Savings memory is accompanied by transcriptional changes that persist beyond the decay of recall

Abstract

Most long-term memories are forgotten. What happens, then, to the changes in neuronal gene expression that were initially required to encode and maintain the memory? Here we show that the decay of recall for long-term sensitization memory in is accompanied both by a form of savings memory (easier relearning) and by persistent transcriptional regulation. A behavioral experiment ( = 14) shows that sensitization training produces a robust long-term sensitization memory, but that recall fades completely within 1 wk. This apparent forgetting, though, is belied by persistent savings memory, as we found that a weak reminder protocol reinstates a long-term sensitization memory only on the previously trained side of the body. Using microarray ( = 8 biological replicates), we found that transcriptional regulation largely decays along with recall. Of the transcripts known to be regulated 1 d after training, 98% (1172/1198) are no longer significantly regulated 7 d after training. Still, there is a small set of transcripts which remain strongly regulated even when recall is absent. Using qPCR ( = 11 additional biological replicates) we confirmed that these include the peptide transmitter FMRFamide, a transcript encoding a putative homolog of spectrin beta chain (Genbank: EB255259) , a transcript encoding a protein with a predicted EF-hand calcium-binding domain (Genbank: EB257711), and eight uncharacterized transcripts. To our knowledge, this is the first work to show that transcriptional changes evoked by learning can outlast recall. The small set of transcriptional changes that persist could mediate the rapid relearning of the memory (savings), or the decay of recall, or both, or neither.

The New Statistics for Neuroscience Majors: Thinking in Effect Sizes

“…The effect size is the 'difference of the difference', or the comparison of the two simple effects. Example from Perez et al (2018): In naive animals, the weak shock produced a 3% decrease in reflex responsiveness. In previously trained animals, the weak shock produced a 23% increase in reflex responsiveness.…”

“…We now obtain effect sizes of around 2.6 standard deviations. With much larger effect sizes we now use fewer animals (8-12/experiment) to obtain much more consistent results (Conte et al 2017;Perez et al 2018).…”

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

“…We have recently extended these findings by showing that transcriptional changes can also be detected after the decay of recall for a long-term memory (Perez, Patel, Rivota, Calin-jageman, & Calin-Jageman, 2018). Specifically, we used microarray and qPCR to identify changes in gene expression that accompany forgetting of a long-term sensitization memory in Aplysia californica.…”

“…This apparent forgetting, however, belies a persistent savings memory, as a brief re-training can produce a long-lasting re-expression of the sensitization memory (Perez et al, 2018).…”

“…This consisted of two moderate shocks (60Hz biphasic DC pulse for 2s at 20ma of constant current) applied to the midline of the tail with a 15-minute rest between the shocks. This protocol is strong enough to produce short-term sensitization in naïve animals, but not sufficient to produce long-term sensitization (Perez et al, 2018;Philips et al, 2006).…”