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Postsynaptic Currents (postsynaptic + current)
Kinds of Postsynaptic Currents Selected AbstractsPre- and postsynaptic contributions of voltage-dependent Ca2+ channels to nociceptive transmission in rat spinal lamina I neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004B. Heinke Abstract Activation of voltage-dependent Ca2+ channels (VDCCs) is critical for neurotransmitter release, neuronal excitability and postsynaptic Ca2+ signalling. Antagonists of VDCCs can be antinociceptive in different animal pain models. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the processing of pain-related information, but the role of VDCCs to the activity-dependent Ca2+ increase in lamina I neurons and to the synaptic transmission between nociceptive afferents and second order neurons in lamina I is not known. This has now been investigated in a lumbar spinal cord slice preparation from young Sprague,Dawley rats. Microfluorometric Ca2+ measurements with fura-2 have been used to analyse the Ca2+ increase in lamina I neurons after depolarization of the cells, resulting in a distinct and transient increase of the cytosolic Ca2+ concentration. This Ca2+ peak was reduced by the T-type channel blocker, Ni2+, by the L-type channel blockers, nifedipine and verapamil, and by the N-type channel blocker, ,-conotoxin GVIA. The P/Q-type channel antagonist, ,-agatoxin TK, had no effect on postsynaptic [Ca2+]i. The NMDA receptor channel blocker D-AP5 reduced the Ca2+ peak, whereas the AMPA receptor channel blocker CNQX had no effect. Postsynaptic currents, monosynaptically evoked by electrical stimulation of the attached dorsal roots with C-fibre and A,-fibre intensity, respectively, were reduced by N-type channel blocker ,-conotoxin GVIA and to a much lesser extent, by P/Q-type channel antagonist ,-agatoxin TK, and the L-type channel blockers verapamil, respectively. No difference was found between unidentified neurons and neurons projecting to the periaqueductal grey matter. This is the first quantitative description of the relative contribution of voltage-dependent Ca2+ channels to the synaptic transmission in lamina I of the spinal dorsal horn, which is essential in the processing of pain-related information in the central nervous system. [source] Protein kinase C, mediates ethanol withdrawal hyper-responsiveness of NMDA receptor currents in spinal cord motor neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2005Hui-Fang Li 1The present studies were designed to test the hypothesis that neuronal-specific protein kinase C, (PKC,) plays a critical role in acute ethanol withdrawal hyper-responsiveness in spinal cord. 2Patch-clamp studies were carried out in motor neurons in neonatal rat spinal cord slices. Postsynaptic currents were evoked by brief pulses of 2 mMN -methyl- D -aspartic acid (NMDA) in the presence of bicuculline methiodide 10 ,M; strychnine 5 ,M and tetrodotoxin 0.5 ,M. 3Both ethanol depression and withdrawal hyper-responsiveness of NMDA-evoked currents are dependent on increases in intracellular Ca2+. Blocking intracellular increase in Ca2+ by 30 mM 1,2-bis(2-aminophenoxy)-ethane- N,N,N,,N,-tetraacetic acid (BAPTA) not only decreased the ethanol-induced depression of NMDA-evoked currents (33±5% in control vs 20±3% in BAPTA, P<0.05) but also eliminated acute ethanol withdrawal hyper-responsiveness. 4Immunohistochemistry studies revealed that neonatal spinal cord motor neurons contain an abundance of nuclear PKC,. 5Exposure to ethanol (100 mM) induced PKC, translocation from the nucleus to cytoplasm in motor neurons. Pretreatment with the , -isozyme-specific peptide PKC inhibitor, ,V5-3, blocked ethanol-induced translocation and also blocked withdrawal hyper-responsiveness. 6The results show that PKC, mediates ethanol withdrawal hyper-responsiveness in spinal motor neurons; the results may be relevant to some symptoms of ethanol withdrawal in vivo. British Journal of Pharmacology (2005) 144, 301,307. doi:10.1038/sj.bjp.0706033 [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] Inverse relationship between seizure expression and extrasynaptic NMDAR function following chronic NMDAR inhibitionEPILEPSIA, Issue 2010Suzanne B. Bausch Summary We showed previously that electrographic seizures involving dentate granule cells in organotypic hippocampal slice cultures were dramatically reduced following chronic treatment with the NR2B-selective antagonist, Ro25,6981, but were increased following chronic treatment with the high-affinity competitive antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-APV). To begin to investigate the potential mechanisms underlying the differential effects of N -methyl- d -aspartate receptor (NMDAR) antagonists on seizures, electrophysiologic experiments were conducted in dentate granule cells in hippocampal slice cultures treated for the entire 17,21 day culture period with vehicle, Ro25,6981 or D-APV. Initial experiments revealed a lack of an association between miniature excitatory postsynaptic current (mEPSC) measures and seizures suggesting that shifts in mEPSC were unlikely to account for the differential effects of D-APV and Ro25,6981 on seizures. However, the amplitude of tonic NMDAR-mediated currents was reduced in cultures treated chronically with D-APV and dramatically enhanced in cultures treated chronically with Ro25,6981. Because tonic NMDAR currents are mediated primarily by extrasynaptic NMDAR, these data show an inverse relationship between changes in extrasynaptic NMDAR function and alterations in seizure expression. [source] Prokineticin 2 depolarizes paraventricular nucleus magnocellular and parvocellular neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007Erik A. Yuill Abstract Blind whole-cell patch-clamp techniques were used to examine the effects of prokineticin 2 (PK2) on the excitability of magnocellular (MNC), parvocellular preautonomic (PA), and parvocellular neuroendocrine (NE) neurons within the hypothalamic paraventricular nucleus (PVN) of the rat. The majority of MNC neurons (76%) depolarized in response to 10 nm PK2, effects that were eliminated in the presence of tetrodotoxin (TTX). PK2 also caused an increase in excitatory postsynaptic potential (EPSP) frequency, a finding that was confirmed by voltage clamp recordings demonstrating increases in excitatory postsynaptic current (EPSC) frequency. The depolarizing effects of PK2 on MNC neurons were also abolished by kynurenic acid (KA), supporting the conclusion that the effects of PK2 are mediated by the activation of glutamate interneurons within the hypothalamic slice. PA (68%) and NE (67%) parvocellular neurons also depolarized in response to 10 nm PK2. However, in contrast to MNC neurons, these effects were maintained in TTX, indicating that PK2 directly affects PA and NE neurons. PK2-induced depolarizations observed in PA and NE neurons were found to be concentration-related and receptor mediated, as experiments performed in the presence of A1MPK1 (a PK2 receptor antagonist) abolished the effects of PK2 on these subpopulations of neurons. The depolarizing effects of PK2 on PA and NE neurons were also shown to be abolished by PD 98059 (a mitogen activated protein kinase (MAPK) inhibitor) suggesting that PK2 depolarizes PVN parvocellular neurons through a MAPK signalling mechanism. In combination, these studies have identified separate cellular mechanisms through which PK2 influences the excitability of different subpopulations of PVN neurons. [source] Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor ,2 F77I point mutationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005D. W. Cope Abstract Zolpidem is a hypnotic benzodiazepine site agonist with some ,-aminobutyric acid (GABA)A receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of ,2 subunit (,2F77I) point mutant mice. Analysis of forebrain GABAA receptor expression with immunocytochemistry, quantitative [3H]muscimol and [35S] t-butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [3H]flunitrazepam and [3H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous ,2I77/I77 and ,2F77/F77 mice. However, quantitative immunoblot analysis of ,2I77/I77 hippocampi showed some increased levels of ,2, ,1, ,4 and , subunits, suggesting that differences between strains may exist in unassembled subunit levels, but not in assembled receptors. Zolpidem (1 µm) enhanced the decay of mIPSCs in CA1 pyramidal cells of control (C57BL/6J, ,2F77/F77) mice by ,,60%, and peak amplitude by ,,20% at 33,34 °C in vitro. The actions of zolpidem (100 nm or 1 µm) were substantially reduced in ,2I77/I77 mice, although residual effects included a 9% increase in decay and 5% decrease in peak amplitude. Similar results were observed in CA1 stratum oriens/alveus interneurons. At network level, the effect of zolpidem (10 µm) on carbachol-induced oscillations in the CA3 area of ,2I77/I77 mice was significantly different compared with controls. Thus, the ,2F77I point mutation virtually abolished the actions of zolpidem on GABAA receptors in the hippocampus. However, some residual effects of zolpidem may involve receptors that do not contain the ,2 subunit. [source] Ionic/Electronic Hybrid Materials Integrated in a Synaptic Transistor with Signal Processing and Learning FunctionsADVANCED MATERIALS, Issue 22 2010Qianxi Lai A synaptic transistor is fabricated by integrating ionic/electronic hybrid materials to emulate biological synapses with spike signal processing, learning, and memory functions. A potential spike generates transient ionic fluxes in a polymer layer in the transistor gate, triggering an excitatory postsynaptic current in the transistor drain. Temporally correlated pre- and post-synaptic spikes modify ions stored in the polymer, resulting in the nonvolatile modification of the transistor with spike-timing-dependent plasticity. [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] Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levelsNEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2009K. N. Browning Abstract, Pancreatic polypeptides such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility. Vagal efferent outflow to the GI tract is determined principally by tonic GABAergic synaptic inputs onto dorsal motor nucleus of the vagus (DMV) neurons, yet neither peptide modulates GABAergic transmission. We showed recently that opioid peptides appear similarly ineffective because of the low resting cAMP levels. Using whole cell recordings from identified DMV neurons, we aimed to correlate the influence of brainstem cAMP levels with the ability of pancreatic polypeptides to modulate GABAergic synaptic transmission. Neither NPY, PYY, nor the Y1 or Y2 receptor selective agonists [Leu,Pro]NPY or NPY(3-36) respectively, inhibited evoked inhibitory postsynaptic current (eIPSC) amplitude unless cAMP levels were elevated by forskolin or 8-bromo-cAMP, by exposure to adenylate cyclase-coupled modulators such as cholecystokinin octapeptide (sulfated) (CCK-8s) or thyrotropin releasing hormone (TRH), or by vagal deafferentation. The inhibition of eIPSC amplitude by [Leu,Pro]NPY or NPY(3-36) was stable for approximately 30 min following the initial increase in cAMP levels. Thereafter, the inhibition declined gradually until the agonists were again ineffective after 60 min. Analysis of spontaneous and miniature currents revealed that such inhibitory effects were due to actions at presynaptic Y1 and Y2 receptors. These results suggest that, similar to opioid peptides, the effects of pancreatic polypeptides on GABAergic transmission depend upon the levels of cAMP within gastric inhibitory vagal circuits. [source] Seizures, enhanced excitation, and increased vesicle number in Lis1 mutant mice,ANNALS OF NEUROLOGY, Issue 5 2009Joel S.F. Greenwood PhD Objective In humans, abnormal neuronal migration and severe neuronal disorganization resulting from Lis1 (lissencephaly) haploinsufficiency contributes to cognitive impairment and seizures early in life. In Lis1 heterozygotic mice, severe hippocampal disorganization and cognitive impairment have also been reported. Using this mouse model, we examined the functional impact of LIS1 deficiency with particular focus on excitatory glutamate-mediated synaptic transmission. Methods We used visualized patch-clamp recordings in acute hippocampal slices. We recorded spontaneous, miniature and stimulation-evoked excitatory postsynaptic current (EPSC). Additional mice were processed for immunohistochemistry, electron microscopy (EM), or video-electroencephalographic (EEG) monitoring. Results Video-EEG confirmed the presence of spontaneous electrographic seizures in Lis1 mutant mice. In disorganized hippocampal slices from Lis1+/, mice, we noted a nearly two-fold significant increase in the frequency of spontaneous and miniature EPSC; no significant change in amplitude or decay was noted. Synaptic function assessed using brief repetitive or paired-pulse stimulation protocols, also revealed significant enhancement of glutamate-mediated excitation. Low concentrations of cadmium, a nonspecific blocker of voltage-dependent calcium channels mediating vesicle release, effectively restored paired-pulse facilitation deficits back to control levels. Analysis of synapse ultrastructure at the EM level identified a large increase in synaptic vesicle number. Interpretation Seizure activity, possibly associated with increased glutamate-mediated excitation and an increased pool of vesicles at the presynaptic site, was demonstrated in a mouse model of type I lissencephaly. Ann Neurol 2009;66:644,653 [source] Watching moving images specifically promotes development of medial area of secondary visual cortex in ratDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009Baonan Sun Abstract It is generally accepted that the cortex can be divided into numerous regions depending on the type of information each processes, and that specific input is effective in improving the development of related regions. In visual cortex, many subareas are distinguished on the basis of their adequate information. However, whether the development of a subarea can be specifically improved by its particular input is still largely unknown. Here, we show the specific effects of motion information on the development of the medial area of secondary visual cortex (V2M), a subarea associated with processing the movement component of visual information. Although watching a moving or a still image had similar effects in primary visual cortex, the moving image induced multistage development of V2M in dark-reared rats: both mRNA and protein levels of GluR2 were upregulated, the density and protein content of GluR2-positive synapses increased, and the spine density and the frequency of spontaneous excitatory postsynaptic currents (EPSCs) of pyramidal neurons in Layer 5 were elevated. Our results suggest that rats are able to identify motion information, distribute it to V2M, and then use this input to specifically improve the development of V2M. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Nicotinic synapses formed between chick ciliary ganglion neurons in culture resemble those present on the neurons in vivoDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2001Min Chen Abstract We studied nicotinic synapses between chick ciliary ganglion neurons in culture to learn more about factors influencing their formation and receptor subtype dependence. After 4,8 days in culture, nearly all neurons displayed spontaneous excitatory postsynaptic currents (sEPSCs), which occurred at about 1 Hz. Neurons treated with tetrodotoxin displayed miniature EPSCs (mEPSCs), but these occurred at low frequency (0.1 Hz), indicating that most sEPSCs are actually impulse driven. The sEPSCs could be classified by decay kinetics as fast, slow, or biexponential and, reminiscent of the situation in vivo, were mediated by two major nicotinic acetylcholine receptor (AChR) subtypes. Fast sEPSCs were blocked by ,-bungarotoxin (,Bgt), indicating dependence on ,Bgt-AChRs, most of which are ,7 subunit homopentamers. Slow sEPSCs were unaffected by ,Bgt, and were blocked instead by the ,3/,2-selective ,-conotoxin-MII (,CTx-MII), indicating dependence on ,3*-AChRs, which lack ,7 and contain ,3 subunits. Biexponential sEPSCs were mediated by both ,Bgt- and ,3*-AChRs because they had fast and slow components qualitatively similar to those comprising simple events, and these were reduced by ,Bgt and blocked by ,CTx-MII, respectively. Fluorescence labeling experiments revealed both ,Bgt- and ,3*-AChR clusters on neuron somata and neurites. Colabeling with antisynaptic vesicle protein antibody suggested that some ,3*-AChR clusters, and a few ,Bgt-AChR clusters are associated with synaptic sites, as is the case in vivo. These findings demonstrate the utility of ciliary ganglion neuron cultures for studying the regulation of nicotinic synapses, and suggest that mixed AChR subtype synapses characteristic of the neurons in vivo can form in the absence of normal inputs or targets. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 265,279, 2001 [source] Interneuron subtype specific activation of mGluR1/5 during epileptiform activity in hippocampusEPILEPSIA, Issue 8 2010Nathalie T Sanon Summary Purpose:, Specific inhibitory interneurons in area CA1 of the hippocampus, notably those located in stratum oriens,alveus (O/A-INs), are selectively vulnerable in patients and animal models of temporal lobe epilepsy (TLE). The excitotoxic mechanisms underlying the selective vulnerability of interneurons have not been identified but could involve group I metabotropic glutamate receptor subtypes (mGluR1/5), which have generally proconvulsive actions and activate prominent cationic currents and calcium responses specifically in O/A-INs. Methods:, In this study, we examine the role of mGluR1/5 in interneurons during epileptiform activity using whole-cell recordings from CA1 O/A-INs and selective antagonists of mGluR1, (LY367385) and mGluR5 (MPEP) in a disinhibited rat hippocampal slice model of epileptiform activity. Results:, Our data indicate more prominent epileptiform burst discharges and paroxysmal depolarizations (PDs) in O/A-INs than in interneurons located at the border of strata radiatum and lacunosum/moleculare (R/LM-INs). In addition, mGluR1 and mGluR5 significantly contributed to epileptiform responses in O/A-INs but not in R/LM-INs. Epileptiform burst discharges in O/A-INs were partly dependent on mGluR5. PDs and associated postsynaptic currents were dependent on both mGluR1, and mGluR5. These receptors contributed differently to postsynaptic currents underlying PDs, with mGluR5 contributing to the fast and slow components and mGluR1, to the slow component. Discussion:, These findings support interneuron subtype-specific activation and differential contributions of mGluR1, and mGluR5 to epileptiform activity in O/A-INs, which could be important for their selective vulnerability in TLE. [source] N -methyl- d -aspartate, hyperpolarization-activated cation current (Ih) and ,-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Mohamed Ouardouz Abstract Febrile seizures are the most common types of seizure in children, and are generally considered to be benign. However, febrile seizures in children with dysgenesis have been associated with the development of temporal lobe epilepsy. We have previously shown in a rat model of dysgenesis (cortical freeze lesion) and hyperthermia-induced seizures that 86% of these animals developed recurrent seizures in adulthood. The cellular changes underlying the increased risk of epileptogenesis in this model are not known. Using whole cell patch-clamp recordings from CA1 hippocampal pyramidal cells, we found a more pronounced increase in excitability in rats with both hyperthermic seizures and dysgenesis than in rats with hyperthermic seizures alone or dysgenesis alone. The change was found to be secondary to an increase in N -methyl- d -aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs). Inversely, hyperpolarization-activated cation current was more pronounced in naďve rats with hyperthermic seizures than in rats with dysgenesis and hyperthermic seizures or with dysgenesis alone. The increase in GABAA -mediated inhibition observed was comparable in rats with or without dysgenesis after hyperthermic seizures, whereas no changes were observed in rats with dysgenesis alone. Our work indicates that in this two-hit model, changes in NMDA receptor-mediated EPSCs may facilitate epileptogenesis following febrile seizures. Changes in the hyperpolarization-activated cation currents may represent a protective reaction and act by damping the NMDA receptor-mediated hyperexcitability, rather than converting inhibition into excitation. These findings provide a new hypothesis of cellular changes following hyperthermic seizures in predisposed individuals, and may help in the design of therapeutic strategies to prevent epileptogenesis following prolonged febrile seizures. [source] Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoidsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2010Véronique M. André Abstract Striatal medium-sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter gene to identify MSSNs containing D1 or D2 receptor subtypes were used to examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices and postsynaptic N -methyl- d -aspartate (NMDA) and ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents in acutely isolated cells. The results demonstrated dopamine receptor-specific modulation of sEPSCs. Dopamine and D1 agonists increased sEPSC frequency in D1 receptor-expressing MSSNs (D1 cells), whereas dopamine and D2 agonists decreased sEPSC frequency in D2 receptor-expressing MSSNs (D2 cells). These effects were fully (D1 cells) or partially (D2 cells) mediated through retrograde signaling via endocannabinoids. A cannabinoid 1 receptor (CB1R) agonist and a blocker of anandamide transporter prevented the D1 receptor-mediated increase in sEPSC frequency in D1 cells, whereas a CB1R antagonist partially blocked the decrease in sEPSC frequency in D2 cells. At the postsynaptic level, low concentrations of a D1 receptor agonist consistently increased NMDA and AMPA currents in acutely isolated D1 cells, whereas a D2 receptor agonist decreased these currents in acutely isolated D2 cells. These results show that both glutamate release and postsynaptic excitatory currents are regulated in opposite directions by activation of D1 or D2 receptors. The direction of this regulation is also specific to D1 and D2 cells. We suggest that activation of postsynaptic dopamine receptors controls endocannabinoid mobilization, acting on presynaptic CB1Rs, thus modulating glutamate release differently in glutamate terminals projecting to D1 and D2 cells. [source] Attention , oscillations and neuropharmacologyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Gustavo Deco Abstract Attention is a rich psychological and neurobiological construct that influences almost all aspects of cognitive behaviour. It enables enhanced processing of behaviourally relevant stimuli at the expense of irrelevant stimuli. At the cellular level, rhythmic synchronization at local and long-range spatial scales complements the attention-induced firing rate changes of neurons. The former is hypothesized to enable efficient communication between neuronal ensembles tuned to spatial and featural aspects of the attended stimulus. Recent modelling studies suggest that the rhythmic synchronization in the gamma range may be mediated by a fine balance between N -methyl- d -aspartate and ,-amino-3-hydroxy-5-methylisoxazole-4-propionate postsynaptic currents, whereas other studies have highlighted the possible contribution of the neuromodulator acetylcholine. This review summarizes some recent modelling and experimental studies investigating mechanisms of attention in sensory areas and discusses possibilities of how glutamatergic and cholinergic systems could contribute to increased processing abilities at the cellular and network level during states of top-down attention. [source] A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Richardson N. Leăo Abstract Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na+ channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na+ imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na+ clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na+ gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K+ currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a ,dual' firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials). [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] Suppression of excitatory cholinergic synaptic transmission by Drosophila dopamine D1-like receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007Ning Yuan Abstract The physiological function of dopamine is mediated through its G-protein-coupled receptor family. In Drosophila, four dopamine receptors have been molecularly characterized so far. However, due largely to the absence of a suitable preparation, the role of Drosophila dopamine receptors in modulating central synaptic transmission has not been examined. The present study investigated mechanisms by which dopamine modulates excitatory cholinergic synaptic transmission in Drosophila using primary neuronal cultures. Whole-cell recordings demonstrated that cholinergic excitatory postsynaptic currents (EPSCs) were down-regulated by focally applied dopamine (10,500 µm). The vertebrate D1 specific agonists SKF38393 and 6-chloro-APB (10 µm) mimicked dopamine-mediated suppression of cholinergic synaptic transmission with higher potency. In contrast, the D2 agonists quinpirole and bromocriptine did not alter cholinergic EPSCs, demonstrating that dopamine-mediated suppression of cholinergic synaptic transmission is specifically through activation of Drosophila D1-like receptors. Biophysical analysis of miniature EPSCs indicated that cholinergic suppression by activation of D1-like receptors is presynaptic in origin. Dopamine modulation of cholinergic transmission is not mediated through the cAMP/protein kinase A signaling pathway as cholinergic suppression by dopamine occurred in the presence of the protein kinase A inhibitor H-89. In addition, an adenylate cyclase activator, forskolin, led to an increase, not a decrease, of cholinergic EPSC frequency. Finally, we showed that activation of D1-like receptors decreased the frequency of action potentials in cultured Drosophila neurons by inhibiting excitatory cholinergic transmission. All our data demonstrated that activation of D1-like receptors in Drosophila neurons negatively modulates excitatory cholinergic synaptic transmission and thus inhibits neuronal excitability. [source] Vasopressin modulates lateral septal network activity via two distinct electrophysiological mechanismsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007G. Allaman-Exertier Abstract The lateral septal area is rich in vasopressin V1A receptors and is densely innervated by vasopressinergic axons, originating mainly from the bed nucleus of the stria terminalis and the amygdala. Genetic and behavioral studies provide evidence that activation of vasopressin receptors in this area plays a determinant role in promoting social recognition. What could be the neuronal mechanism underlying this effect? Using rat brain slices and whole-cell recordings, we found that lateral septal neurons are under the influence of a basal GABAergic inhibitory input. Vasopressin, acting via V1A but not V1B receptors, greatly enhanced this input in nearly all neurons. The peptide had no effect on miniature inhibitory postsynaptic currents, indicating that it acted on receptors located in the somatodendritic membrane, rather than on axon terminals, of GABAergic interneurons. Cell-attached recordings showed that vasopressin can cause a direct excitation of a subpopulation of lateral septal neurons by acting via V1A but not V1B receptors. The presence in the lateral septum of V1A but not of V1B receptors was confirmed by competition binding studies using light microscopic autoradiography. In conclusion, vasopressin appears to act in the lateral septum in a dual mode: (i) by causing a direct excitation of a subpopulation of neurons, and (ii) by causing an indirect inhibition of virtually all lateral septal neurons. This modulation by vasopressin of the lateral septal circuitry may be part of the neuronal mechanism by which the peptide, acting via V1A receptors, promotes social recognition. [source] Diversity of GABAA receptor synaptic currents on individual pyramidal cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007Timothy Ing Abstract Miniature GABAA receptor-mediated inhibitory postsynaptic currents (mIPSCs) in cortical pyramidal neurons have previously been categorized into two types: small amplitude mIPSCs with a mono-exponential deactivation (mono-mIPSCs) and relatively larger mIPSCs with bi-exponential deactivation (bi-mIPSCs). The aim of this study was to determine if the GABAA channels that underlie these mIPSCSs are molecularly distinct. We found, using non-stationary noise analysis, that the difference in their amplitude could be not accounted for by their single channel conductance (both were 40 pS). Next, using , subunit selective GABAA receptor modulators, we examined the identity of the , subunits that may be expressed in the synapses that give rise to these mIPSCs. Zolpidem (100 and 500 nm, ,1 selective) affected the deactivation of a subset of the mono-mIPSCs, indicating that ,1 subunits are not highly expressed in these synapses. However, zolpidem (100 nm) prolonged the deactivation of all bi-mIPSCs, indicating a high abundance of ,1 subunits in these synapses. SB-205384 (,3 selective) had no effect on the mono-mIPSCs but the bi-mIPSCs were prolonged. Furosemide (,4 selective) reduced the amplitude of only the mono-mIPSCs. L655,708 (,5 selective) reduced the amplitude of both populations and shortened the duration of the mono-mIPSCs. Finally, we found that the neuroactive steroid pregesterone sulphate reduced the amplitude of both mIPSC types. These results provide pharmacological evidence that synapses on cortical pyramidal neurons are molecularly distinct. The purpose of these different types of synapses may be to provide different inhibitory timing patterns on these cells. [source] Enhanced synaptic excitation,inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007F. 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] Selective 5-HT1B receptor inhibition of glutamatergic and GABAergic synaptic activity in the rat dorsal and median rapheEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Julia C. Lemos Abstract The dorsal (DR) and median (MR) raphe nuclei contain 5-hydroxytryptamine (5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain. The DR and MR have differential roles in mediating stress, anxiety and depression. Glutamate and GABA activity sculpt putative 5-HT neuronal firing and 5-HT release in a seemingly differential manner in the MR and DR, yet isolated glutamate and GABA activity within the DR and MR has not been systematically characterized. Visualized whole-cell voltage-clamp techniques were used to record excitatory and inhibitory postsynaptic currents (EPSC and IPSC) in 5-HT-containing neurons. There was a regional variation in action potential-dependent (spontaneous) and basal [miniature (m)] glutamate and GABAergic activity. mEPSC activity was greater than mIPSC activity in the DR, whereas in the MR the mIPSC activity was greater. These differences in EPSC and IPSC frequency indicate that glutamatergic and GABAergic input have distinct cytoarchitectures in the DR and MR. 5-HT1B receptor activation decreased mEPSC frequency in the DR and the MR, but selectively inhibited mIPSC activity only in the MR. This finding, in concert with its previously described function as an autoreceptor, suggests that 5-HT1B receptors influence the ascending 5-HT system through multiple mechanisms. The disparity in organization and integration of glutamatergic and GABAergic input to DR and MR neurons and their regulation by 5-HT1B receptors may contribute to the distinction in MR and DR regulation of forebrain regions and their differential function in the aetiology and pharmacological treatment of psychiatric disease states. [source] Nicotine withdrawal suppresses nicotinic modulation of long-term potentiation induction in the hippocampal CA1 regionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2006Yoshihiko Yamazaki Abstract We have previously reported that acute and chronic nicotine exposure lower the threshold for long-term potentiation (LTP) induction in the rat hippocampal CA1 region, and acute application of nicotine in the chronic-nicotine-treated hippocampus further reduces the threshold. However, it is unknown how withdrawal from chronic nicotine exposure affects the induction of LTP. Here, we show that, following nicotine withdrawal, the threshold for LTP induction fluctuates before returning to the basal level and acute nicotine is no longer effective in lowering the threshold at 4 days after withdrawal. Chronic nicotine-induced enhancement of N -methyl- d -aspartate receptor responses slowly diminishes and returns to the control level by 8 days of withdrawal. In 4-day-withdrawn hippocampi, there is functional up-regulation of postsynaptic ,7 nicotinic acetylcholine receptors (nAChRs) on interneurons in the stratum radiatum, whereas the release of ,-aminobutyric acid from their terminals is reduced. In both control and chronic nicotine-exposed hippocampi, acute nicotine depresses monosynaptic inhibitory postsynaptic currents recorded in pyramidal cells but has almost no effect at 4 days of withdrawal. The lack of effect is due, at least in part, to the loss of a presynaptic nicotine effect. These withdrawal-induced changes are accompanied by decreases in normal nicotine-induced enhancement of N -methyl- d -aspartate receptor responses, which may be responsible for the lack of acute nicotine-mediated facilitation of LTP induction in 4-day-withdrawn hippocampi. These withdrawal-induced changes may contribute to the cellular basis of unpleasant withdrawal symptoms and, thus, nicotine dependence. [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] Molecular analysis of the A322D mutation in the GABAA receptor ,1 -subunit causing juvenile myoclonic epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Klaus Krampfl Abstract Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the ,1 -subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing ,1 -, ,2 - and ,2 -subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose,response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures. [source] Dopamine D1-like receptor modulates layer- and frequency-specific short-term synaptic plasticity in rat prefrontal cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005Clint E. Young Abstract The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, <,10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 × 50 Hz) induced a homosynaptic PTP (decayed: ,1 min). The D1-like antagonist SCH23390 (1 µm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting ,4 min, but only at 2× intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V,V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting ,6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V,V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III,V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing. [source] Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Eduardo D. Martín Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source] Activity-dependent maturation of excitatory synaptic connections in solitary neuron cultures of mouse neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Naoki Takada Abstract Activity plays important roles in the formation and maturation of synaptic connections. We examined these roles using solitary neocortical excitatory neurons, receiving only self-generated synaptic inputs, cultured in a microisland with and without spontaneous spike activity. The amplitude of excitatory postsynaptic currents (EPSCs), evoked by applying brief depolarizing voltage pulses to the cell soma, continued to increase from 7 to 14 days in culture. Short-term depression of EPSCs in response to paired-pulse or 10-train-pulse stimulation decreased with time in culture. These developmental changes were prevented when neurons were cultured in a solution containing tetrodotoxin (TTX). The number of functional synapses estimated by recycled synaptic vesicles with FM4-64 was significantly smaller in TTX-treated than control neurons. However, the miniature EPSC amplitude remained unchanged during development, irrespective of activity. Transmitter release probability, assessed by use-dependent blockade of N -methyl- d -aspartate receptor-mediated EPSCs with MK-801, was higher in TTX-treated than control neurons. Therefore, the activity-dependent increase in EPSC amplitude was mainly ascribed to the increase in synapse number, while activity-dependent alleviation of short-term depression was mostly ascribed to the decrease in release probability. The effect of activity blockade on short-term depression, but not EPSC amplitude, was reversed after 4 days of TTX removal, indicating that synapse number and release probability are controlled by activity in very different ways. These results demonstrate that activity regulates the conversion of immature synapses transmitting low-frequency input signals preferentially to mature synapses transmitting both low- and high-frequency signals effectively, which may be necessary for information processing in mature cortex. [source] GluR- and TrkB-mediated maturation of GABAA receptor function during the period of eye openingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Christian Henneberger Abstract Synapse maturation includes the shortening of postsynaptic currents, due to changes in the subunit composition of respective transmitter receptors. Patch clamp experiments revealed that GABAergic inhibitory postsynaptic currents (ISPCs) of superior colliculus neurons significantly shorten from postnatal day (P)1 to P21. The change started after P6 and was steepest between P12 and P15, i.e. around eye opening. It was accompanied by enhanced sensitivity to zolpidem and increased expression of GABAAR ,1 mRNA, whereas the level of ,3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level of ,1/,3. As ,1/,3 peaked when N -methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents reached their maximum (P12) it was asked whether NMDAR activity can shape the kinetics of GABAergic IPSCs. Cultured collicular neurons were treated with NMDA or NMDAR block, and it was found that the former resulted in faster and the latter in slower IPSC decay. Group I mGluR blockade had no effect. Experiments with bdnf,/, mice revealed that, with some delay, the increase of ,1/,3 mRNA also occurred in the chronic absence of brain-derived neurotrophic factor (BDNF) and, again, this was accompanied by the shortening of IPSCs. In addition, there was an age-dependent depression of IPSC amplitudes by endogenous BDNF, which might reflect the developmental increase in the expression of GABAAR ,2L, as opposed to ,2S. Together, these experiments suggest that the GABAAR , subunit switch and the associated change in the IPSC kinetics were specifically controlled by NMDAR activity and independent on the signalling through group I mGluRs or TrkB. [source] | |||||||||||||