Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

Abstract Rho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overco...

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Autores principales:	Audrey J. Weber, Ashley B. Adamson, Kelsey M. Greathouse, Julia P. Andrade, Cameron D. Freeman, Jung Vin Seo, Rosaria J. Rae, Courtney K. Walker, Jeremy H. Herskowitz
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	ROCK2 Rho kinase Dendritic spine Hippocampus Prefrontal cortex Amygdala Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/4e3a6b68158042169c1a16a3a1c2db46
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spelling	oai:doaj.org-article:4e3a6b68158042169c1a16a3a1c2db462021-11-21T12:41:53ZConditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons10.1186/s13041-021-00878-41756-6606https://doaj.org/article/4e3a6b68158042169c1a16a3a1c2db462021-11-01T00:00:00Zhttps://doi.org/10.1186/s13041-021-00878-4https://doaj.org/toc/1756-6606Abstract Rho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.Audrey J. WeberAshley B. AdamsonKelsey M. GreathouseJulia P. AndradeCameron D. FreemanJung Vin SeoRosaria J. RaeCourtney K. WalkerJeremy H. HerskowitzBMCarticleROCK2Rho kinaseDendritic spineHippocampusPrefrontal cortexAmygdalaNeurology. Diseases of the nervous systemRC346-429ENMolecular Brain, Vol 14, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ROCK2 Rho kinase Dendritic spine Hippocampus Prefrontal cortex Amygdala Neurology. Diseases of the nervous system RC346-429
spellingShingle	ROCK2 Rho kinase Dendritic spine Hippocampus Prefrontal cortex Amygdala Neurology. Diseases of the nervous system RC346-429 Audrey J. Weber Ashley B. Adamson Kelsey M. Greathouse Julia P. Andrade Cameron D. Freeman Jung Vin Seo Rosaria J. Rae Courtney K. Walker Jeremy H. Herskowitz Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
description	Abstract Rho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.
format	article
author	Audrey J. Weber Ashley B. Adamson Kelsey M. Greathouse Julia P. Andrade Cameron D. Freeman Jung Vin Seo Rosaria J. Rae Courtney K. Walker Jeremy H. Herskowitz
author_facet	Audrey J. Weber Ashley B. Adamson Kelsey M. Greathouse Julia P. Andrade Cameron D. Freeman Jung Vin Seo Rosaria J. Rae Courtney K. Walker Jeremy H. Herskowitz
author_sort	Audrey J. Weber
title	Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
title_short	Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
title_full	Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
title_fullStr	Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
title_full_unstemmed	Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
title_sort	conditional deletion of rock2 induces anxiety-like behaviors and alters dendritic spine density and morphology on ca1 pyramidal neurons
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4e3a6b68158042169c1a16a3a1c2db46
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Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

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