Specific Role for GSK3α in Limiting Long-Term Potentiation in CA1 Pyramidal Neurons of Adult Mouse Hippocampus

Aeen Ebrahim Amini; Tsukiko Miyata; Gang Lei; Fuzi Jin; Elizabeth Rubie; Clarrisa A Bradley; James R Woodgett; Graham L Collingridge; John Georgiou

doi:10.3389/fnmol.2022.852171

Specific Role for GSK3α in Limiting Long-Term Potentiation in CA1 Pyramidal Neurons of Adult Mouse Hippocampus

Front Mol Neurosci. 2022 Jun 17:15:852171. doi: 10.3389/fnmol.2022.852171. eCollection 2022.

Authors

Aeen Ebrahim Amini^{1

2}, Tsukiko Miyata^{1

3}, Gang Lei¹, Fuzi Jin¹, Elizabeth Rubie¹, Clarrisa A Bradley⁴, James R Woodgett^{1

3}, Graham L Collingridge^{1

2

5}, John Georgiou¹

Affiliations

¹ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
² Department of Physiology, University of Toronto, Toronto, ON, Canada.
³ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
⁴ Neurosciences and Mental Health Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
⁵ TANZ Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

Abstract

Glycogen synthase kinase-3 (GSK3) mediates phosphorylation of several hundred proteins, and its aberrant activity is associated with an array of prevalent disorders. The two paralogs, GSK3α and GSK3β, are expressed ubiquitously and fulfill common as well as unique tasks throughout the body. In the CNS, it is established that GSK3 is involved in synaptic plasticity. However, the relative roles of GSK3 paralogs in synaptic plasticity remains controversial. Here, we used hippocampal slices obtained from adult mice to determine the role of each paralog in CA3-CA1 long-term potentiation (LTP) of synaptic transmission, a form of plasticity critically required in learning and memory. Conditional Camk2a Cre-driven neuronal deletion of the Gsk3a gene, but not Gsk3b, resulted in enhanced LTP. There were no changes in basal synaptic function in either of the paralog-specific knockouts, including several measures of presynaptic function. Therefore, GSK3α has a specific role in serving to limit LTP in adult CA1, a postsynaptic function that is not compensated by GSK3β.

Keywords: CA3-CA1 synapses; GSK-3 (glycogen synthase kinase 3); GSK-3α; GSK-3β; LTP (long term potentiation); conditional knock out mice; synaptic function; synaptic plasticity.