Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses Journal Article


Author(s): Kerr, Angharad M; Reisinger, Ellen; Jonas, Peter
Article Title: Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses
Affiliation
Abstract: Previous studies revealed that synaptotagmin 1 is the major Ca(2+) sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca(2+) sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC-BC synapses. However, synchronous release at inhibitory BC-GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC-GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1-5, 7, and 11-13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC-GC synapses. Thus, alternative fast Ca(2+) sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.
Keywords: Animals; Cells, Cultured; Mice; Mice, Knockout; Calcium/metabolism; Synapses/metabolism; Glutamic Acid/*metabolism; Synaptic Transmission/physiology; gamma-Aminobutyric Acid/metabolism; Hippocampus/metabolism; Synaptotagmin I/genetics/metabolism
Journal Title: PNAS
Volume: 105
Issue 40
ISSN: 1091-6490
Publisher: National Academy of Sciences  
Publication Place: United States
Date Published: 2008-01-01
Start Page: 15581
End Page: 6
DOI: 10.1073/pnas.0800621105
Open access: no