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Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
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Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
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Journal Article
Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
2021
Overview
Mounting evidence implicates dysfunctional GABA
A
R-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 GABA
A
R 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Diazepam
/ Down Syndrome - drug therapy
/ EEG
/ Electrophysiological Phenomena - drug effects
/ Female
/ Humanities and Social Sciences
/ Long-Term Potentiation - drug effects
/ Male
/ Maze Learning - drug effects
/ Memory Disorders - drug therapy
/ Mice
/ Neuronal Plasticity - drug effects
/ Science
/ Seizures
/ Seizures - chemically induced
