Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies

Yukinori Hirano (), Kunio Ihara, Tomoko Masuda, Takuya Yamamoto, Ikuko Iwata, Aya Takahashi, Hiroko Awata, Naosuke Nakamura, Mai Takakura, Yusuke Suzuki, Junjiro Horiuchi, Hiroyuki Okuno and Minoru Saitoe ()
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Yukinori Hirano: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Kunio Ihara: Center of Gene Research, Nagoya University
Tomoko Masuda: Tokyo Metropolitan Institute of Medical Science
Takuya Yamamoto: Center for iPS Cell Research and Application, Kyoto University
Ikuko Iwata: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Aya Takahashi: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Hiroko Awata: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Naosuke Nakamura: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Mai Takakura: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Yusuke Suzuki: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Junjiro Horiuchi: Tokyo Metropolitan Institute of Medical Science
Hiroyuki Okuno: SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine
Minoru Saitoe: Tokyo Metropolitan Institute of Medical Science

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13471

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