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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.


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.

SUBMITTER: Levitan D 

PROVIDER: S-EPMC7445010 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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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.

Levitan David D   Liu Chenghao C   Yang Tracy T   Shima Yasuyuki Y   Lin Jian-You JY   Wachutka Joseph J   Marrero Yasmin Y   Ali Marandi Ghoddousi Ramin R   Veiga Beltrame Eduardo da ED   Richter Troy A TA   Katz Donald B DB   Nelson Sacha B SB  

eLife 20200811


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 implicat  ...[more]

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