title: Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies.
abstract: Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requires the CREB transcription factor and its coactivator, CBP, subsequent early maintenance requires CREB and a different coactivator, CRTC. Late maintenance becomes CREB independent and instead requires the transcription factor Bx. Bx expression initially depends on CREB/CRTC activity, but later becomes CREB/CRTC independent. The timing of the CREB/CRTC early maintenance phase correlates with the time window for LTM extinction and we identify different subsets of CREB/CRTC target genes that are required for memory maintenance and extinction. Furthermore, we find that prolonging CREB/CRTC-dependent transcription extends the time window for LTM extinction. Our results demonstrate the dynamic nature of stored memory and its regulation by shifting transcription systems in the MBs.
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.|Japan Science and Technology Agency, PRESTO, 4-4-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Center of Gene Research, Nagoya University, Huro-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Ihara
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-0057, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Center for iPS Cell Research and Application, Department of Reprogramming Science, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.|AMED-CREST, AMED 1-7-1 Otemach, Chiyodaku, Tokyo 100-0004, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Iwata
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Awata
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.|Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto City 603-8555, Japan.
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Takakura
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-0057, Japan.
authors.forename: Junjiro
authors.initials: J
authors.lastname: Horiuchi
authors.affiliation: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuno
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-0057, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Saitoe
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D063990:Gene Ontology; D057567:Memory, Long-Term; D024521:Mushroom Bodies / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C578084:CRTC protein, Drosophila; D017362:Cyclic AMP Response Element-Binding Protein; D029721:Drosophila Proteins; D014157:Transcription Factors