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.

Metrics

  • 2,193
    Page views
  • 269
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Neuroscience
    Movitz Lenninger, Mikael Skoglund ... Arvind Kumar
    Research Article Updated

    According to the efficient coding hypothesis, sensory neurons are adapted to provide maximal information about the environment, given some biophysical constraints. In early visual areas, stimulus-induced modulations of neural activity (or tunings) are predominantly single-peaked. However, periodic tuning, as exhibited by grid cells, has been linked to a significant increase in decoding performance. Does this imply that the tuning curves in early visual areas are sub-optimal? We argue that the time scale at which neurons encode information is imperative to understand the advantages of single-peaked and periodic tuning curves, respectively. Here, we show that the possibility of catastrophic (large) errors creates a trade-off between decoding time and decoding ability. We investigate how decoding time and stimulus dimensionality affect the optimal shape of tuning curves for removing catastrophic errors. In particular, we focus on the spatial periods of the tuning curves for a class of circular tuning curves. We show an overall trend for minimal decoding time to increase with increasing Fisher information, implying a trade-off between accuracy and speed. This trade-off is reinforced whenever the stimulus dimensionality is high, or there is ongoing activity. Thus, given constraints on processing speed, we present normative arguments for the existence of the single-peaked tuning organization observed in early visual areas.

    1. Genetics and Genomics
    2. Neuroscience
    Timothy Wu, Jennifer M Deger ... Joshua M Shulman
    Research Article Updated

    Aging is a major risk factor for Alzheimer’s disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in Drosophila with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- and aging-induced gene expression strongly overlap (93%), they differ in the affected cell types. In contrast to the broad impact of aging, tau-triggered changes are strongly polarized to excitatory neurons and glia. Further, tau can either activate or suppress innate immune gene expression signatures in a cell-type-specific manner. Integration of cellular abundance and gene expression pinpoints nuclear factor kappa B signaling in neurons as a marker for cellular vulnerability. We also highlight the conservation of cell-type-specific transcriptional patterns between Drosophila and human postmortem brain tissue. Overall, our results create a resource for dissection of dynamic, age-dependent gene expression changes at cellular resolution in a genetically tractable model of tauopathy.