Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.

Nat Neurosci 2011 Apr 6;14(4):487-94. Epub 2011 Mar 6.

Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois, USA.

The absence of the chloride channel CLC-3 in Clcn3(-/-) mice results in hippocampal degeneration with a distinct temporal-spatial sequence that resembles neuronal loss in temporal lobe epilepsy. We examined how the loss of CLC-3 might affect GABAergic synaptic transmission in the hippocampus. An electrophysiological study of synaptic function in hippocampal slices taken from Clcn3(-/-) mice before the onset of neurodegeneration revealed a substantial decrease in the amplitude and frequency of miniature inhibitory postsynaptic currents compared with those in wild-type slices. We found that CLC-3 colocalized with the vesicular GABA transporter VGAT in the CA1 region of the hippocampus. Acidification of inhibitory synaptic vesicles induced by Cl(-) showed a marked dependence on CLC-3 expression. The decrease in inhibitory transmission in Clcn3(-/-) mice suggests that the neurotransmitter loading of synaptic vesicles was reduced, which we attribute to defective vesicular acidification. Our observations extend the role of Cl(-) in inhibitory transmission from that of a postsynaptic permeant species to a presynaptic regulatory element.

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http://dx.doi.org/10.1038/nn.2775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072292PMC
April 2011
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