Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala

Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase...

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Autores principales:	Aniruddha Das, Monica Dines, Jessica M. Alapin, Raphael Lamprecht
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19cb94cb09fd48dd8843c432138bdd00
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spelling	oai:doaj.org-article:19cb94cb09fd48dd8843c432138bdd002021-12-02T11:53:00ZAffecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala10.1038/s41598-017-13674-92045-2322https://doaj.org/article/19cb94cb09fd48dd8843c432138bdd002017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13674-9https://doaj.org/toc/2045-2322Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase (PAK) are involved in such key neuronal functions. Here we show that optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation. Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes before fear conditioning enhanced long-term but not short-term fear memory formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity during fear conditioning constrains the formation of fear memory in LA. Thus, Rac GTPase and PAK proteins may serve as targets for treatment of fear and anxiety disorders.Aniruddha DasMonica DinesJessica M. AlapinRaphael LamprechtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
description	Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase (PAK) are involved in such key neuronal functions. Here we show that optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation. Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes before fear conditioning enhanced long-term but not short-term fear memory formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity during fear conditioning constrains the formation of fear memory in LA. Thus, Rac GTPase and PAK proteins may serve as targets for treatment of fear and anxiety disorders.
format	article
author	Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht
author_facet	Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht
author_sort	Aniruddha Das
title	Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
title_short	Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
title_full	Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
title_fullStr	Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
title_full_unstemmed	Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
title_sort	affecting long-term fear memory formation through optical control of rac1 gtpase and pak activity in lateral amygdala
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/19cb94cb09fd48dd8843c432138bdd00
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Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala

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