TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala
Abstract
TMEM16B (ANO2) is the Ca2+-activated chloride channel expressed in multiple brain regions, including the amygdala. Here we report that Ano2 knockout mice exhibit impaired anxiety-related behaviors and context-independent fear memory, thus implicating TMEM16B in anxiety modulation. We found that TMEM16B is expressed in somatostatin-positive (SOM+) GABAergic neurons of the central lateral amygdala (CeL), and its activity modulates action potential duration and inhibitory postsynaptic current (IPSC). We further provide evidence for TMEM16B actions not only in the soma but also in the presynaptic nerve terminals of GABAergic neurons. Our study reveals an intriguing role for TMEM16B in context-independent but not context-dependent fear memory, and supports the notion that dysfunction of the amygdala contributes to anxiety-related behaviors.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institute for Health Research (RO1 NS069229)
- Lily Yeh Jan
Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD089639)
- Mu He
Howard Hughes Medical Institute
- Yuh Nung Jan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lisa M Monteggia, Vanderbilt University, United States
Ethics
Animal experimentation: The use and care of the mice complied with the guidelines of the Institutional Animal Care and Use Committee of UCSF (IACUC protocol AN181236), in accordance with the US National Institute of Health guidelines.
Version history
- Received: March 24, 2019
- Accepted: September 4, 2019
- Accepted Manuscript published: September 4, 2019 (version 1)
- Version of Record published: September 16, 2019 (version 2)
Copyright
© 2019, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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