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Dynamic range of GSK3α not GSK3β is essential for bidirectional synaptic plasticity at hippocampal CA3‐CA1 synapses
Author(s) -
Shahab Lion,
Plattner Florian,
Irvine Elaine E.,
Cummings Damian M.,
Edwards Frances A.
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.22362
Subject(s) - long term potentiation , neuroscience , synaptic plasticity , gsk 3 , hippocampal formation , metaplasticity , hippocampus , nonsynaptic plasticity , synaptic fatigue , psychology , biology , inhibitory postsynaptic potential , kinase , excitatory postsynaptic potential , microbiology and biotechnology , genetics , receptor
Glycogen synthase kinase‐3 (GSK3), particularly the isoform GSK3β, has been implicated in a wide range of physiological systems and neurological disorders including Alzheimer's Disease. However, the functional importance of GSK3α has been largely untested. The multifunctionality of GSK3 limits its potential as a drug target because of inevitable side effects. Due to its greater expression in the CNS, GSK3β rather than GSK3α has also been assumed to be of primary importance in synaptic plasticity. Here, we investigate bidirectional long‐term synaptic plasticity in knockin mice with a point mutation in GSK3α or GSK3β that prevents their inhibitory regulation. We report that only the mutation in GSK3α affects long‐term potentiation (LTP) and depression (LTD). This stresses the importance of investigating isoform specificity for GSK3 in all systems and suggests that GSK3α should be investigated as a drug target in cognitive disorders including Alzheimer's Disease. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.