RRC ID 57173
Author Miyashita T, Kikuchi E, Horiuchi J, Saitoe M.
Title Long-Term Memory Engram Cells Are Established by c-Fos/CREB Transcriptional Cycling.
Journal Cell Rep
Abstract Training-dependent increases in c-fos have been used to identify engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory engrams has been unclear. Formation of LTM of an aversive olfactory association in flies requires repeated training trials with rest intervals between trainings. Here, we find that prolonged rest interval-dependent increases in pERK induce transcriptional cycling between c-Fos and CREB in a subset of KCs in the mushroom bodies, where olfactory associations are made and stored. Preexisting CREB is required for initial c-fos induction, while c-Fos is required later to increase CREB expression. Blocking or activating c-fos-positive engram neurons inhibits memory recall or induces memory-associated behaviors. Our results suggest that c-Fos/CREB cycling defines LTM engram cells required for LTM.
Volume 25(10)
Pages 2716-2728.e3
Published 2018-12-4
DOI 10.1016/j.celrep.2018.11.022
PII S2211-1247(18)31768-6
PMID 30517860
MeSH Animals Cyclic AMP Response Element-Binding Protein / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / physiology* Enzyme Activation Extracellular Signal-Regulated MAP Kinases / metabolism Memory, Long-Term / physiology* Neurons / metabolism Phosphorylation Proto-Oncogene Proteins c-fos / metabolism* Transcription, Genetic*
IF 7.815
Times Cited 12