Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome

Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an...

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Autores principales:	Daniella B. Victorino, Daniel J. L. L. Pinheiro, Jonah J. Scott-McKean, Sarah Barker, Melissa R. Stasko, Jean Faber, Carla A. Scorza, Alberto C. S. Costa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5901e46d3ede478a8d1e006e2f931c75
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spelling	oai:doaj.org-article:5901e46d3ede478a8d1e006e2f931c752021-12-02T14:49:26ZAtypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome10.1038/s41598-021-89011-y2045-2322https://doaj.org/article/5901e46d3ede478a8d1e006e2f931c752021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89011-yhttps://doaj.org/toc/2045-2322Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.Daniella B. VictorinoDaniel J. L. L. PinheiroJonah J. Scott-McKeanSarah BarkerMelissa R. StaskoJean FaberCarla A. ScorzaAlberto C. S. CostaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
description	Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.
format	article
author	Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa
author_facet	Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa
author_sort	Daniella B. Victorino
title	Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
title_short	Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
title_full	Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
title_fullStr	Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
title_full_unstemmed	Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
title_sort	atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of down syndrome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5901e46d3ede478a8d1e006e2f931c75
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Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome

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