Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13554-y
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Funding
- MEXT-Supported Program for the Strategic Research Foundation at Private Universities [S1311017]
- Core Research for Evolutional Science and Technology (CREST), Japan
- Sumitomo Foundation, Japan
- Takeda Science Foundation, Japan
- Naito Foundation
- Uehara Memorial Foundation
- Science Research Promotion Fund
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- [15H02488]
- [18H03944]
- [19H01047]
- [23300120]
- [20380078]
- [24650172]
- [26640014]
- [17K19464]
- [17H05962]
- [18022038]
- [22022039]
- [24116008]
- [24116001]
- [23115716]
- [17H06084]
- [17H05961]
- [17H05581]
- [18H05428]
- [18H05434]
- [19H04917]
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Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the late afternoon-early evening. However, functional roles of local brain circadian clocks in memory performance remains unclear. Here, we show that hippocampal clock controlled by the circadian-dependent transcription factor BMAL1 regulates time-of-day retrieval profile. Inducible transgenic dominant negative BMAL1 (dnBMAL1) expression in mouse forebrain or hippocampus disrupted retrieval of hippocampal memories at Zeitgeber Time 8-12, independently of retention delay, encoding time and Zeitgeber entrainment cue. This altered retrieval profile was associated with downregulation of hippocampal Dopamine-cAMP signaling in dnBMAL1 mice. These changes included decreases in Dopamine Receptors (D1-R and D5-R) and GluA1-S845 phosphorylation by PKA. Consistently, pharmacological activation of cAMP-signals or D1/5Rs rescued impaired retrieval in dnBMAL1 mice. Importantly, GluA1 S845A knock-in mice showed similar retrieval deficits with dnBMAL1 mice. Our findings suggest mechanisms underlying regulation of retrieval by hippocampal clock through D1/5R-cAMP-PKA-mediated GluA1 phosphorylation.
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