RT Journal Article SR Electronic T1 Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting is Due to Retrieval Failure JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0313-19.2020 DO 10.1523/ENEURO.0313-19.2020 VO 7 IS 6 A1 Tania Rosiles A1 Melissa Nguyen A1 Monica Duron A1 Annette Garcia A1 George Garcia A1 Hannah Gordon A1 Lorena Juarez A1 Irina E. Calin-Jageman A1 Robert J. Calin-Jageman YR 2020 UL http://www.eneuro.org/content/7/6/ENEURO.0313-19.2020.abstract AB There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible because of retrieval failure. These different accounts of forgetting lead to different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is because of decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is because of retrieval failure, then savings should be mechanistically distinct from encoding. In this registered report, we conducted a preregistered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 d after training), a forgotten memory (8 d after training), and a savings memory (8 d after training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We found that the reactivation of sensitization during savings does not involve a substantial transcriptional response. Thus, savings is transcriptionally distinct relative to a newer (1-d-old) memory, with no coregulated transcripts, negligible similarity in regulation-ranked ordering of transcripts, and a negligible correlation in training-induced changes in gene expression (r = 0.04 95% confidence interval (CI) [–0.12, 0.20]). Overall, our results suggest that forgetting of sensitization memory represents retrieval failure.