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The role of Homer1c in metabotropic glutamate receptor‐dependent long‐term potentiation
Author(s) -
O'Riordan Kenneth,
Gerstein Hilary,
Hullinger Rikki,
Burger Corinna
Publication year - 2014
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22222
Subject(s) - metabotropic glutamate receptor , long term potentiation , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , synaptic plasticity , neuroscience , long term depression , chemistry , metabotropic receptor , nmda receptor , glutamate receptor , ampa receptor , biology , receptor , biochemistry
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. © 2013 Wiley Periodicals, Inc.