Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses.
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.
Kerr
Angharad M
AM
Physiological Institute I, University of Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
Reisinger
Ellen
E
Jonas
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D050863:Synaptotagmin I; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium