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Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation.

Abstract：

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Hasegawa S,Fukushima H,Hosoda H,Serita T,Ishikawa R,Rokukawa T,Kawahara-Miki R,Zhang Y,Ohta M,Okada S,Tanimizu T,Josselyn SA,Frankland PW,Kida S

doi

10.1038/s41467-019-13554-y

subject

Has Abstract

pub_date

2019-12-18 00:00:00

pages

5766

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13554-y

journal_volume

10

pub_type

杂志文章

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