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Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons.

ABSTRACT: Inhibitory synaptic transmission in the hippocampus in mediated by a wide variety of different interneuron classes which are assumed to play different roles in network activity. Activation of presynaptic kainate receptors (KARs) has been shown to reduce inhibitory transmission but the interneuron class(es) at which they act is only recently beginning to emerge. Using paired recordings we show that KAR activation causes a decrease in presynaptic release from cholecystokinin (CCK)- but not parvalbumin-containing interneurons and that this decrease is observed when pyramidal cells, but not interneurons, are the postsynaptic target. We also show that although the synchronous release component is reduced, the barrage of asynchronous GABA release from CCK interneurons during sustained firing is unaffected by KAR activation. This indicates that presynaptic KARs preserve and act in concert with asynchronous release to switch CCK interneurons from a phasic inhibition mode to produce prolonged inhibition during periods of intense activity.

SUBMITTER: Daw MI

PROVIDER: S-EPMC2937572 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons.

Daw Michael I MI Pelkey Kenneth A KA Chittajallu Ramesh R McBain Chris J CJ

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100801 33

Inhibitory synaptic transmission in the hippocampus in mediated by a wide variety of different interneuron classes which are assumed to play different roles in network activity. Activation of presynaptic kainate receptors (KARs) has been shown to reduce inhibitory transmission but the interneuron class(es) at which they act is only recently beginning to emerge. Using paired recordings we show that KAR activation causes a decrease in presynaptic release from cholecystokinin (CCK)- but not parvalb ...[more]

PMID: 20720128

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Project description:UNLABELLED:Although synapsins regulate GABA release, it is unclear which synapsin isoforms are involved. We identified the synapsin isoforms that regulate GABA release via rescue experiments in cultured hippocampal neurons from synapsin I, II, and III triple knock-out (TKO) mice. In situ hybridization indicated that five different synapsin isoforms are expressed in hippocampal interneurons. Evoked IPSC amplitude was reduced in TKO neurons compared with triple wild-type neurons and was rescued by introducing any of the five synapsin isoforms. This contrasts with hippocampal glutamatergic terminals, where only synapsin IIa rescues the TKO phenotype. Deconvolution analysis indicated that the duration of GABA release was prolonged in TKO neurons and this defect in release kinetics was rescued by each synapsin isoform, aside from synapsin IIIa. Because release kinetics remained slow, whereas peak release rate was rescued, there was a 2-fold increase in GABA release in TKO neurons expressing synapsin IIIa. TKO neurons expressing individual synapsin isoforms showed normal depression kinetics aside from more rapid depression in neurons expressing synapsin IIIa. Measurements of the cumulative amount of GABA released during repetitive stimulation revealed that the rate of mobilization of vesicles from the reserve pool to the readily releasable pool and the size of the readily releasable pool of GABAergic vesicles were unaffected by synapsins. Instead, synapsins regulate release of GABA from the readily releasable pool, with all isoforms aside from synapsin IIIa controlling release synchrony. These results indicate that synapsins play fundamentally distinct roles at different types of presynaptic terminals. SIGNIFICANCE STATEMENT:Synapsins are a family of proteins that regulate synaptic vesicle (SV) trafficking within nerve terminals. Here, we demonstrate that release of the inhibitory neurotransmitter GABA is supported by many different synapsin types. This contrasts with the release of other neurotransmitters, which typically is supported by only one type of synapsin. We also found that synapsins serve to synchronize the release of GABA in response to presynaptic action potentials, which is different from the synapsin-dependent trafficking of SVs in other nerve terminals. Our results establish that different synapsins play fundamentally different roles at nerve terminals releasing different types of neurotransmitters. This is an important clue to understanding how neurons release their neurotransmitters, a process essential for normal brain function.

Project description:Schaffer collateral synapses in hippocampus show target-cell specific short-term plasticity. Using GFP-expressing Inhibitory Neuron (GIN) transgenic mice that express enhanced green fluorescent protein (EGFP) in a subset of somatostatin-containing interneurons (SOM interneurons), we previously showed that Schaffer collateral synapses onto SOM interneurons in stratum (S.) radiatum have unusually large (up to 6-fold) paired-pulse facilitation. This results from a low initial release probability and the enhancement of facilitation by synaptic activation of presynaptic kainate receptors. Here we further investigate the properties of these kainate receptors and examine their effects on short-term facilitation during physiologically derived stimulation patterns, using excitatory postsynaptic currents recorded in S. radiatum interneurons during Schaffer collateral stimulation in acute slices from juvenile GIN mice. We find that GluR5 and GluR6 antagonists decrease short-term facilitation at Schaffer collateral synapses onto SOM interneurons with no additive effects, suggesting that the presynaptic kainate receptors are heteromers containing both GluR5 and GluR6 subunits. The calcium-permeable receptor antagonist 1-napthyl acetyl spermine (NASPM) both mimics and occludes the effect of the kainate receptor antagonists, indicating that the presynaptic kainate receptors are calcium permeable. Furthermore, Schaffer collateral synapses onto SOM interneurons show up to 11-fold short-term facilitation during physiologically derived stimulus patterns, in contrast to other interneurons that have less than 1.5-fold facilitation. Blocking the kainate receptors reduces facilitation in SOM interneurons by approximately 50% during the physiologically derived patterns and reduces the dynamic range. Activation of calcium-permeable kainate receptors containing GluR5/GluR6 causes a dramatic increase in short-term facilitation during physiologically derived stimulus patterns, a mechanism likely to be important in regulating the strength of Schaffer collateral synapses onto SOM interneurons in vivo.

Dataset Information

Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons.

Publications

Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons.

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