MiRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.

ABSTRACT: Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABA_ARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing it

SUBMITTER: Welle TM 

PROVIDER: S-EPMC11549329 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature