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

Elife. 2020 Aug 11:9: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.

Keywords: Stk11; basolateral amygdala; excitability; fos; memory; mouse; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Basolateral Nuclear Complex* / chemistry
  • Basolateral Nuclear Complex* / cytology
  • Basolateral Nuclear Complex* / metabolism
  • Conditioning, Classical / physiology*
  • Female
  • Gene Knockout Techniques
  • Male
  • Memory, Long-Term / physiology*
  • Mice
  • Neurons / chemistry
  • Neurons / metabolism
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Proto-Oncogene Proteins c-fos* / genetics
  • Proto-Oncogene Proteins c-fos* / metabolism
  • Taste / physiology

Substances

  • Fos protein, mouse
  • Proto-Oncogene Proteins c-fos
  • Protein Serine-Threonine Kinases
  • Stk11 protein, mouse
  • AMP-Activated Protein Kinases

Associated data

  • GEO/GSE138522