Biomedical subjects

Jean-Claude Lacaille

Publications and source records attributed to Jean-Claude Lacaille.

At least 19 recordsLinked to original sources

PubMed2006

Compartmentalized Ca(2+) channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity.

Hippocampal mossy fibers (MFs) innervate CA3 targets via anatomically distinct presynaptic elements: MF boutons (MFBs) innervate pyramidal cells (PYRs), whereas filopodial extensions (Fils) of MFBs innervate st. lucidum interneurons (SLINs). Surprisingly, the same high-frequency stimulation (HFS) protocol induces presynaptically expressed LTP and LTD at PYR and SLIN inputs, respectively. This differential distribution of plasticity indicates that neighboring, functionally divergent presynaptic elements along the same axon serve as autonomous computational elements capable of modifying release independently. Indeed we report that HFS persistently depresses voltage-gated calcium channel (VGCC) function in Fil terminals, leaving MFB VGCCs unchanged despite similar contributions of N- and P/Q-type VGCCs to transmission at each terminal. Selective Fil VGCC depression results from HFS-induced mGluR7 activation leading to persistent P/Q-type VGCC inhibition. Thus, mGluR7 localization to MF-SLIN terminals and not MFBs allows for MF-SLIN LTD expression via depressed presynaptic VGCC function, whereas MF-PYR plasticity proceeds independently of VGCC alterations.

Animals↗

PubMed2006

mGluR1/5 subtype-specific calcium signalling and induction of long-term potentiation in rat hippocampal oriens/alveus interneurones.

Hippocampal inhibitory interneurones demonstrate pathway- and synapse-specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long-term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two-photon calcium imaging and whole-cell recordings to determine the Ca2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluR1alpha and mGluR5) and their role in hebbian long-term potentiation (LTP) in oriens/alveus (O/A) interneurones. We demonstrate that mGluR1alpha activation elicits dendritic Ca2+ signals resulting from Ca2+ influx via transient receptor potential (TRP) channels and Ca2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca2+ transients mediated exclusively by intracellular Ca2+ release. Using Western blot analysis and immunocytochemistry, we show mGluR1alpha-specific extracellular signal-regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluR1alpha/TRP Ca2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluR1alpha-specific Ca2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone-specific Ca2+ signalling, critical in regulating synaptic excitability in hippocampal networks.

Animals↗

PubMed2006

GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression.

Tetanus-induced heterosynaptic depression in the hippocampus is a key cellular mechanism in neural networks implicated in learning and memory. A growing body of evidence indicates that glial cells are important modulators of synaptic functions, but very little is known about their role in heterosynaptic plasticity. We examined the role of glial cells in heterosynaptic depression, knowing that tetanization and NMDA application caused depression of synaptic field responses (fEPSPs) and induced Ca2+ rise in glial cells. Here we report that chelating Ca2+ in a glial syncytium interfered with heterosynaptic depression and NMDA-induced fEPSP depression, suggesting that Ca2+ activation of glial cells is necessary for heterosynaptic depression. The NMDA-induced Ca2+ rise in glial cells was sensitive to tetrodotoxin and reduced by the GABAB antagonist CGP55845. Both heterosynaptic depression and simultaneous Ca2+ activation of glial cells were prevented by CGP55845, suggesting an involvement of the GABAergic network in glial activation and heterosynaptic depression. Also, the GABAB agonist baclofen caused both a Ca2+ rise in glial cells and fEPSP depression. Heterosynaptic depression, as well as NMDA- and baclofen-induced depression, were attenuated by an A1 antagonist, cyclopentyl-theophylline, whereas glial cell activation was not, indicating a role of adenosine downstream of glial activation. Finally, heterosynaptic depression requires ATP degradation because ectonucleotidase inhibitors reduced this plasticity. Our work indicates that Ca2+ activation of glial cells is necessary for heterosynaptic depression, which involves the sequential interaction of Schaffer collaterals, the GABAergic network, and glia. Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses.

Adenosine A1 Receptor Antagonists↗

PubMed2006

Glial cells in synaptic plasticity.

Plasticity of synaptic transmission is believed to be the cellular basis for learning and memory, and depends upon different pre- and post-synaptic neuronal mechanisms. Recently, however, an increasing number of studies have implicated a third element in plasticity; the perisynaptic glial cell. Originally glial cells were thought to be important for metabolic maintenance and support of the nervous system. However, work in the past decade has clearly demonstrated active involvement of glia in stability and overall nervous system function as well as synaptic plasticity. Through specific modulation of glial cell function, a wide variety of roles for glia in synaptic plasticity have been uncovered. Furthermore, interesting circumstantial evidence suggests a glial involvement in multiple other types of plasticity. We will discuss recent advances in neuron-glial interactions that take place during synaptic plasticity and explore different plasticity phenomena in which glial cells may be involved.

Animals↗

PubMed2006

Selective degeneration and synaptic reorganization of hippocampal interneurons in a chronic model of temporal lobe epilepsy.

Synaptic properties and connectivity of GABAergic inhibitory interneurons are modified in CA1 hippocampus of the KA model of epilepsy (Fig. 1). These changes affect interneurons that target dendritic areas of principal cells and have important consequences for network activity and hyperexcitability. Some of these changes contribute to hyperexcitability, while others likely develop to compensate for the hyperexcitability of the network. However, some of these "compensatory" changes might also paradoxically contribute to hyperexcitability and epileptogenesis.

Afferent Pathways↗

PubMed2005

Cell type-specific changes in spontaneous and minimally evoked excitatory synaptic activity in hippocampal CA1 interneurons of kainate-treated rats.

The epileptiform activity in the kainic acid (KA) model of epilepsy arises from complex changes in excitation and inhibition. To assess the involvement of excitatory drive onto inhibitory interneurons in this epileptiform activity, we examined changes in spontaneous and minimally evoked excitatory post-synaptic currents (sEPSCs and eEPSCs) in CA1 interneurons in stratum oriens/alveus (O/A) and stratum radiatum (RAD) in rat hippocampal slices after KA treatment. The frequency and amplitude of sEPSCs and the amplitude of eEPSCs were unchanged in O/A interneurons, but the EPSC kinetics were significantly slower. These changes appear to be due to altered kinetics and voltage-dependent properties of the NMDA component of EPSCs in O/A interneurons. In contrast, sEPSCs and eEPSCs in RAD interneurons did not change after KA treatment. The distinct changes in excitatory synaptic activity in interneurons differentially involved in feedback (O/A) versus feedforward (RAD) inhibition suggest a cell type-specific reorganization of excitatory synapses after KA treatment. These modifications in excitatory input to interneurons could contribute to the maintenance of inhibition of CA1 pyramidal cells after KA treatment, or may also create network conditions favourable to epileptiform activity.

Animals↗

PubMed2005

Characterization of an RNA granule from developing brain.

In brain, mRNAs are transported from the cell body to the processes, allowing for local protein translation at sites distant from the nucleus. Using subcellular fractionation, we isolated a fraction from rat embryonic day 18 brains enriched for structures that resemble amorphous collections of ribosomes. This fraction was enriched for the mRNA encoding beta-actin, an mRNA that is transported in dendrites and axons of developing neurons. Abundant protein components of this fraction, determined by tandem mass spectrometry, include ribosomal proteins, RNA-binding proteins, microtubule-associated proteins (including the motor protein dynein), and several proteins described only as potential open reading frames. The conjunction of RNA-binding proteins, transported mRNA, ribosomal machinery, and transporting motor proteins defines these structures as RNA granules. Expression of a subset of the identified proteins in cultured hippocampal neurons confirmed that proteins identified in the proteomics were present in neurites associated with ribosomes and mRNAs. Moreover many of the expressed proteins co-localized together. Time lapse video microscopy indicated that complexes containing one of these proteins, the DEAD box 3 helicase, migrated in dendrites of hippocampal neurons at the same speed as that reported for RNA granules. Although the speed of the granules was unchanged by activity or the neurotrophin brain-derived neurotrophic factor, brain-derived neurotrophic factor, but not activity, increased the proportion of moving granules. These studies define the isolation and composition of RNA granules expressed in developing brain.

Actins↗

PubMed2005

Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2.

Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2(-/-) mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2(-/-) slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2(-/-) mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2(-/-) mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway.

Animals↗

PubMed2005

Differential regulation of metabotropic glutamate receptor- and AMPA receptor-mediated dendritic Ca2+ signals by presynaptic and postsynaptic activity in hippocampal interneurons.

Calcium plays a crucial role as a ubiquitous second messenger and has a key influence in many forms of synaptic plasticity in neurons. The spatiotemporal properties of dendritic Ca2+ signals in hippocampal interneurons are relatively unexplored. Here we use two-photon calcium imaging and whole-cell recordings to study properties of dendritic Ca2+ signals mediated by different glutamate receptors and their regulation by synaptic activity in oriens/alveus (O/A) interneurons of rat hippocampus. We demonstrate that O/A interneurons express Ca2+-permeable AMPA receptors (CP-AMPARs) providing fast Ca2+ signals. O/A cells can also coexpress CP-AMPARs, Ca2+-impermeable AMPARs (CI-AMPARs), and group I/II metabotropic glutamate receptors (mGluRs) (including mGluR1a), in the same cell. CI-AMPARs are often associated with mGluRs, resulting in longer-lasting Ca2+ signals than CP-AMPAR-mediated responses. Finally, CP-AMPAR- and mGluR-mediated Ca2+ signals demonstrate distinct voltage dependence and are differentially regulated by presynaptic and postsynaptic activity: weak synaptic stimulation produces Ca2+ signals mediated by CP-AMPARs, whereas stronger stimulation, or weak stimulation coupled with postsynaptic depolarization, recruits Ca2+ signals mediated by mGluRs. Our results suggest that differential activation of specific glutamate receptor-mediated Ca2+ signals within spatially restricted dendritic microdomains may serve distinct signaling functions and endow oriens/alveus interneurons with multiple forms of Ca2+-mediated synaptic plasticity. Specific activation of mGluR-mediated Ca2+ signals by coincident presynaptic and postsynaptic activity fulfills the conditions for Hebbian pairing and likely underlies their important role in long-term potentiation induction at O/A interneuron synapses.

Animals↗

PubMed2005

Cell-type specific GABA synaptic transmission and activity-dependent plasticity in rat hippocampal stratum radiatum interneurons.

Abstract In hippocampal pyramidal cells, the efficacy of synaptic transmission at gamma-aminobutyric acid (GABA)ergic synapses, is modulated by activity. However, whether such plasticity occurs at inhibitory synapses on interneurons remains largely unknown. Using whole-cell voltage-clamp recordings of inhibitory postsynaptic currents (IPSCs) in Sprague-Dawley rat hippocampal slices, we examined whether GABA synapses of stratum radiatum interneurons were affected by stimulation protocols known to alter efficacy at inhibitory synapses of CA1 pyramidal cells. Monosynaptically evoked IPSCs (eIPSCs) exhibited different properties with significantly faster kinetics, higher coefficients of variation, a current-voltage (I-V) relationship shifted to depolarized values and a smaller paired-pulse depression, in interneurons than in pyramidal cells. GABA synapses on interneurons also showed a different capacity for plasticity. Indeed, theta-burst stimulation induced a long-term potentiation of eIPSCs in both cell types, but the induction mechanisms differed in interneurons, as it was not affected by antagonists of GABAB receptors and group I/II metabotropic glutamate receptors (mGluRs). Furthermore, 100-Hz tetanization selectively elicited a short-term depression of eIPSCs in pyramidal cells. A postsynaptic depolarization produced a transient suppression of eIPSCs (depolarization-induced suppression of inhibition) in pyramidal cells but not in interneurons. Spontaneous IPSCs were similarly reduced following depolarization in pyramidal cells, but not in interneurons. These results indicate that GABA synapses of stratum radiatum interneurons exhibit different properties and capacity for activity-dependent plasticity than those of pyramidal cells. This cell-type specific mode of transmission and adaptive regulation of GABA synapses may contribute to hippocampal plasticity and functions.

Animals↗

PubMed2005

Short-term effects of kainic acid on CA1 hippocampal interneurons differentially vulnerable to excitotoxicity.

PURPOSE: We sought to identify the inhibitory interneurons of the rat hippocampal CA1 region selectively vulnerable in the kainic acid (KA) model of temporal lobe epilepsy and to determine whether their selective vulnerability could be due to differential short-term KA effects. METHODS: We quantified vulnerable interneurons in stratum oriens-alveus (O/A) by using immunohistochemistry for glutamic acid decarboxylase (GAD), parvalbumin (PV), and somatostatin (SS) after KA injections in rats, and then compared in normal slices the effects of KA on interneurons either in O/A (vulnerable to KA) or in strata radiatum and lacunosum-moleculare (R/LM) (resistant to KA) by using whole-cell recording and calcium imaging. RESULTS: GAD-, PV- and SS-positive cells in O/A were decreased after KA treatment in P20 and P30 rats. Both short (1-min) and long (10-min) applications of KA produced similar tetrodotoxin (TTX)-insensitive membrane depolarization and decrease in input resistance in O/A and R/LM interneurons. KA responses were antagonized by CNQX and GYKI52466, suggesting AMPA receptor activation. KA also generated a similar increase in intracellular Ca2+ in O/A and R/LM interneurons, which was antagonized by CNQX and GYKI52466. CONCLUSIONS: The selective vulnerability of GAD-, PV-, and SS-immunopositive O/A interneurons in the KA model may not arise from cell-specific short-term membrane effects or calcium responses induced by KA, but from other glutamate receptor-mediated excitotoxic processes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2004

Group I metabotropic glutamate receptor actions in oriens/alveus interneurons of rat hippocampal CA1 region.

Group I metabotropic glutamate receptors (mGluRs) are important for hippocampal interneuron function. We used whole-cell recording and confocal imaging to characterize group I mGluR actions in CA1 oriens/alveus interneurons in slices. In tetrodotoxin and ionotropic glutamate receptor antagonists, the group I mGluR specific agonist DHPG increased intradendritic Ca(2+) levels and depolarized interneurons, whereas the group II mGluR specific agonist DCG-IV and the group III mGluR specific agonist L-AP4 did not. DHPG-induced depolarizing and Ca(2+) responses were antagonized by the group I mGluR antagonist 4CPG, but only Ca(2+) responses were significantly inhibited by the mGluR1 antagonist CPCCOEt. DHPG-induced depolarizing responses were not blocked by the inositol-1,4,5-trisphosphate (IP(3)) receptor inhibitor heparin, the protein kinase C (PKC) antagonists GF-109203X, or the inhibitor of phospholipase C (PLC) U73122. Thus, these responses to DHPG may not be transduced by the PLC-->IP(3)/diacylglycerol (DAG) pathway classically linked to group I mGluRs. DHPG-induced depolarizations were not blocked by intracellular GDP beta S or bath-application of N-ethylmaleimide (NEM), suggesting the involvement of a G protein-independent pathway. Our findings indicate that group I mGluRs induce a depolarization of oriens/alveus interneurons via a G protein-independent mechanism different from their classic signalling pathway. Since depolarizations are associated with intracellular Ca(2+) rises, these actions may be important for their synaptic plasticity and vulnerability to excitotoxicity.

Animals↗

PubMed2003

Synapse-specific mGluR1-dependent long-term potentiation in interneurones regulates mouse hippocampal inhibition.

Hippocampal CA1 inhibitory interneurones control the excitability and synchronization of pyramidal cells, and participate in hippocampal synaptic plasticity. Pairing theta-burst stimulation (TBS) with postsynaptic depolarization, we induced long-term potentiation (LTP) of putative single-fibre excitatory postsynaptic currents (EPSCs) in stratum oriens/alveus (O/A) interneurones of mouse hippocampal slices. LTP induction was absent in metabotropic glutamate receptor 1 (mGluR1) knockout mice, was correlated with the postsynaptic presence of mGluR1a, and required a postsynaptic Ca2+ rise. Changes in paired-pulse facilitation and coefficient of variation indicated that LTP expression involved presynaptic mechanisms. LTP was synapse specific, occurring selectively at synapses modulated by presynaptic group II, but not group III, mGluRs. Furthermore, the TBS protocol applied in O/A induced a long-term increase of polysynaptic inhibitory responses in CA1 pyramidal cells, that was absent in mGluR1 knockout mice. These results uncover the mechanisms of a novel form of interneurone synaptic plasticity that can adaptively regulate inhibition of hippocampal pyramidal cells.

Animals↗

PubMed2003

Depolarization-induced long-term depression at hippocampal mossy fiber-CA3 pyramidal neuron synapses.

Hippocampal CA3 pyramidal neurons receive two types of excitatory afferent innervation: mossy fibers (MFs) from granule cells of the dentate gyrus and recurrent collateral fibers (CFs) from other CA3 pyramidal neurons. At CF-CA3 pyramidal neuron synapses, membrane depolarization paired with low (0.33 Hz) presynaptic stimulation generated a heterogeneous response that ranged from long-term potentiation (LTP), long-term depression (LTD), to no alteration of synaptic strength. However, the same induction paradigm applied at MF-CA3 pyramidal neuron synapses consistently induced LTD. This novel form of LTD was independent of NMDARs, mGluRs, cannabinoid receptors, opioid receptors, or coincident synaptic activity, but was dependent on postsynaptic Ca2+ elevation through L-type Ca2+ channels and release from inositol 1,4,5-trisphosphate receptor-sensitive intracellular stores. Ca2+ imaging of both proximal and distal CA3 pyramidal neuron dendrites demonstrated that the depolarizing induction paradigm differentially elevated intracellular Ca2+ levels. L-type Ca2+ channel activation was observed only at the most proximal locations where mossy fibers make synapses. Depolarization-induced LTD did not occlude the conventional 1 Hz-induced LTD or vice versa, suggesting independent mechanisms underlie each form of plasticity. The paired-pulse ratio and coefficient of variation of synaptic transmission were unchanged after LTD induction, suggesting that the expression locus of LTD is postsynaptic. Moreover, peak-scaled nonstationary variance analysis indicated that depolarization-induced LTD correlated with a reduction in postsynaptic AMPA receptor numbers without a change in AMPA receptor conductance. Our results suggest that this novel form of LTD is selectively expressed at proximal dendritic locations closely associated with L-type Ca2+ channels.

Animals↗

PubMed2003

GABAB receptor- and metabotropic glutamate receptor-dependent cooperative long-term potentiation of rat hippocampal GABAA synaptic transmission.

Repetitive stimulation of Schaffer collaterals induces activity-dependent changes in the strength of polysynaptic inhibitory postsynaptic potentials (IPSPs) in hippocampal CA1 pyramidal neurons that are dependent on stimulation parameters. In the present study, we investigated the effects of two stimulation patterns, theta-burst stimulation (TBS) and 100 Hz tetani, on pharmacologically isolated monosynaptic GABAergic responses in adult CA1 pyramidal cells. Tetanization with 100 Hz trains transiently depressed both early and late IPSPs, whereas TBS induced long-term potentiation (LTP) of early IPSPs that lasted at least 30 min. Mechanisms mediating this TBS-induced potentiation were examined using whole-cell recordings. The paired-pulse ratio of monosynaptic inhibitory postsynaptic currents (IPSCs) was not affected during LTP, suggesting that presynaptic changes in GABA release are not involved in the potentiation. Bath application of the GABAB receptor antagonist CGP55845 or the group I/II metabotropic glutamate receptor antagonist E4-CPG inhibited IPSC potentiation. Preventing postsynaptic G-protein activation or Ca2+ rise by postsynaptic injection of GDP-beta-S or BAPTA, respectively, abolished LTP, indicating a G-protein- and Ca2+-dependent induction in this LTP. Finally during paired-recordings, activation of individual interneurons by intracellular TBS elicited solely short-term increases in average unitary IPSCs in pyramidal cells. These results indicate that a stimulation paradigm mimicking the endogenous theta rhythm activates cooperative postsynaptic mechanisms dependent on GABABR, mGluR, G-proteins and intracellular Ca2+, which lead to a sustained potentiation of GABAA synaptic transmission in pyramidal cells. GABAergic synapses may therefore contribute to functional synaptic plasticity in adult hippocampus.

Animals↗

PubMed2003

Different actions of gabapentin and baclofen in hippocampus from weaver mice.

The pre- and postsynaptic effects of baclofen, a broad-spectrum gamma-aminobutyric acid (GABA)B receptor agonist, and gabapentin, a selective agonist at GABA(B) receptors composed of GABA(B)(1a,2) heterodimers, were examined in CA1 pyramidal cells using whole-cell patch-clamp recordings in hippocampal slices from different strains of mice. In slices from C57BL/6 mice, by means of GABA(B) receptors, gabapentin and baclofen activated outward K+ currents at resting membrane potential. In weaver mice with a Kir3.2 channel mutation, baclofen and gabapentin failed to activate postsynaptic K+ currents. However, in littermate controls of weaver mice, gabapentin failed to evoke K+ currents, whereas baclofen activated currents in the same cells. Thus, postsynaptic actions of gabapentin and baclofen on K+ currents are different in this mouse strain. Via presynaptic GABA(B) receptors, baclofen significantly reduced GABA(A) inhibitory postsynaptic currents (IPSCs) in slices from C57BL/6 mice, as well as weaver and control mice. In contrast, gabapentin did not affect IPSCs significantly in any group of mice. These results indicate that although baclofen and gabapentin are agonists at postsynaptic GABA(B) receptors positively coupled to K+ channels, their mechanism of action differs in certain strains of mice, including the weaver wild-type mice, suggesting a dissociation in their signaling mechanism and coupling to K+ channels.

Acetates↗

PubMed2003

Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells.

Gabapentin is a clinically effective anticonvulsant with an unclear mechanism of action. It was described as a GABA(B(1a,2)) receptor subtype-selective agonist, activating postsynaptic K(+) currents and inhibiting postsynaptic Ca(2+) channels in CA1 pyramidal cells, but without presynaptic actions. These activities appeared controversial and we therefore sought to further clarify gabapentin actions in rat hippocampal slices by characterizing K(+) currents and Ca(2+) channels targeted by gabapentin using whole-cell recording and multiphoton Ca(2+) imaging. 1) We found that gabapentin and baclofen induced inwardly rectifying K(+) currents (K(Gbp) and K(Bac), respectively), sensitive to Ba(2+) and Cs(+). 2) A constitutively active K(IR) current, independent of GABA(B) receptor activation and sensitive to Ba(2+) and Cs(+) was also present. 3) K(Gbp), K(Bac), and K(IR) currents showed some differences in sensitivity to Ba(2+) and Cs(+), indicating the possible activation of distinct Kir3 currents, independent of K(IR), by gabapentin and baclofen. 4) Gabapentin inhibition of Ca(2+) channels was abolished by omega-conotoxin GVIA, but not by omega-agatoxin IVA and nimodipine, indicating a predominant action of gabapentin on N-type Ca(2+) channels. 5) Gabapentin actions were linked to activation of pertussis toxin-sensitive G-proteins since N-ethylmaleimide (NEM) blocked K(Gbp) activation and Ca(2+) channel inhibition by gabapentin. 6) Finally, gabapentin reduced epileptiform discharges in slices via GABA(B) receptor activation. The anticonvulsant actions of gabapentin in hippocampal cells may thus involve GABA(B) receptor coupling to G-proteins and modulation of Kir3 and N-type Ca(2+) channels. Moreover, gabapentin and baclofen activation of GABA(B) receptors may couple to distinct cellular targets.

Acetates↗

PubMed2003

Interneuron Diversity series: Hippocampal interneuron classifications--making things as simple as possible, not simpler.

The nervous system is made up of many specific types of neuron intricately intertwined to form complex networks. Identifying and defining the characteristic features of the many different neuronal types is essential for achieving a cellular understanding of complex activity from perception to cognition. So far, cortical GABAergic interneurons have represented the epitome of cellular diversity in the CNS. Despite the desperate need for effective classification criteria allowing a common language among neuroscientists, interneurons still evoke memories of Babel. Several approaches are now available to overcome the challenges and problems associated with the various classification systems used so far.

Animals↗