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Glycogen synthase kinase‐3 inhibition is integral to long‐term potentiation
Author(s) -
Hooper Claudie,
Markevich Vladimir,
Plattner Florian,
Killick Richard,
Schofield Emma,
Engel Tobias,
Hernandez Felix,
Anderton Brian,
Rosenblum Kobi,
Bliss Tim,
Cooke Sam F.,
Avila Jesús,
Lucas José J.,
Giese Karl Peter,
Stephenson John,
Lovestone Simon
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05245.x
Subject(s) - long term potentiation , gsk 3 , gsk3b , synaptic plasticity , glycogen synthase , neuroscience , phosphorylation , retrograde signaling , kinase , dentate gyrus , biology , microbiology and biotechnology , chemistry , hippocampal formation , signal transduction , biochemistry , receptor
Glycogen synthase kinase‐3 (GSK‐3) is a serine/threonine kinase regulating diverse cellular functions including metabolism, transcription and cell survival. Numerous intracellular signalling pathways converge on GSK‐3 and regulate its activity via inhibitory serine‐phosphorylation. Recently, GSK‐3 has been involved in learning and memory and in neurodegeneration. Here, we present evidence that implicates GSK‐3 in synaptic plasticity. We show that phosphorylation at the inhibitory Ser9 site on GSK‐3β is increased upon induction of long‐term potentiation (LTP) in both hippocampal subregions CA1 and the dentate gyrus (DG) in vivo . The increase in inhibitory GSK‐3β phosphorylation is robust and persists for at least one hour postinduction. Furthermore, we find that LTP is impaired in transgenic mice conditionally overexpressing GSK‐3β. The LTP deficits can be attenuated/rescued by chronic treatment with lithium, a GSK‐3 inhibitor. These results suggest that the inhibition of GSK‐3 facilitates the induction of LTP and this might explain some of the negative effects of GSK‐3 on learning and memory. It follows that this role of GSK‐3β in LTP might underlie some of the cognitive dysfunction in diseases where GSK‐3 dysfunction has been implicated, including Alzheimer's and other dementias.