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Inhibitory Synaptic Transmission (inhibitory + synaptic_transmission)
Selected AbstractsVasopressin Preferentially Depresses Excitatory Over Inhibitory Synaptic Transmission in the Rat Supraoptic Nucleus In VitroJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2000Kombian1 Endogenous arginine-vasopressin (AVP) in the supraoptic nucleus is known to decrease the firing rate of some supraoptic nucleus neurones. To determine a possible mechanism by which this locally released AVP produces this change in neuronal excitability, we investigated the effects of AVP on evoked excitatory (e.p.s.c.) and inhibitory post-synaptic (i.p.s.c.) responses recorded in magnocellular neurones in a hypothalamic slice preparation, using the perforated-patch recording technique. Our data show that AVP produces a dose-dependent decrease in the evoked e.p.s.c. in about 80% of magnocellular neurones tested with an estimated EC50 of about 0.9 ,M. The maximum decrease in e.p.s.c. amplitude was about 31% of control and was obtained with an AVP concentration of 2 ,M. The AVP-induced synaptic depression was blocked by Manning Compound (MC), a non-selective antagonist of oxytocin (OXT) and vasopressin (AVP) receptors, but not by a selective OXT receptor antagonist. It was not mimicked by desmopressin (ddAVP), a V2-receptor subtype agonist. By contrast, AVP used at the same concentration (2 ,M), had no global effect on pharmacologically isolated i.p.s.c.s in the majority of magnocellular neurones tested. These results show that AVP acts in the supraoptic nucleus to reduce excitatory synaptic transmission to magnocellular neurones by activating a non-OXT receptor, presumably the V1 receptor subtype. [source] The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cordACTA PHYSIOLOGICA, Issue 2 2009H. Nishimaru Abstract Neuronal circuits generating the basic coordinated limb movements during walking of terrestrial mammals are localized in the spinal cord. In these neuronal circuits, called central pattern generators (CPGs), inhibitory synaptic transmission plays a crucial part. Inhibitory synaptic transmission mediated by glycine and GABA is thought to be essential in coordinated activation of muscles during locomotion, in particular, controlling temporal and spatial activation patterns of muscles of each joint of each limb on the left and right side of the body. Inhibition is involved in other aspects of locomotion such as control of speed and stability of the rhythm. However, the precise roles of neurotransmitters and their receptors mediating inhibitory synaptic transmission in mammalian spinal CPGs remain unclear. Moreover, many of the inhibitory interneurones essential for output pattern of the CPG are yet to be identified. In this review, recent advances on these issues, mainly from studies in the developing rodent spinal cord utilizing electrophysiology, molecular and genetic approaches are discussed. [source] Genetic and pharmacological studies of GluR5 modulation of inhibitory synaptic transmission in the anterior cingulate cortex of adult miceDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2007Long-Jun Wu Abstract In the anterior cingulate cortex (ACC), GluR5-containing kainate receptor mediated the small portion of excitatory postsynaptic current. However, little is known about its role in modulation of neurotransmitter release in this brain region. In the present study, we address this question by using selective GluR5 agonist and antagonist, as well as GluR5,/, mice. Our results showed that activation of GluR5 induced action potential-dependent GABA release, which is also required for the activation of voltage-dependent calcium channel and Ca2+ influx. The effect of GluR5 activation is selective to the GABAergic, but not glutamatergic synaptic transmission. Endogenous activation of GluR5 also enhanced GABA release to ACC pyramidal neurons and the corresponding postsynaptic tonic GABA current. Our results suggest the somatodendritic, but not presynaptic GluR5, in modulation of GABA release. The endogenous GluR5 activation and the subsequent tonic GABA current may play an inhibitory role in ACC-related brain functions. © 2006 Wiley Periodicals, Inc. Develop Neurobiol 67: 146,157, 2007. [source] Epileptiform synchronization in the cingulate cortexEPILEPSIA, Issue 3 2009Gabriella Panuccio Summary Purpose:, The anterior cingulate cortex (ACC),which plays a role in pain, emotions and behavior,can generate epileptic seizures. To date, little is known on the neuronal mechanisms leading to epileptiform synchronization in this structure. Therefore, we investigated the role of excitatory and inhibitory synaptic transmission in epileptiform activity in this cortical area. In addition, since the ACC presents with a high density of opioid receptors, we studied the effect of opioid agonism on epileptiform synchronization in this brain region. Methods:, We used field and intracellular recordings in conjunction with pharmacological manipulations to characterize the epileptiform activity generated by the rat ACC in a brain slice preparation. Results:, Bath-application of the convulsant 4-aminopyridine (4AP, 50 ,M) induced both brief and prolonged periods of epileptiform synchronization resembling interictal- and ictal-like discharges, respectively. Interictal events could occur more frequently before the onset of ictal activity that was contributed by N -methyl- d -aspartate (NMDA) receptors. Mu-opioid receptor activation abolished 4AP-induced ictal events and markedly reduced the occurrence of the pharmacologically isolated GABAergic synchronous potentials. Ictal discharges were replaced by interictal events during GABAergic antagonism; this GABA-independent activity was influenced by subsequent mu-opioid agonist application. Conclusions:, Our results indicate that both glutamatergic and GABAergic signaling contribute to epileptiform synchronization leading to the generation of electrographic ictal events in the ACC. In addition, mu-opioid receptors appear to modulate both excitatory and inhibitory mechanisms, thus influencing epileptiform synchronization in the ACC. [source] Developmental changes in the BDNF-induced modulation of inhibitory synaptic transmission in the Kölliker,Fuse nucleus of ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Miriam Kron Abstract The Kölliker,Fuse nucleus (KF), part of the pontine respiratory group, is involved in the control of respiratory phase duration, and receives both excitatory and inhibitory afferent input from various other brain regions. There is evidence for developmental changes in the modulation of excitatory inputs to the KF by the neurotrophin brain-derived neurotrophic factor (BDNF). In the present study we investigated if BDNF exerts developmental effects on inhibitory synaptic transmission in the KF. Recordings of inhibitory postsynaptic currents (IPSCs) in KF neurons in a pontine slice preparation revealed general developmental changes. Recording of spontaneous and evoked IPSCs (sIPSCs, eIPSCS) revealed that neonatally the ,-aminobutyric acid (GABA)ergic fraction of IPSCs was predominant, while in later developmental stages glycinergic neurotransmission significantly increased. Bath-application of BDNF significantly reduced sIPSC frequency in all developmental stages, while BDNF-mediated modulation on eIPSCs showed developmental differences. The eIPSCs mean amplitude was uniformly and significantly reduced following BDNF application only in neurons from rats younger than postnatal day 10. At later postnatal stages the response pattern became heterogeneous, and both augmentations and reductions of eIPSC amplitudes occurred. All BDNF effects on eIPSCs and sIPSCs were reversed with the tyrosine kinase receptor-B inhibitor K252a. We conclude that developmental changes in inhibitory neurotransmission, including the BDNF-mediated modulation of eIPSCs, relate to the postnatal maturation of the KF. The changes in BDNF-mediated modulation of IPSCs in the KF may have strong implications for developmental changes in synaptic plasticity and the adaptation of the breathing pattern to afferent inputs. [source] Depression of retinogeniculate synaptic transmission by presynaptic D2 -like dopamine receptors in rat lateral geniculate nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006G. Govindaiah Abstract Extraretinal projections onto neurons in the dorsal lateral geniculate nucleus (dLGN) play an important role in modifying sensory information as it is relayed from the visual thalamus to neocortex. The dLGN receives dopaminergic innervation from the ventral tegmental area; however, the role of dopamine in synaptic transmission in dLGN has not been explored. In the present study, whole cell recordings were obtained to examine the actions of dopamine on glutamatergic synaptic transmission. Dopamine (2,100 µm) strongly suppressed excitatory synaptic transmission in dLGN relay neurons that was evoked by optic tract stimulation and mediated by both N -methyl- d -aspartate and non -N -methyl- d -aspartate glutamate receptors. In contrast, dopamine did not alter inhibitory synaptic transmission arising from either dLGN interneurons or thalamic reticular nucleus neurons. The suppressive action of dopamine on excitatory synaptic transmission was mimicked by the D2 -like dopamine receptor agonist bromocriptine (2,25 µm) but not by the D1 -like receptor agonist SKF38393 (10,25 µm). In addition, the dopamine-mediated suppression was antagonized by the D2 -like receptor antagonist sulpiride (10,20 µm) but not by the D1 -like receptor antagonist SCH23390 (5,25 µm). The dopamine-mediated decrease in evoked excitatory postsynaptic current amplitude was accompanied by an increase in the magnitude of paired-pulse depression. Furthermore, dopamine also reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. Taken together, these data suggest that dopamine may act presynaptically to regulate the release of glutamate at the retinogeniculate synapse and modify transmission of visual information in the dLGN. [source] A new class of neurotoxin from wasp venom slows inactivation of sodium currentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Yoshinori Sahara Abstract The effects of ,-pompilidotoxin (,-PMTX), a new neurotoxin isolated from the venom of a solitary wasp, were studied on the neuromuscular synapses in lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired intracellular recordings from the presynaptic axon terminals and the innervating lobster leg muscles revealed that ,-PMTX induced long bursts of action potentials in the presynaptic axon, which resulted in facilitated excitatory and inhibitory synaptic transmission. The action of ,-PMTX was distinct from that of other known facilitatory presynaptic toxins, including sea anemone toxins and ,-scorpion toxins, which modify the fast inactivation of Na+ current. We further characterized the action of ,-PMTX on Na+ channels by whole-cell recordings from rat trigeminal neurons. We found that ,-PMTX slowed the Na+ channels inactivation process without changing the peak current,voltage relationship or the activation time course of tetrodotoxin (TTX)-sensitive Na+ currents, and that ,-PMTX had voltage-dependent effects on the rate of recovery from Na+ current inactivation and deactivating tail currents. The results suggest that ,-PMTX slows or blocks conformational changes required for fast inactivation of the Na+ channels on the extracellular surface. The simple structure of ,-PMTX, consisting of 13 amino acids, would be advantageous for understanding the functional architecture of Na+ channel protein. [source] Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptorsHIPPOCAMPUS, Issue 8 2009Changqing Xu Abstract Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24,26 months old) and young (2,4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. © 2009 Wiley-Liss, Inc. [source] Bi-directional modulation of fast inhibitory synaptic transmission by leptinJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Natasha Solovyova Abstract The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABAA receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABAA receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABAA receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability. [source] Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatumJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Matthew T. Whittaker Abstract Neuromodulators that alter the balance between lower-frequency glutamate-mediated excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABAA receptor mediated synaptic transmission. The enzymes necessary for PS synthesis and degradation are found in brain tissue of several species including human and rat, and up to 5 nM PS has been detected in extracts of postmortem human brain. Here, we ask whether PS could modulate transmitter release from nerve terminals located in the striatum. Superfusion of a preparation of striatal nerve terminals comprised of mixed synaptosomes and synaptoneurosomes with brief-duration (2 min) pulses of 25 nM PS demonstrates that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that it specifically affects the transmitter release mechanism. The PS-induced [3H]DA release occurs via an NMDA receptor (NMDAR) dependent mechanism as it is blocked by D-2-amino-5-phosphonovaleric acid. PS modulates DA release with very high potency, significantly increasing [3H]DA release at PS concentrations as low as 25 pM. This first report of a selective direct enhancement of synaptosomal dopamine release by PS at picomolar concentrations via an NMDAR dependent mechanism raises the possibility that dopaminergic axon terminals may be a site of action for this neurosteroid. [source] GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneuronsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003Saobo Lei Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABAB receptor-mediated responses at both synapse types. Postsynaptic GABAB receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (P30) suggesting developmental regulation. In young animals, the GABAB receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd2+, implicating presynaptic voltage-gated Ca2+ channels as a target for baclofen modulation. In contrast, although Cd2+ prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca2+ channels contributed equally to GABAB receptor-mediated inhibition of EPSCs, more P/Q-type Ca2+ channels were involved in GABAB receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABAB receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types. [source] In vivo optical recordings of synaptic transmission and intracellular Ca2+ and Cl, in the superior colliculus of fetal ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Yoshiyuki Sakata Abstract Although the N -methyl- d -aspartate (NMDA) receptor is known to play a crucial role in activity-dependent remodeling of synaptic connections in the fetal superior colliculus (SC), its contribution to the electrical activity of fetal SC neurons has not been determined. Furthermore, whether ,-aminobutyric acid (GABA)-mediated inhibition occurs either as early as prenatal periods or only after eye opening has been controversial. We therefore performed optical recordings using voltage-, Ca2+ - and Cl, -sensitive fluorescent dyes to analyse synaptic transmission and changes in intracellular Ca2+ and Cl, in the SC of fetal rats that were still connected with the dams by the umbilical cord. Excitatory and inhibitory responses were evoked by focal SC stimulation. The excitatory synaptic responses are composed of early and late components. The early component was mediated by both non-NMDA and NMDA receptors, whereas the late component occurred mainly via NMDA receptors. Train pulse stimulation at higher currents was required for induction of the inhibition, which was antagonized by bicuculline, and blocking of the GABA-mediated inhibition by bicuculline uncovered masked excitatory synaptic responses. Focal SC stimulation induced increases in [Cl,]i and [Ca2+]i that were mediated by GABA-A receptors and mainly by NMDA receptors, respectively. GABA antagonists augmented SC-induced increases in [Ca2+]i. These results indicate that, in the fetal SC, excitatory and inhibitory synaptic transmissions occur before birth, that the NMDA receptor is a major contributor to excitatory synaptic transmission and increased [Ca2+]i, and that the GABA-A receptor is already functioning to inhibit excitatory neurotransmission. [source] | |||||||||||||