the immediate and acute stages of the post-stroke period. Variations in serotonin content in the sensorimotor cortex of animals with post-stress intracerebral hemorrhage had the same dynamics, but were less pronounced than in non-stressed rats. Our results illustrate the specific involvement of brain biogenic amines in animals with various behavioral characteristics in the adaptive and compensatory processes, which occur during various stages of experimental intracerebral hemorrhage after stress exposure.

  5. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

    SciTech Connect

    Silva, J.E.; Matthews, P.S.

    1984-09-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.

  6. Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats.

    PubMed

    Yang, L-X; Jin, C-L; Zhu-Ge, Z-B; Wang, S; Wei, E-Q; Bruce, I C; Chen, Z

    2006-01-01

    Low-frequency stimulation of the kindling site interferes with the course of kindling epileptogenesis. The present study examined the effect of unilateral low-frequency stimulation of the central piriform cortex on seizure development induced by amygdaloid kindling in rats. The ipsilateral or contralateral central piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses at 1 Hz and 50-150 muA) immediately after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or contralateral central piriform cortex significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling. The marked suppression induced by low-frequency stimulation of the central piriform cortex on either side was predominantly due to the significant retardation of progression from stage 0 to stage 1 and stage 3 to stage 4 seizures. In addition, the suppressive effect of low-frequency stimulation did not disappear when the stimulation was stopped; it could persist for at least 10 days. These findings indicate that brain areas other than the kindling focus, such as the central piriform cortex on both sides, can also be used as reasonable targets for low-frequency stimulation to retard seizure development induced by amygdaloid kindling. Secondly, like the ipsilateral central piriform cortex, the contralateral central piriform cortex may also participate in the progression and secondary generalization of focal seizures. The study suggests that unilateral low-frequency stimulation of the central piriform cortex may have a significant antiepileptogenic effect, and may be helpful for exploring effective and long-lasting therapies for human temporal lobe epilepsy.

  7. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model.

    PubMed

    Luque, Niceto R; Garrido, Jesús A; Naveros, Francisco; Carrillo, Richard R; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range).

  8. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model

    PubMed Central

    Luque, Niceto R.; Garrido, Jesús A.; Naveros, Francisco; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range). PMID:26973504

  9. Distinct critical cerebellar subregions for components of verbal working memory

    PubMed Central

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2014-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum. PMID:22133495

  10. The physiological basis of therapies for cerebellar ataxias

    PubMed Central

    Mitoma, Hiroshi; Manto, Mario

    2016-01-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of ‘restorable stage’. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  11. Cerebellar mass as a location of acute lymphoblastic leukaemia.

    PubMed

    Desideri, Ilaria; Canovetti, Silvia; Pesaresi, Ilaria; Caniglia, Michele; Ciancia, Eugenio; Bartolozzi, Carlo; Puglioli, Michele; Cosottini, Mirco

    2014-09-01

    A 22-year-old man with acute lymphoblastic leukaemia was referred to our observation for headache, cervical pain and sopor. A computed tomography study revealed triventricular obstructive hydrocephalus due to a left cerebellar hyperdense mass impinging on the fourth ventricle. A magnetic resonance study demonstrated an area of hyperintensity on T2-weighted images, hypointensity on T1, restricted diffusivity and contrast enhancement involving the left hemispherical cerebellar cortex and the vermis and causing cerebellar herniation. After surgical excision of the lesion, histological examination revealed an infiltrate of lymphoblastic leukaemia with B cells. Leukaemic intracranial masses are rare. Our report describes a case presenting a cerebellar mass of leukaemic tissue characterized by high cellularity and low apparent diffusion coefficient value comparable to acute ischaemia. Therefore leukaemic intracranial mass has to be considered in the differential diagnosis of cerebellar masses.

  12. Maternal Iron Deficiency Worsens the Associative Learning Deficits and Hippocampal and Cerebellar Losses in a Rat Model of Fetal Alcohol Spectrum Disorders

    PubMed Central

    Huebner, Shane M.; Tran, Tuan D.; Rufer, Echoleah S.; Crump, Peter M.; Smith, Susan M.

    2015-01-01

    Background Gestational alcohol exposure causes lifelong physical and neurocognitive deficits collectively referred to as fetal alcohol spectrum disorders (FASDs). Micronutrient deficiencies are common in pregnancies of alcohol-abusing women. Here we show the most common micronutrient deficiency of pregnancy, iron deficiency without anemia, significantly worsens neurocognitive outcomes following perinatal alcohol exposure. Methods Pregnant rats were fed iron-deficient (ID) or iron-sufficient diets from gestational day 13 to postnatal day (PD) 7. Pups received alcohol (0, 3.5, 5.0 g/kg) from PD 4–9, targeting the brain growth spurt. At PD 32, learning was assessed using delay or trace eyeblink classical conditioning (ECC). Cerebellar interpositus nucleus (IPN) and hippocampal CA1 cellularity was quantified using unbiased stereology. Results Global ANOVA revealed that ID and alcohol separately and significantly reduced ECC learning with respect to amplitude (p’s ≤0.001) and CR percentage (p’s ≤0.001). Iron and alcohol interacted to reduce CR percentage in the trace ECC task (p = 0.013). Both ID and alcohol significantly reduced IPN (p’s <0.001) and CA1 cellularity (p’s < 0.005). CR amplitude correlated with IPN cellularity (Delay 0.871, Trace 0.703, p’s <0.001) and CA1 cellularity (Delay 0.792, Trace 0.846, p’s <0.001) across both tasks. The learning impairments persisted even through the offsprings’ iron status had normalized. Conclusion Supporting our previous work, gestational ID exacerbates the associative learning deficits in this rat model of FASD. This is strongly associated with cellular reductions within the ECC neurocircuitry. Significant learning impairments in FASD could be the consequence, in part, of pregnancies in which the mother was also iron-inadequate. PMID:26399568

  13. [The comparison of neuroprotective action of antibodies to glutamate and drug preparation semax in the focal ischemic damage of the brain prefrontal cortex of rats].

    PubMed

    Romanova, G A; Shakova, F M; Davydova, T V

    2012-01-01

    It was stated, that with bilateral photochemically induced thrombosis of the prefrontal cortex peptide semax and the AB-Glu by intranasal injection provoke pronounced neuroprotective and antiamnestic action. Intranasal injection semax (250 mkg/kg/daily during six postoperative days) and AB-Glu (250 mkg/kg in 1 hour after phototrombosis) demonstrate diminishing of cortex damage volume and relieve preservation and reproduction rat passive avoidance reflex, acquired before bilateral photochemically induced thrombosis of prefrontal cortex.

  14. [Analysis of Electroencephalogram Sample Entropy Measurement in Frontal Association Cortex Based on Heroin-induced Conditioned Place Preference in Rats].

    PubMed

    Huang, Lei; Pan, Qunwan; Zhu, Zaiman; Li, Jing; Gao, Chunfang; Li, Tian; Xu, Xiaoyan

    2015-04-01

    To explore the relationship between the drug-seeking behavior, motivation of conditioned place preference (CPP) rats and the frontal association cortex (FrA) electroencephalogram (EEG) sample entropy, we in this paper present our studies on the FrA EEG sample entropy of control group rats and CPP group rats, respectively. We invested different behavior in four situations of the rat activities, i. e. rats were staying in black chamber of videoed boxes, those staying in white chamber of videoed boxes, those shuttling between black-white chambers and those shuttling between white-black chambers. The experimental results showed that, compared with the control group rats, the FrA EEG sample entropy of CPP rats staying in black chamber of video box and shuttling between white-black chambers had no significant difference. However, sample entropy is significantly smaller (P < 0.01) when heroin-induced group rats stayed in white chamber of video box and shuttled between black-white chambers. Consequently, the drug-seeking behavior and motivation of CPP rats correlated closely with the EEG sample entropy changes.

  15. Pulsed infrared light alters neural activity in rat somatosensory cortex in vivo

    PubMed Central

    Cayce, Jonathan M.; Friedman, Robert M.; Jansen, E. Duco; Mahavaden-Jansen, Anita; Roe, Anna W.

    2011-01-01

    Pulsed infrared light has shown promise as an alternative to electrical stimulation in applications where contact free or high spatial precision stimulation are desired. Infrared neural stimulation (INS) is well characterized in the peripheral nervous system; however, to date, research has been limited in the central nervous system. In this study, pulsed infrared light (λ=1.875 μm, pulse width=250 μs, radiant exposure=0.01–0.55 J/cm2, fiber size=400 μm, repetition rate=50–200 Hz) was used to stimulate the somatosensory cortex of anesthetized rats, and its efficacy was assessed using intrinsic optical imaging and electrophysiology techniques. INS was found to evoke an intrinsic response of similar magnitude to that evoked by tactile stimulation (0.3–0.4% change in intrinsic signal magnitude). A maximum deflection in the intrinsic signal was measured to range from 0.05% to 0.4% in response to INS, and the activated region of cortex measured approximately 2 mm in diameter. The intrinsic signal magnitude increased with faster laser repetition rates and increasing radiant exposures. Single unit recordings indicated a statistically significant decrease in neuronal firing that was observed at the onset of INS stimulation (0.5 s stimulus) and continued up to 1 s after stimulation onset. The pattern of neuronal firing differed from that observed during tactile stimulation, potentially due to a different spatial integration field of the pulsed infrared light compared to tactile stimulation. The results demonstrate that INS can be used safely and effectively to manipulate neuronal firing. PMID:21513806

  16. Organization of anterior cingulate and frontal cortical projections to the retrosplenial cortex in the rat.

    PubMed

    Shibata, Hideshi; Naito, Jumpei

    2008-01-01

    The retrosplenial cortex (areas 29a-d), which plays an important role in spatial memory and navigation, is known to provide massive projections to frontal association and motor cortices, which are also essential for spatial behavior. The reciprocal projections originating from these frontal cortices to areas 29a-d, however, have been analyzed to only a limited extent. Here, we report an analysis of the anatomical organization of projections from anterior cingulate area 24 and motor and prefrontal cortices to areas 29a-d in the rat, using the axonal transport of cholera toxin B subunit and biotinylated dextran amine. Area 29a receives projections from rostral area 24a, area 24b, the ventral orbital area, and the caudal secondary motor area. Rostral area 29b receives projections from caudal area 24a, whereas caudal area 29b receives projections from rostral area 24a. Area 29b also receives projections from area 24b and the ventral orbital area. Areas 29c and 29d receive projections from areas 24a and 24b and the secondary motor area in a topographic manner such that the rostrocaudal axis of areas 29c and 29d corresponds to the caudorostral axis of areas 24a and 24b and the secondary motor area. Rostral areas 29c and 29d also receive projections from the caudal primary motor area, and area 29d receives projections from the ventral, lateral, and medial orbital areas. These differential frontal cortical projections to each area of the retrosplenial cortex suggest that each area may contribute to different aspects of retrosplenial cortical function such as spatial memory and behavior.

  17. Optical intrinsic signals in rat primary somatosensory cortex during non-noxious and noxious elecrical stimulation of the sciatic nerve

    NASA Astrophysics Data System (ADS)

    Luo, Weihua; Li, Pengcheng; Chen, Shangbin; Luo, Qingming

    2003-12-01

    Optical imaging method was applied into observing the temporal-spatial characteristic of rat primary somatosensory cortex during graded electrical stimulation of the sciatic nerve (5hz,duration of 2s,0.5ms puls,1x,10x and 20x muscle twitch threshold). We found that the temporal and spatial properties of hindlimb somatosensory cortex were modulated by graded intensity electrical stimulation of the sciatic nerve. The magnitude and time course were larger and longer with the intensity raising. And the spatial extent was wider at 20x stimulus than the other two kinds of stimulus. Therefore, our optical imaging was based on 570nm, which only reflect the changes of blood volume. Then our future study will reveal more information of pain modulation in primary somatosensory cortex.

  18. The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

    PubMed Central

    Burroughs, Amelia; Wise, Andrew K.; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y.; Lang, Eric J.

    2016-01-01

    Key points Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes.Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets.The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear.We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number.This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Abstract Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake

  19. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and