Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory
- Brandeis University, United States
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).
Article and author information
Author details
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.
Reviewing Editor
- Mary Kay Lobo, University of Maryland, United States
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.
Version history
- Received: July 14, 2020
- Accepted: August 4, 2020
- Accepted Manuscript published: August 11, 2020 (version 1)
- 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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Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory
eLife 9:e61036.
https://doi.org/10.7554/eLife.61036
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