Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala

Abstract

Abstract RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala ( LA ) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNA s from the dissected neurons were subjected to microarray analysis. The levels of selected RNA s detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA . The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical‐ LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory‐related disorders. image We monitored gene expression after fear conditioning learning in thalamus‐lateral amygdala (LA) and cortex‐LA brain pathways. We detected genes that are specifically increased after fear learning and that encode proteins that function as regulators of protein synthesis, maturation and degradation in thalamus‐LA pathway and regulators of transcription in the cortex‐LA pathway. These findings provide insights into the molecular mechanisms involved in fear memory formation.