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Inhibitory Circuits (inhibitory + circuit)

Distribution by Scientific Domains

Life Sciences	86%
Medical Sciences	13%

Selected Abstracts

Pregabalin Exerts Oppositional Effects on Different Inhibitory Circuits in Human Motor Cortex: A Double-blind, Placebo-controlled Transcranial Magnetic Stimulation Study

EPILEPSIA, Issue 5 2006
Nicolas Lang
Summary:,Purpose: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). Methods: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. Results: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 ± 7% of unconditioned response) compared with placebo (60 ± 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 ± 4% of unconditioned response) compared with placebo (45 ± 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 ± 8 ms or 145 ± 8 ms after placebo to 162 ± 7 ms or 161 ± 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. Conclusions: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest ,-aminobutyric acid (GABA)B -receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the ,(2)-, subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine. [source]

Cortical inhibitory circuits in eye-movement generation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003
Peter H. Schiller
Abstract The role inhibitory circuits play in target selection with saccadic eye movements was examined in area V1, the frontal eye fields (FEF) and the lateral intraparietal sulcus (LIP) of the Rhesus Macaque monkey by making local infusions of the GABA agonist muscimol and antagonist bicuculline. In V1, both agents greatly interfered with target selection and visual discrimination of stimuli placed into the receptive field of the affected neurons. In the FEF, bicuculline facilitated target selection without affecting visual discrimination and generated many spontaneous saccades. Muscimol in the FEF interfered with saccadic eye-movement generation. In the LIP, bicuculline was ineffective and muscimol had only a small effect. These findings suggest that in the FEF GABAergic inhibitory circuits play a central role in eye-movement generation whereas in V1 these circuits are essential for visual analysis. Inhibitory circuits in the LIP do not appear to play a central role in target selection and in visual discrimination. [source]

Co-regulation of ocular dominance plasticity and NMDA receptor subunit expression in glutamic acid decarboxylase-65 knock-out mice

THE JOURNAL OF PHYSIOLOGY, Issue 12 2009
Patrick O. Kanold
Experience can shape cortical circuits, especially during critical periods for plasticity. In visual cortex, imbalance of activity from the two eyes during the critical period shifts ocular dominance (OD) towards the more active eye. Inhibitory circuits are crucial in this process: OD plasticity is absent in GAD65KO mice that show diminished inhibition. This defect can be rescued by application of benzodiazepines, which increase GABAergic signalling. However, it is unknown how such changes in inhibition might disrupt and then restore OD plasticity. Since NMDA dependent synaptic plasticity mechanisms are also known to contribute to OD plasticity, we investigated whether NMDA receptor levels and function are also altered in GAD65KO. There are reduced NR2A levels and slower NMDA currents in visual cortex of GAD65KO mice. Application of benzodiazepines, which rescues OD plasticity, also increases NR2A levels. Thus it appears as if OD plasticity can be restored by adding a critical amount of excitatory transmission through NR2A-containing NMDA receptors. Together, these observations can unify competing ideas of how OD plasticity is regulated: changes in either inhibition or excitation would engage homeostatic mechanisms that converge to regulate NMDA receptors, thereby enabling plasticity mechanisms and also ensuring circuit stability. [source]

Electrical and chemical synapses between relay neurons in developing thalamus

THE JOURNAL OF PHYSIOLOGY, Issue 13 2010
Seung-Chan Lee
Gap junction-mediated electrical synapses interconnect diverse types of neurons in the mammalian brain, and they may play important roles in the synchronization and development of neural circuits. Thalamic relay neurons are the major source of input to neocortex. Electrical synapses have not been directly observed between relay neurons in either developing or adult animals. We tested for electrical synapses by recording from pairs of relay neurons in acute slices of developing ventrobasal nucleus (VBN) of the thalamus from rats and mice. Electrical synapses were common between VBN relay neurons during the first postnatal week, and then declined sharply during the second week. Electrical coupling was reduced among cells of connexin36 (Cx36) knockout mice; however, some neuron pairs remained coupled. This implies that electrical synapses between the majority of coupled VBN neurons require Cx36 but that other gap junction proteins also contribute. The anatomical distribution of a ,-galactosidase reporter indicated that Cx36 was expressed in some VBN neurons during the first postnatal week and sharply declined over the second week, consistent with our physiological results. VBN relay neurons also communicated via chemical synapses. Rare pairs of relay neurons excited one another monosynaptically. Much more commonly, spikes in one relay neuron evoked disynaptic inhibition (via the thalamic reticular nucleus) in the same or a neighbouring relay neuron. Disynaptic inhibition between VBN cells emerged as electrical coupling was decreasing, during the second postnatal week. Our results demonstrate that thalamic relay neurons communicate primarily via electrical synapses during early postnatal development, and then lose their electrical coupling as a chemical synapse-mediated inhibitory circuit matures. [source]

Roles of distinct glutamate receptors in induction of anti-Hebbian long-term potentiation

THE JOURNAL OF PHYSIOLOGY, Issue 6 2008
Dimitri M. Kullmann
Many glutamatergic synapses on interneurons involved in feedback inhibition in the CA1 region of the hippocampus exhibit an unusual form of long-term potentiation (LTP) that is induced only if presynaptic glutamate release occurs when the postsynaptic membrane potential is relatively hyperpolarized. We have named this phenomenon ,anti-Hebbian' LTP because it is prevented by postsynaptic depolarization during afferent activity, and hence its induction requirements are opposite to those of Hebbian NMDA receptor-dependent LTP. This symposium report addresses the roles of distinct glutamate receptors in the induction of anti-Hebbian LTP. Inwardly rectifying Ca2+ -permeable AMPA receptors mediate fast glutamatergic signalling at synapses that exhibit this form of LTP, and they are highly likely to mediate the instructive signal that triggers the cascade leading to synapse strengthening. NMDA receptors, on the other hand, play no role, nor do they contribute substantially to synaptic transmission at synapses that exhibit anti-Hebbian LTP. Both kainate and group I metabotropic glutamate receptors are abundant in at least some interneurons in the feedback inhibitory circuit. Delineating the roles of kainate receptors has been hampered by sub-optimal pharmacological tools. As for group I metabotropic glutamate receptors, their role in anti-Hebbian LTP is permissive at the very least in some interneuron types, although an instructive role has been suggested in other forms of activity-dependent plasticity. [source]

Changes in presumed motor cortical activity during fatiguing muscle contraction in humans

ACTA PHYSIOLOGICA, Issue 3 2010
T. Seifert
Abstract Aim:, Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles. Methods:, During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus. Results:, During the first 2 min of the fatiguing muscle contraction the suppression was 10 ± 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 ± 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity. Conclusion:, Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output. [source]

Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic pain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010
Yasmina B. Martin
Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source]

Enhanced synaptic excitation,inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsy

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007
F. Stief
Abstract A common feature of all epileptic syndromes is the repetitive occurrence of pathological patterns of synchronous neuronal activity, usually combined with increased neuronal discharge rates. Inhibitory interneurons of the hippocampal formation control both neuronal synchronization as well as the global level of activity and are therefore of crucial importance for epilepsy. Recent evidence suggests that changes in synaptic inhibition during temporal lobe epilepsy are rather specific, resulting from selective death or alteration of interneurons in specific hippocampal layers. Hence, epilepsy-induced changes have to be analysed separately for different types of interneurons. Here, we focused on GABAergic neurons located at the border between stratum radiatum and stratum lacunosum-moleculare of hippocampal area CA1 (SRL interneurons), which are included in feedforward inhibitory circuits. In chronically epileptic rats at 6,8 months after pilocarpine-induced status epilepticus, frequencies of spontaneous and miniature inhibitory postsynaptic currents were reduced, yielding an almost three-fold increase in excitation,inhibition ratio. Consistently, action potential frequency of SRL interneurons was about two-fold enhanced. Morphological alterations of the interneurons indicate that these functional changes were accompanied by remodelling of the local network, probably resulting in a loss of functional inhibitory synapses without conceivable cell death. Our data indicate a strong increase in activity of interneurons in dendritic layers of the chronically epileptic CA1 region. This alteration may enhance feedforward inhibition and rhythmogenesis and , together with specific changes in other interneurons , contribute to seizure susceptibility and pathological synchronization. [source]

Cortical inhibitory circuits in eye-movement generation

Mu opioid receptors are in discrete hippocampal interneuron subpopulations

HIPPOCAMPUS, Issue 2 2002
Carrie T. Drake
Abstract In the rat hippocampal formation, application of mu opioid receptor (MOR) agonists disinhibits principal cells, promoting excitation-dependent processes such as epileptogenesis and long-term potentiation. However, the precise location of MORs in particular inhibitory circuits, has not been determined, and the roles of MORs in endogenous functioning are unclear. To address these issues, the distribution of MOR-like immunoreactivity (-li) was examined in several populations of inhibitory hippocampal neurons in the CA1 region using light and electron microscopy. We found that MOR-li was present in many parvalbumin-containing basket cells, but absent from cholecystokinin-labeled basket cells. MOR-li was also commonly in interneurons containing somatostatin-li or neuropeptide Y-li that resembled the "oriens,lacunosum-moleculare" (O-LM) interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in some vasoactive intestinal peptide- or calretinin-containing profiles resembling interneurons that primarily innervate other interneurons. These findings indicate that MOR-containing neurons form a neurochemically and functionally heterogeneous subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons that are specialized to inhibit pyramidal cells, and are on a limited number of interneurons that target other interneurons. Moreover, the distribution of MORs to different neuronal types in several laminae, some relatively far from endogenous opioids, suggests normal functional roles that are different from the actions seen with exogenous agonists such as morphine. Hippocampus 2002;12:119,136. © 2002 Wiley-Liss, Inc. [source]

Developmental pattern of synapsin I expression in mouse somatosensory cortex

JOURNAL OF NEUROCHEMISTRY, Issue 2003
M. Liguz-Lecznar
Synapsin I is a member of a synapsin family which are phosphoproteins associated with synaptic vesicles. It is thought to be involved in neuronal development and plasticity. We have shown the existence of two distinct patterns of synapsin I immunostaining in adult mice primary somatosensory cortex (SI). The first consisted of small, dispersed immunoreactive puncta in neuropil. The second is confined to the perikarya and proximal dendrites of the specific class of neurons present in layers IV and VI of SI, probably reflecting the expression of a novel isoform of synapsin I. The aim of this study was to examine the developmental pattern of synapsin I expression in mouse SI cortex. Using immunocytochemistry and Western blot analysis we found that this unique pattern of synapsin I expression in SI appeared between the 2nd and 3rd postnatal week and probably coincides with the increase in the number of synaptic contacts and the development of inhibitory circuits in SI. Acknowledgement: Supported by KBN grant no. 3P04C 008 22. [source]

Quantitative morphology and postsynaptic targets of thalamocortical axons in critical period and adult ferret visual cortex

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2005
Alev Erisir
Abstract Thalamocortical axons segregate into ocular dominance columns several weeks before the onset of critical period plasticity in ferret visual cortex, a stage characterized by anatomical changes in thalamic input as a consequence of abnormal visual stimulation. In search of possible anatomical correlates of this plasticity, we examined, at electron microscope resolution, the morphology and the synapsing and target selection properties of thalamic axons in ferret visual cortex during and after the critical period. Adult thalamocortical terminals visualized by anterograde tract-tracing display significantly larger cross-section areas than terminals at postnatal day (P) 35, P40, and P49 critical period ages. They are also significantly larger than nonthalamocortical terminals, which attain an adult-like size distribution by P40. The synaptic zones of adult thalamocortical terminals are significantly larger than those of critical period terminals. Perforated and invaginated synapses are encountered frequently on thalamic axons in both adulthood and the P40,49 age group. This result contradicts the view that synaptic perforations and spinules are indicative of a capacity for plasticity. It also suggests that at least some morphological features of thalamic terminals attain maturity on a developmental schedule that is independent of critical period plasticity. Connectivity properties of labeled axons, however, suggest an active role for thalamocortical axons in the critical period. In P40, P49, and adult brains, 23%, 17%, and 9%, respectively, of all thalamocortical synapses contact GABAergic interneurons, suggesting that thalamic input is more strongly involved in driving inhibitory circuits in young ages. Furthermore, thalamocortical axons in P35,49 brains form about 60% more synapses per axon length than in adult brains, suggesting that stabilization of thalamic synapses at the end of the critical period may be accompanied by a reduction of synaptic contacts, as well as a reorganization of postsynaptic circuit selectivity. J. Comp. Neurol. 485:11,31, 2005. © 2005 Wiley-Liss, Inc. [source]

Active properties of motoneurone dendrites: diffuse descending neuromodulation, focused local inhibition

THE JOURNAL OF PHYSIOLOGY, Issue 5 2008
C. J. Heckman
The dendrites of spinal motoneurones are highly active, generating a strong persistent inward current (PIC) that has an enormous impact on processing of synaptic input. The PIC is subject to regulation by descending neuromodulatory systems releasing the monoamines serotonin and noradrenaline. At high monoaminergic drive levels, the PIC dominates synaptic integration, generating an intrinsic dendritic current that is as much as 5-fold larger than the current entering via synapses. Without the PIC, motoneurone excitability is very low. Presumably, this descending control of the synaptic integration via the PIC is used to adjust the excitability (gain) of motoneurones for different motor tasks. A problem with this gain control is that monoaminergic input to the cord is very diffuse, affecting many motor pools simultaneously, probably including both agonists and antagonists. The PIC is, however, exquisitely sensitive to the reciprocal inhibition mediated by length sensitive muscle spindle Ia afferents and Ia interneurones. Reciprocal inhibition is tightly focused, shared only between strict mechanical antagonists, and thus can act to ,sculpt' specific movement patterns out of a background of diffuse neuromodulation. Thus it is likely that motoneurone gain is set by the interaction between diffuse descending neuromodulation and specific and focused local synaptic inhibitory circuits. [source]

Cortical disinhibition in diabetic patients with neuropathic pain

ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009
N. Turgut
Objectives,,, Motor cortex disinhibition has a role in the mechanism of neuropathic pain. The duration of the cortical silent period (CSP) is used as a measure of excitability in cortical inhibitory circuits. We investigated cortical disinhibition in diabetic patients with and without neuropathic pain. Materials and methods,,, We studied diabetic patients with (n = 20) and without (n = 50) neuropathic pain, and control subjects (n = 30). Transcranial magnetic stimulation (TMS) was performed on the right hemisphere at rest, and surface electromyography was recorded from the left first dorsal interosseous muscle for evaluation of motor evoked potential (MEP) latency and amplitude. CSP was recorded from the left FDI, and TMS was then delivered while the subject was performing a voluntary contraction. Results,,, We showed a low resting motor threshold, a short CSP duration, and a low CSP duration/MEP amplitude ratio in patients with neuropathic pain (P < 0.0001, P < 0.0001, P < 0.0001). Conclusions,,, Our findings demonstrate that diabetic patients with neuropathic pain have a cortical disinhibition. [source]