Privitera, Lucia, Morè, Lorenzo, Cooper, Daniel D., Richardson, Philippa, Tsogka, Marianthi, Hebenstreit, Daniel, Arthur, J. Simon C. and Frenguelli, Bruno G. (2020) Experience recruits MSK1 to expand the dynamic range of synapses and enhance cognition. The Journal of neuroscience : the official journal of the Society for Neuroscience, 40 (24). pp. 4644-4660. JN-RM-2765-19. doi:10.1523/JNEUROSCI.2765-19.2020 ISSN 1529-2401.

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Abstract

Experience powerfully influences neuronal function and cognitive performance, but the cellular and molecular events underlying the experience-dependent enhancement of mental ability have remained elusive. In particular, the mechanisms that couple the external environment to the genomic changes underpinning this improvement are unknown. To address this we have used male mice harbouring an inactivating mutation of mitogen- and stress-activated protein kinase 1 (MSK1), a BDNF-activated enzyme downstream of the MAPK pathway. We show that MSK1 is required for the full extent of experience-induced improvement of spatial memory, for the expansion of the dynamic range of synapses, exemplified by the enhancement of hippocampal LTP and LTD, and for the regulation of the majority of genes influenced by enrichment. In addition, and unexpectedly, we show that experience is associated with an MSK1-dependent downregulation of key MAPK and plasticity-related genes, notably of EGR1/Zif268 and Arc/Arg3.1, suggesting the establishment of a novel genomic landscape adapted to experience. By coupling experience to homeostatic changes in gene expression MSK1, represents a prime mechanism through which the external environment has an enduring influence on gene expression, synaptic function and cognition.

Item Type:	Journal Article
Subjects:	B Philosophy. Psychology. Religion > BF Psychology Q Science > QH Natural history Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Cell metabolism -- Regulation, Cellular control mechanisms , Cognition, Neurotrophic functions, Gene expression, Synapses
Journal or Publication Title:	The Journal of neuroscience : the official journal of the Society for Neuroscience
Publisher:	Society for Neuroscience
ISSN:	1529-2401
Official Date:	10 June 2020
Dates:	Date Event 10 June 2020 Published UNSPECIFIED Available 20 April 2020 Accepted
Volume:	40
Number:	24
Page Range:	pp. 4644-4660
Article Number:	JN-RM-2765-19
DOI:	10.1523/JNEUROSCI.2765-19.2020
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Copyright Holders:	Copyright © 2020 Privitera et al.
Date of first compliant deposit:	11 May 2020
Date of first compliant Open Access:	11 May 2020
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID BB/L00139X/1 [BBSRC] Biotechnology and Biological Sciences Research Council http://dx.doi.org/10.13039/501100000268 BB/M01116X/1 DDC [BBSRC] Biotechnology and Biological Sciences Research Council http://dx.doi.org/10.13039/501100000268 UNSPECIFIED WPH Charitable Trust http://dx.doi.org/10.13039/100012362 UNSPECIFIED Sylvia Waddilove Foundation UNSPECIFIED UNSPECIFIED Erasmus+ http://dx.doi.org/10.13039/501100010790

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