RT Journal Article SR Electronic T1 RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0038-18.2018 DO 10.1523/ENEURO.0038-18.2018 A1 Alexis Bédécarrats A1 Shanping Chen A1 Kaycey Pearce A1 Diancai Cai A1 David L. Glanzman YR 2018 UL http://www.eneuro.org/content/early/2018/05/14/ENEURO.0038-18.2018.abstract AB The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naïve animals. Thus, the behavioral, and a subset of the cellular, modifications characteristic of a form of nonassociative long-term memory in Aplysia can be transferred by RNA. These results indicate that RNA is sufficient to generate an engram for long-term sensitization in Aplysia and are consistent with the hypothesis that RNA-induced epigenetic changes underlie memory storage in Aplysia.Significance Statement It is generally accepted that long-term memory (LTM) is encoded as alterations in synaptic strength. An alternative model, however, proposes that LTM is encoded by epigenetic changes. Non-coding RNAs can mediate epigenetic modifications. Therefore, RNA from a trained animal might be capable of producing learning-like behavioral change in an untrained animal. Here, it is demonstrated that the memory for long-term sensitization in the marine mollusk Aplysia can be successfully transferred by injecting RNA from sensitized into naïve animals. Moreover, a specific cellular alteration that underlies sensitization in Aplysia, sensory neuron hyperexcitability, can be reproduced by exposing sensory neurons in vitro to RNA from trained animals. The results provide support for a nonsynaptic, epigenetic model of memory storage in Aplysia.