Preferential Arc transcription at rest in the active ensemble during associative learning

Abstract

Information processing in the central nervous system (CNS) during periods of rest is crucial for lasting memories but the precise off-line neuronal population activity that contributes to long-term memory formation remains unclear. This pattern of neuronal activity during rest triggers transcription of immediate early genes such as activity regulated cytoskeletal gene (Arc). We compared the active neuronal population in the lateral amygdala of C57BL/6J mice during fear conditioning and rest periods using a large scale imaging technique, Arc cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH). We found that the neuronal population transcribing Arc during fear conditioning was more similar to that the population transcribing Arc after fear conditioning than before fear conditioning. The overlapping population was larger in conditioned mice that acquired associative memory than in unshocked mice and in latent inhibited mice that received shocks but did not form associative memory. Moreover, these results were confirmed using Arc/Homer 1a catFISH. Our findings indicate that Arc is preferentially transcribed in neurons that are active during fear conditioning after associative learning. This preferential transcription may contribute to the formation of long-lasting memory.