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Publication : Acute reorganization of postsynaptic GABA(A) receptors reveals the functional impact of molecular nanoarchitecture at inhibitory synapses.

First Author  Olah SS Year  2023
Journal  Cell Rep Volume  42
Issue  11 Pages  113331
PubMed ID  37910506 Mgi Jnum  J:353100
Mgi Id  MGI:7567277 Doi  10.1016/j.celrep.2023.113331
Citation  Olah SS, et al. (2023) Acute reorganization of postsynaptic GABA(A) receptors reveals the functional impact of molecular nanoarchitecture at inhibitory synapses. Cell Rep 42(11):113331
abstractText  Neurotransmitter receptors partition into nanometer-scale subdomains within the postsynaptic membrane that are precisely aligned with presynaptic neurotransmitter release sites. While spatial coordination between pre- and postsynaptic elements is observed at both excitatory and inhibitory synapses, the functional significance of this molecular architecture has been challenging to evaluate experimentally. Here we utilized an optogenetic clustering approach to acutely alter the nanoscale organization of the postsynaptic inhibitory scaffold gephyrin while monitoring synaptic function. Gephyrin clustering rapidly enlarged postsynaptic area, laterally displacing GABA(A) receptors from their normally precise apposition with presynaptic active zones. Receptor displacement was accompanied by decreased synaptic GABA(A) receptor currents even though presynaptic release probability and the overall abundance and function of synaptic GABA(A) receptors remained unperturbed. Thus, acutely repositioning neurotransmitter receptors within the postsynaptic membrane profoundly influences synaptic efficacy, establishing the functional importance of precision pre-/postsynaptic molecular coordination at inhibitory synapses.
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