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Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory

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Cite this article as: eLife 2020;9:e61036 doi: 10.7554/eLife.61036

Abstract

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms remain poorly understood. RNAseq from BLApn identified changes in multiple candidate learning-related transcripts including the expected immediate early gene Fos and Stk11, a master kinase of the AMP-related kinase pathway with important roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 in BLApn blocked memory prior to training, but not following it and increased neuronal excitability. Conversely, BLApn had reduced excitability following CTA. BLApn knockout of a second learning-related gene, Fos, also increased excitability and impaired learning. Independently increasing BLApn excitability chemogenetically during CTA also impaired memory. STK11 and C-FOS activation were independent of one another. These data suggest key roles for Stk11 and Fos in CTA long-term memory formation, dependent at least partly through convergent action on BLApn intrinsic excitability.

Data availability

Sequencing data was uploaded to GEO (accession number: GSE138522).

The following data sets were generated

Article and author information

Author details

  1. David Levitan

    Biology, Brandeis University, Waltham, United States
    For correspondence
    levitand@brandeis.edu
    Competing interests
    No competing interests declared.
  2. Chenghao Liu

    Biology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  3. Tracy Yang

    Biology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2437-9257
  4. Yasuyuki Shima

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  5. Jian-You Lin

    Psychology, Volen Center for Complex Systems, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  6. Joseph Wachutka

    Psychology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  7. Yasmin Marrero

    Psychology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  8. Ramin Ali Marandi Ghoddousi

    Biology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  9. Eduardo da Veiga Beltrame

    Psychology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  10. Troy A Richter

    Biology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
  11. Donald B Katz

    Department Of Psychology, Brandeis University, Waltham, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8444-6063
  12. Sacha B Nelson

    Department of Biology, Volen Center for Complex Systems, Brandeis University, Waltham, United States
    For correspondence
    nelson@brandeis.edu
    Competing interests
    Sacha B Nelson, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0108-8599

Funding

National Institute on Deafness and Other Communication Disorders (DC006666)

  • Donald B Katz

National Institute of Neurological Disorders and Stroke (NS109916)

  • Sacha B Nelson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were approved by the Brandeis University Institutional Animal Care and Use Committee (IACUC, Protocol #20002) in accordance with NIH guidelines.

Reviewing Editor

  1. Mary Kay Lobo, University of Maryland, United States

Publication history

  1. Received: July 14, 2020
  2. Accepted: August 4, 2020
  3. Accepted Manuscript published: August 11, 2020 (version 1)
  4. Version of Record published: August 24, 2020 (version 2)

Copyright

© 2020, Levitan 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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