@article {RosilesENEURO.0313-19.2020, author = {Tania Rosiles and Melissa Nguyen and Monica Duron and Annette Garcia and George Garcia and Hannah Gordon and Lorena Juarez and Irina E. Calin-Jageman and Robert J. Calin-Jageman}, title = {Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting Is Due to Retrieval Failure}, elocation-id = {ENEURO.0313-19.2020}, year = {2020}, doi = {10.1523/ENEURO.0313-19.2020}, publisher = {Society for Neuroscience}, abstract = {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 due to 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 due to decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval failure, then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day after training), a forgotten memory (8 days after training), and a savings memory (8 days 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 re-activation of sensitization during savings does not involve a substantial transcriptional response. Thus, savings is transcriptionally distinct relative to a newer (1-day old) memory, with no co-regulated transcripts, negligible similarity in regulation-ranked ordering of transcripts, and a negligible correlation in training-induced changes in gene expression (r = .04 95\% CI [-.12, .20]). Overall, our results suggest that forgetting of sensitization memory represents retrieval failure.Significance Statement Understanding the nature of forgetting is important because both excessive and insufficient forgetting are related to profound disruptions of mental health. This registered report provides molecular data indicating that forgetting of long-term sensitization in Aplysia represents retrieval failure, contributing new evidence towards resolving a long-standing debate over the neural mechanisms of forgetting.}, URL = {https://www.eneuro.org/content/early/2020/09/14/ENEURO.0313-19.2020}, eprint = {https://www.eneuro.org/content/early/2020/09/14/ENEURO.0313-19.2020.full.pdf}, journal = {eNeuro} }