title: The role of Homer1c in metabotropic glutamate receptor-dependent long-term potentiation.
abstract: Group I metabotropic glutamate receptors (mGluR1/5) play a role in synaptic plasticity and they demonstrate direct interactions with the neuronal Homer1c protein. We have previously shown that Homer1c can restore the plasticity deficits in Homer1 knockout mice (H1-KO). Here, we investigated the role of Homer1c in mGluR-dependent synaptic plasticity in wild-type mice, H1-KO, and H1-KO mice overexpressing Homer1c (KO+H1c). We used a form of plasticity induced by activation of mGluR1/5 that transforms short-term potentiaion (STP) induced by a subthreshold theta burst stimulation into long-term potentiation (LTP). We have shown that although acute hippocampal slices from wild-type animals can induce LTP using this stimulation protocol, H1-KO only show STP. Gene delivery of Homer1c into the hippocampus of H1-KO mice rescued LTP to wild-type levels. This form of synaptic plasticity was dependent on mGluR5 but not mGluR1 activation both in wild-type mice and in KO+H1c. mGluR1/5-dependent LTP was blocked with inhibitors of the MEK-ERK and PI3K-mTOR pathways in KO+H1c mice. Moreover, blocking Homer1c-mGluR5 interactions prevented the maintenance of LTP in acute hippocampal slices from KO+H1c. These data indicate that Homer1c-mGluR5 interactions are necessary for mGluR-dependent LTP, and that mGluR1/5-dependent LTP involves PI3K and ERK activation.
authors.affiliation: Department of Neurology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Kenneth
authors.initials: K
authors.lastname: O'Riordan
authors.forename: Hilary
authors.initials: H
authors.lastname: Gerstein
authors.forename: Rikki
authors.initials: R
authors.lastname: Hullinger
authors.forename: Corinna
authors.initials: C
authors.lastname: Burger
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; D018094:Receptors, Metabotropic Glutamate
keywords: ERK; Homer1 knockout mice; hippocampus; mTOR; molecular switch