Glycogen synthase kinase-3 inhibition is integral to long-term potentiation

Claudie Hooper, Vladimir Markevich, Florian Plattner, Richard Killick, Emma Schofield, Tobias Engel, Felix Hernandez, Brian Anderton, Kobi Rosenblum, Tim Bliss, Sam F. Cooke, Jesús Avila, José J. Lucas, Karl Peter Giese, John Stephenson, Simon Lovestone

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalEuropean Journal of Neuroscience
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Alzheimer's disease
  • GSK-3
  • Mice
  • Notch
  • Wnt

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hooper, C., Markevich, V., Plattner, F., Killick, R., Schofield, E., Engel, T., Hernandez, F., Anderton, B., Rosenblum, K., Bliss, T., Cooke, S. F., Avila, J., Lucas, J. J., Giese, K. P., Stephenson, J., & Lovestone, S. (2007). Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. European Journal of Neuroscience, 25(1), 81-86. https://doi.org/10.1111/j.1460-9568.2006.05245.x