Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory

P21-activated kinase 3 (PAK3) gene mutations are linked to several neurodevelopmental disorders, but the underlying mechanisms remain unclear. In this study, we used a tetracycline-inducible system to control the expression of a mutant PAK3 (mPAK3) protein in immediate early gene, namely cFos, posit...

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Autores principales:	Susan Zhou, Zhengping Jia
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	p21-activated kinase tetracycline-inducible system cFos positive cells social recognition memory Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0285c174aed64877b54cc913a28d88c5
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spelling	oai:doaj.org-article:0285c174aed64877b54cc913a28d88c52021-11-25T17:10:23ZDisruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory10.3390/cells101130102073-4409https://doaj.org/article/0285c174aed64877b54cc913a28d88c52021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3010https://doaj.org/toc/2073-4409P21-activated kinase 3 (PAK3) gene mutations are linked to several neurodevelopmental disorders, but the underlying mechanisms remain unclear. In this study, we used a tetracycline-inducible system to control the expression of a mutant PAK3 (mPAK3) protein in immediate early gene, namely cFos, positive cells to disrupt PAK signaling, specifically in cells activated by social interaction in transgenic mice. We show that the expression of mPAK3-GFP proteins was in cFos-expressing excitatory and inhibitory neurons in various brain regions, such as the cortex and hippocampus, commonly activated during learning and memory. Basal expression of mPAK3-GFP proteins in cFos-positive cells resulted in social recognition memory deficits in the three-chamber social interaction test, without affecting locomotor activity or other forms of memory. The social memory deficit was rescued by doxycycline to halt the mPAK3-GFP transgene expression. In addition, we show that the expression of mPAK3-GFP proteins in a subset of cFos-positive cells, induced by an antecedent short social interaction, termed social pairing, was sufficient to impair social recognition memory. These results indicate that normal PAK signaling in cFos-positive cells activated during social interaction is critical for social memory.Susan ZhouZhengping JiaMDPI AGarticlep21-activated kinasetetracycline-inducible systemcFos positive cellssocial recognition memoryBiology (General)QH301-705.5ENCells, Vol 10, Iss 3010, p 3010 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	p21-activated kinase tetracycline-inducible system cFos positive cells social recognition memory Biology (General) QH301-705.5
spellingShingle	p21-activated kinase tetracycline-inducible system cFos positive cells social recognition memory Biology (General) QH301-705.5 Susan Zhou Zhengping Jia Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
description	P21-activated kinase 3 (PAK3) gene mutations are linked to several neurodevelopmental disorders, but the underlying mechanisms remain unclear. In this study, we used a tetracycline-inducible system to control the expression of a mutant PAK3 (mPAK3) protein in immediate early gene, namely cFos, positive cells to disrupt PAK signaling, specifically in cells activated by social interaction in transgenic mice. We show that the expression of mPAK3-GFP proteins was in cFos-expressing excitatory and inhibitory neurons in various brain regions, such as the cortex and hippocampus, commonly activated during learning and memory. Basal expression of mPAK3-GFP proteins in cFos-positive cells resulted in social recognition memory deficits in the three-chamber social interaction test, without affecting locomotor activity or other forms of memory. The social memory deficit was rescued by doxycycline to halt the mPAK3-GFP transgene expression. In addition, we show that the expression of mPAK3-GFP proteins in a subset of cFos-positive cells, induced by an antecedent short social interaction, termed social pairing, was sufficient to impair social recognition memory. These results indicate that normal PAK signaling in cFos-positive cells activated during social interaction is critical for social memory.
format	article
author	Susan Zhou Zhengping Jia
author_facet	Susan Zhou Zhengping Jia
author_sort	Susan Zhou
title	Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
title_short	Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
title_full	Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
title_fullStr	Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
title_full_unstemmed	Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
title_sort	disruption of pak3 signaling in social interaction induced cfos positive cells impairs social recognition memory
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0285c174aed64877b54cc913a28d88c5
work_keys_str_mv	AT susanzhou disruptionofpak3signalinginsocialinteractioninducedcfospositivecellsimpairssocialrecognitionmemory AT zhengpingjia disruptionofpak3signalinginsocialinteractioninducedcfospositivecellsimpairssocialrecognitionmemory
_version_	1718412630021898240

Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory

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