Transcriptional Changes Before and After Forgetting of a Long-Term Sensitization Memory in Aplysia californica

Abstract

This is a pre-print of a paper now published in Neurobiology of Learning and Memory: https://doi.org/10.1016/j.nlm.2018.09.007 Most long-term memories are forgotten, becoming progressively less likely to be recalled. Still, some memory fragments may persist beyond forgetting, as savings memory (easier relearning) can persist long after recall has become impossible. What happens to a memory trace during forgetting that makes it inaccessible for recall and yet still effective to spark easier re-learning? We are addressing this question by tracking the transcriptional changes that accompany learning and then forgetting of a long-term sensitization memory in the tail-elicited siphon withdrawal reflex of Aplysia californica. First, we tracked savings memory. We found that even though recall of sensitization fades completely within 1 week of training, savings memory is still robustly expressed at 2 weeks post training. Next, we tracked the time-course of regulation of 11 transcripts we previously identified as potentially being regulated beyond the decay of recall. Remarkably, 3 transcripts still show strong regulation of expression 2 weeks after training and an additional 4 are regulated for at least 1 week. These long-lasting changes in gene expression always began early in the memory process, within 1 day of training. We present a synthesis of our results tracking gene expression changes accompanying sensitization and provide a testable model of how sensitization memory is forgotten.

pH dependence of C•A, G•A and A•A mismatches in the stem of precursor microRNA-31

“…These mismatched regions are thought to mediate important intermolecular interactions, including protein recognition [48][49][50][51][52][53][54] and define the global RNA structure [55][56][57][58]. Internal loops have also been shown to be important for RNA-mediated processes like ribozyme cleavage [59][60][61], RNA conformational changes [62][63][64], and RNA processing [65][66][67][68].…”

Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization inAplysia

“…Long-term sensitization requires changes in gene expression ( Sutton et al, 2001 ), and training produces a complex transcriptional cascade in neurons that contribute to the T-SWR (reviewed in Calin-Jageman et al, 2023 ). Interestingly, some learning-induced transcriptional changes seem likely to oppose sensitization.…”

Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization in Aplysia

“…Long-term sensi za on requires changes in gene expression (Su on et al, 2001), and training produces a complex transcrip onal cascade in neurons that contribute to the T-SWR (reviewed in Calin-Jageman et al, 2023). Interes ngly, some learning-induced transcrip onal changes seem likely to oppose sensi za on.…”