Enhanced Sensitization Training in Aplysia Produces a Focused, Distinctive Set of Transcriptional Changes that Mostly Decays as Memory is Maintained
Year: 2026
Type: preprint
Abstract: Forgetting remains a key puzzle in the neurobiology of memory. One mysterious aspect of forgetting is its selectivity: most long-term memories are forgotten, becoming progressively less likely to be recalled, but extensive training can produce long-term memories that are readily expressed for a lifetime. What are the molecular mechanisms through which training forestalls forgetting? To explore this issue, we leveraged a well-documented training effect in long-term sensitization in Aplysia californica: a 1-day training protocol (standard) produces sensitization that is forgotten within 7 days, whereas 4-days of training (enhanced) produces sensitization that is durably expressed. Here we confirm that enhanced sensitization training produces an enduring form of sensitization, with only subtle levels of forgetting for up to 11 days after training. We then used microarray and qPCR to characterize the transcriptional changes occurring 1, 5, and 11 days after enhanced sensitization training. We find that enhanced sensitization sustains only about 6% of the transcriptional changes induced by standard training, with many memory-linked transcripts showing no (ApCREB1) or significantly weaker (ApEgr) regulation with additional training. Enhanced training also produces distinct activation of about 20 transcripts (relative to standard training), including up-regulation of putative homologs of genes related to synaptic plasticity (HINT1) and axon maintenance (zig-4). Surprisingly, most of the transcriptional changes initially accompanying enhanced training fade rapidly, with the typical training effect at day 1 declining to 45% as strong by day 5 and then 28% as strong by day 11. This decay is not complete, and we find sustained regulation of several transcripts, including some also persistently regulated by enhanced training (e.g. FMRFa and a putative GRIK1 homolog). Overall, our results suggest that additional training produces a weaker but somewhat distinctive transcriptional response, most of which fades well before memory expression.
Source: PsyArXiv (OSF Preprints)
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221912209