title: Dynamic range of GSK3α not GSK3β is essential for bidirectional synaptic plasticity at hippocampal CA3-CA1 synapses.
abstract: 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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, United Kingdom; Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: Lion
authors.initials: L
authors.lastname: Shahab
authors.forename: Florian
authors.initials: F
authors.lastname: Plattner
authors.forename: Elaine E
authors.initials: EE
authors.lastname: Irvine
authors.forename: Damian M
authors.initials: DM
authors.lastname: Cummings
authors.forename: Frances A
authors.initials: FA
authors.lastname: Edwards
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology* / Q000254:growth & development; D056654:CA3 Region, Hippocampal / Q000201:enzymology* / Q000254:growth & development; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D055879:Gene Knock-In Techniques; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007527:Isoenzymes; D008297:Male; D008822:Mice, Transgenic; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000201:enzymology*; D046509:Tissue Culture Techniques
chemical_list: D007527:Isoenzymes; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha
keywords: electrophysiology; glycogen synthase kinase-3; knockin mice; long-term depression; long-term potentiation