Identification of plasticity-associated genes regulated by Pavlovian fear conditioning in the lateral amygdala.

摘要

Most recent studies aimed at defining the cellular and molecular mechanisms of Pavlovian fear conditioning have focused on protein kinase signaling pathways and the transcription factor cAMP-response element binding protein (CREB) that promote fear memory consolidation in the lateral nucleus of the amygdala (LA). Despite this progress, there still remains a paucity of information regarding the genes downstream of CREB that are required for long-term fear memory formation in the LA. We have adopted a strategy of using microarray technology to initially identify genes induced within the dentate gyrus following in vivo long-term potentiation (LTP) followed by analysis of whether these same genes are also regulated by fear conditioning within the LA. In the present study, we first identified 34 plasticity-associated genes that are induced within 30 min following LTP induction utilizing a combination of DNA microarray, qRT-PCR, and in situ hybridization. To determine whether these genes are also induced in the LA following Pavlovian fear conditioning, we next exposed rats to an auditory fear conditioning protocol or to control conditions that do not support fear learning followed by qRT-PCR on mRNA from microdissected LA samples. Finally, we asked whether identified genes induced by fear learning in the LA are downstream of the extracellular-regulated kinase/mitogen-activated protein kinase signaling cascade. Collectively, our findings reveal a comprehensive list of genes that represent the first wave of transcription following both LTP induction and fear conditioning that largely belong to a class of genes referred to as 'neuronal activity dependent genes' that are likely calcium, extracellular-regulated kinase/mitogen-activated protein kinase, and CREB-dependent.