Joint CP-AMPA and group I mGlu receptor activation is required for synaptic plasticity in dentate gyrus fast-spiking interneurons

26.08.2014

Hainmüller T, Krieglstein K, Kulik A, Bartos M.

Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13211-6.

Proc Natl Acad Sci U S A        online article

Hippocampal principal cell assemblies provide the brain with a mnemonic represetation of space. The formation of cell assemblies is supported by long-lasting modification of glutamatergic synapses onto perisomatic inhibitory interneurons (PIIs). They provide powerful feedback inhibition to neuronal networks. Repetitive activation of MF inputs induces LTP. LTD emerges in the absence of PII activity. What are the molecular mechanisms underlying synaptic plasticity in PIIs? We examined the role of mGluRs1/5 in inducing plastic changes at MF-PII synapses. We found that mGluRs1/5 are located perisynaptically and that pharmacological block of mGluR1 or mGluR5 abolished MF-LTP. Their exogenous activation was insufficient to induce MF-LTP but cleared MF-LTD. No LTP could be elicited in PIIs loaded with blockers of G protein signaling and PKC. The intracellular Ca2+ rise necessary for MF-LTP was largely mediated by CP-AMPARs. Thus, fast Ca2+ signaling via CP-AMPARs and slow G protein-mediated signaling via mGluRs1/5 converge to a PKC-dependent molecular pathway to induce Hebbian MF-LTP. Hebbian activation of mGluRs1/5 gates PIIs into a readiness mode to promote MF-LTP, which, in turn, will support timed PII recruitment.