Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety.

Collapse authors list.
Sato, Daiki X ORCID: 0000-0002-9527-8253, Inoue, Yukiko U, Kuga, Nahoko, Hattori, Satoko, Nomoto, Kensaku ORCID: 0000-0003-2953-4594, Morimoto, Yuki, Sala, Giovanni ORCID: 0000-0002-1589-3759, Hagihara, Hideo, Kikusui, Takefumi, Sasaki, Takuya et al (show 4 more authors) (2022) Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety. iScience, 25 (8). 104800-.

Access the full-text of this item by clicking on the Open Access link.

Official URL: http://dx.doi.org/10.1016/j.isci.2022.104800

Abstract

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1 Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

Item Type:	Article
Uncontrolled Keywords:	Behavior genetics, Evolutionary biology, Molecular Genetics, Molecular mechanism of behavior
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Population Health
Depositing User:	Symplectic Admin
Date Deposited:	09 Feb 2023 12:32
Last Modified:	15 Mar 2024 12:23
DOI:	10.1016/j.isci.2022.104800
Open Access URL:	https://www.sciencedirect.com/science/article/pii/...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3168317