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Publication : Regulation of Recurrent Inhibition by Asynchronous Glutamate Release in Neocortex.

First Author  Deng S Year  2020
Journal  Neuron Volume  105
Issue  3 Pages  522-533.e4
PubMed ID  31806492 Mgi Jnum  J:358884
Mgi Id  MGI:7783768 Doi  10.1016/j.neuron.2019.10.038
Citation  Deng S, et al. (2020) Regulation of Recurrent Inhibition by Asynchronous Glutamate Release in Neocortex. Neuron 105(3):522-533.e4
abstractText  The timing and size of inhibition are crucial for dynamic excitation-inhibition balance and information processing in the neocortex. The underlying mechanism for temporal control of inhibition remains unclear. We performed dual whole-cell recordings from pyramidal cells (PCs) and nearby inhibitory interneurons in layer 5 of rodent neocortical slices. We found asynchronous release (AR) of glutamate occurs at PC output synapses onto Martinotti cells (MCs), causing desynchronized and prolonged firing in MCs and thus imprecise and long-lasting inhibition in neighboring PCs. AR is much stronger at PC-MC synapses as compared with those onto fast-spiking cells and other PCs, and it is also dependent on PC subtypes, with crossed-corticostriatal PCs producing the strongest AR. Moreover, knocking out synaptotagmin-7 substantially reduces AR strength and recurrent inhibition. Our results highlight the effect of glutamate AR on the operation of microcircuits mediating slow recurrent inhibition, an important mechanism for controlling the timing and size of cortical inhibition.
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