Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Kaneko, Megumi, Cheetham, Claire E., Lee, Yong-Seok, Silva, Alcino J., Stryker, Michael P. and Fox, Kevin Dyson ORCID: https://orcid.org/0000-0002-2563-112X 2010. Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex. Proceedings of the National Academy of Sciences of the United States of America 107 (44) , pp. 19026-19031. 10.1073/pnas.1013866107

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Abstract

Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras (H-ras(G12V)), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, H-ras(G12V) not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, H-ras(G12V) expression decreased baseline presynaptic release probability and enhanced presynaptically expressed long-term potentiation (LTP). H-ras(G12V) expression also accelerated the increase following MD in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	gain of function; monocular deprivation; mouse; ocular dominance; presynaptic long-term potentiation
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Funders:	MRC, NIMH Conte Center
Last Modified:	19 Oct 2022 10:20
URI:	https://orca.cardiff.ac.uk/id/eprint/24056

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