期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 36, 页码 13211-13216出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1409394111
关键词
hippocampus; parvalbumin; basket cell; GPCR
资金
- Deutsche Forschungsgemeinschaft [BA 1582/2-1, EXC 1086]
- Project FOR2143
- Project BIOSS-2 A6
- Volkswagen Foundation
- Schram Foundation
- MotiVate Program of Freiburg University Clinics
Hippocampal principal cell (PC) assemblies provide the brain with a mnemonic representation of space. It is assumed that the formation of cell assemblies is supported by long-lasting modification of glutamatergic synapses onto perisomatic inhibitory interneurons (PIIs), which provide powerful feedback inhibition to neuronal networks. Repetitive activation of dentate gyrus PIIs by excitatory mossy fiber (MF) inputs induces Hebbian long-term potentiation (LTP). In contrast, long-term depression (LTD) emerges in the absence of PII activity. However, little is known about the molecular mechanisms underlying synaptic plasticity in PIIs. Here, we examined the role of group I metabotropic glutamate receptors 1 and 5 (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. In contrast, 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 Ca2+-dependent PKC. Two-photon imaging revealed that the intracellular Ca2+ rise necessary for MF-LTP was largely mediated by Ca2+-permeable AMPA receptors (CP-AMPARs), but less by NMDA receptors or mGluRs1/5. Thus, our data indicate that 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. We further propose that Hebbian activation of mGluRs1/5 gates PIIs into a readiness mode to promote MF-LTP, which, in turn, will support timed PII recruitment, thereby assisting in PC assembly formation.
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