TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala

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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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Ke-Xin Li

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Mu He

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Wenlei Ye

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4694-1493
Jeffrey Simms

Gladstone Institute of Neurological Disease, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Michael Gill

Gladstone Institute of Neurological Disease, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Xuaner Xiang

Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Yuh Nung Jan

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1367-6299
Lily Yeh Jan

Department of Physiology, University of California, San Francisco, San Francisco, United States

For correspondence
Lily.Jan@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3938-8498

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.

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.

Copyright

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.