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-subjects design, delineating patterns of transcriptional change that are comprehensive and reproducible. We have previously reported that within 1 day of long-term sensitization training there is a widespread transcriptional response involving robust changes in over 5% of tested transcripts (1,252 of ∼22k; Conte, 2017). Within 1 week, however, memory strength fades and nearly all transcriptional changes relapse to baseline (Perez, 2018). Here we report microarray analysis (N = 16) of transcriptional changes 5 days post-learning, a time-point when memory strength has weakened but is still robust. Remarkably, we find 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.Significance Statement This project characterizes the transcriptional state accompanying a partially-forgotten long-term memory in Aplysia, showing that most transcriptional changes induced during learning fade before forgetting is complete. These results raise interesting questions about the interrelationships between transcriptional, neuronal, and behavioral change.