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

  1. Ke-Xin Li
  2. Mu He
  3. Wenlei Ye
  4. Jeffrey Simms
  5. Michael Gill
  6. Xuaner Xiang
  7. Yuh Nung Jan
  8. Lily Yeh Jan  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Gladstone Institute of Neurological Disease, United States

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

  1. 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.
  2. Mu He

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wenlei Ye

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4694-1493
  4. Jeffrey Simms

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Gill

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. 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.
  7. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1367-6299
  8. 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.
    ORCID icon "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.

Reviewing Editor

  1. Lisa M Monteggia, Vanderbilt University, United States

Publication history

  1. Received: March 24, 2019
  2. Accepted: September 4, 2019
  3. Accepted Manuscript published: September 4, 2019 (version 1)
  4. 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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  1. Ke-Xin Li
  2. Mu He
  3. Wenlei Ye
  4. Jeffrey Simms
  5. Michael Gill
  6. Xuaner Xiang
  7. Yuh Nung Jan
  8. Lily Yeh Jan
(2019)
TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala
eLife 8:e47106.
https://doi.org/10.7554/eLife.47106
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