Relocation of an Extrasynaptic GABA_A Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory.

ABSTRACT: The excitatory synapse between hippocampal CA3 and CA1 pyramidal neurons exhibits long-term potentiation (LTP), a positive feedback process implicated in learning and memory in which postsynaptic depolarization strengthens synapses, promoting further depolarization. Without mechanisms for interrupting positive feedback, excitatory synapses could strengthen inexorably, corrupting memory storage. Here, we reveal a hidden form of inhibitory synaptic plasticity that prevents accumulation of excitatory LTP. We developed a knockin mouse that allows optical control of endogenous α5-subunit-containing γ-aminobutyric acid (GABA)_A receptors (α5-GABARs). Induction of excitatory LTP relocates α5-GABARs, which are ordinarily extrasynaptic, to inhibitory synapses, quashing further NMDA recept

SUBMITTER: Davenport CM 

PROVIDER: S-EPMC7790995 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature