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

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 <i>Fos</i> and <i>Stk11</i>, 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 <i>Stk11</i> 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, <i>Fos</i>, 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 <i>Stk11</i> and <i>Fos</i> in CTA long-term memory formation, dependent at least partly through convergent action on BLApn intrinsic excitability.