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

被引:57
作者
Kerr, Angharad M. [1 ]
Reisinger, Ellen [1 ]
Jonas, Peter [1 ]
机构
[1] Univ Freiburg, Inst Physiol 1, D-79104 Freiburg, Germany
关键词
GABAergic interneurons; basket cells; hippocampus; Ca2+ sensor;
D O I
10.1073/pnas.0800621105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Previous studies revealed that synaptotagmin 1 is the major Ca2+ sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca2+ 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 Ca2+ sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.
引用
收藏
页码:15581 / 15586
页数:6
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