Sex-Specific Stress-Related Behavioral Phenotypes and Central Amygdala Dysfunction in a Mouse Model of 16p11.2 Microdeletion

Giovanniello, Jacqueline, Ahrens, Sandra, Yu, Kai, Li, Bo (June 2021) Sex-Specific Stress-Related Behavioral Phenotypes and Central Amygdala Dysfunction in a Mouse Model of 16p11.2 Microdeletion. Biological Psychiatry Global Open Science, 1 (1). pp. 59-69. ISSN 2667-1743

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Abstract

Background: Substantial evidence indicates that a microdeletion on human chromosome 16p11.2 is linked to neurodevelopmental disorders, including autism spectrum disorder (ASD). Carriers of this deletion show divergent symptoms besides the core features of autism spectrum disorder, such as anxiety and emotional symptoms. The neural mechanisms underlying these symptoms are poorly understood. Methods: We used mice heterozygous for a deletion allele of the genomic region corresponding to the human 16p11.2 microdeletion locus (i.e., 16p11.2 del/+ mice) and their sex-matched wild-type littermates for the study and examined their anxiety-related behaviors, auditory perception, and central amygdala circuit function using behavioral, circuit tracing, and electrophysiological techniques. Results: Mice heterozygous for a deletion allele of the genomic region corresponding to the human 16p11.2 microdeletion locus (i.e., 16p11.2 del/+ mice) had sex-specific anxiety-related behavioral and neural circuit changes. Specifically, we found that female, but not male, 16p11.2 del/+ mice showed enhanced fear generalization-a hallmark of anxiety disorders-after auditory fear conditioning and displayed increased anxiety-like behaviors after physical restraint stress. Notably, such sex-specific behavioral changes were paralleled by an increase in activity in central amygdala neurons projecting to the globus pallidus in female, but not male, 16p11.2 del/+ mice. Conclusions: Together, these results reveal female-specific anxiety phenotypes related to 16p11.2 microdeletion syndrome and a potential underlying neural circuit mechanism. Our study therefore identifies previously underappreciated sex-specific behavioral and neural changes in a genetic model of 16p11.2 microdeletion syndrome and highlights the importance of investigating female-specific aspects of this syndrome for targeted treatment strategies.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > amygdala organism description > animal behavior > sex differences organism description > animal behavior > stress
CSHL Authors:	Ahrens, Sandra Yu, Kai Giovanniello, Jacqueline Li, Bo
Communities:	CSHL labs > Li lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	June 2021
Date Deposited:	08 Jul 2021 20:57
Last Modified:	29 Feb 2024 19:56
PMCID:	PMC9616311
URI:	https://repository.cshl.edu/id/eprint/40262

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