title: Joint CP-AMPA and group I mGlu receptor activation is required for synaptic plasticity in dentate gyrus fast-spiking interneurons.
abstract: 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 Ca(2+)-dependent PKC. Two-photon imaging revealed that the intracellular Ca(2+) rise necessary for MF-LTP was largely mediated by Ca(2+)-permeable AMPA receptors (CP-AMPARs), but less by NMDA receptors or mGluRs1/5. Thus, our data indicate that fast Ca(2+) 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.
authors.affiliation: Institute for Physiology I, Systemic and Cellular Neurophysiology.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hainmueller
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Molecular Embryology.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
authors.affiliation: Institute for Physiology II, and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Akos
authors.initials: A
authors.lastname: Kulik
authors.affiliation: Institute for Physiology I, Systemic and Cellular Neurophysiology, bartos@physiologie.uni-freiburg.de.
authors.forename: Marlene
authors.initials: M
authors.lastname: Bartos
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002463:Cell Membrane Permeability; D003712:Dendrites / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation; D007395:Interneurons / Q000378:metabolism*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D019599:Mossy Fibers, Hippocampal; D009473:Neuronal Plasticity; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D011493:Protein Kinase C; D002118:Calcium
keywords: GPCR; basket cell; hippocampus; parvalbumin