Transcriptional Changes Fade Prior to Long-Term Memory for Sensitization of the Aplysia Siphon-Withdrawal Reflex

Forming a long-term memory requires changes in neuronal transcription. What happens, though, as the memory is forgotten? And how does the transcriptional state relate to the maintenance and recall of the long-term memory? To answer these questions, we have been systematically tracing the time course of transcriptional changes evoked by long-term sensitization in the marine mollusk Aplysia californica Our approach captures transcriptional changes in neurons of known behavioral relevance using a within-subject design, delineating patterns of transcriptional change that are comprehensive and reproducible. We have previously reported that within 1 d of long-term sensitization training, there is a widespread transcriptional response involving robust changes in over 5% of tested transcripts (1,198 of ∼22 k; Conte et al., 2017). Within 1 week, however, memory strength fades, and nearly all transcriptional changes relapse to baseline ( Perez et al., 2018). Here we report microarray analysis (N = 16) of transcriptional changes 5 d postlearning, a time point when memory strength has weakened but is still robust. Remarkably, we found that at this intermediate behavioral stage, nearly all transcriptional changes have fully decayed, even in subsets of animals that have shown very little forgetting. Thus, most transcriptional changes seem to decay more rapidly than memory expression. We discuss several possible ways that memory expression could become decoupled from detectable transcriptional regulation.