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mGluR1‐β‐arrestin 2 Signaling Mediates Induction of Excitatory Synaptic Plasticity
Author(s) -
Eng Andrew,
Hedrick Tristan,
Swanson Geoffrey
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.935.4
Subject(s) - long term potentiation , metabotropic glutamate receptor , metabotropic glutamate receptor 1 , synaptic plasticity , metabotropic receptor , glutamate receptor , neuroscience , excitatory postsynaptic potential , chemistry , hippocampal formation , biology , receptor , biochemistry , inhibitory postsynaptic potential
A subset of seven‐transmembrane receptors (7TMRs) couple to both G protein‐ and β‐arrestin (βarr)‐mediated signaling pathways. Our objective is to determine if group I metabotropic glutamate receptors (mGluR1 and mGluR5) engage βarr signaling during the induction of synaptic plasticity in the CNS. In these experiments we tested the role of βarr‐Src‐MAPK signaling in the induction of plasticity at the hippocampal mossy fiber‐CA3 synapse.
We compared mGluR1‐dependent synaptic plasticity in patch clamp recordings from CA3 pyramidal neurons in hippocampal slices prepared from wildtype, βarr 1 and βarr 2 knockout mice. Potentiation of EPSCs induced by low frequency, paired stimulation of mossy fiber inputs to CA3 pyramidal neurons was absent in mice lacking βarr 2 (91 ± 7% n=9 for βarr 2 ‐/‐ , 125 ± 9% n=18 for wildtype, p=0.01) but intact in mice lacking βarr 1 (128 ± 11% n=8 for βarr 1 ‐/‐ , 122 ± 13% n=17 for wildtype, p=0.74). In contrast, high‐frequency stimulation that induced long‐term potentiation was unaffected by gene targeting of either βarr isoform (190 ± 23% n=9 for βarr 1 ‐/‐ , 153 ± 18% n=6 for wildtype, p=0.22; 163 ± 18% n=7 for βarr 2 ‐/‐ , 167 ± 14% n=6 for wildtype, p=0.89). Pharmacological dissection implicated ERK1/2 of the MAPK pathway (104 ± 8% n=6 for u0126‐treated slices, 139 ± 9% n=15 for vehicle slices, p=0.01), whereas the role of Src tyrosine kinases was equivocal (114 ± 8% n=9 for PP2‐treated slices, 139 ± 9% n=15 for vehicle slices, p=0.06).
These data reveal a novel signaling function for βarrs when coupled to mGluR1 and therefore yield insight into new strategies for therapeutic targeting of group I mGluRs, which in recent years has been pursued for a number of neuropathologies.
Research supported by R21 NS088916‐01 from NINDS to GTS.