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Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.<br />The neural mechanisms that lead to a relative deficit in memory retrieval in the afternoon are unclear. Here, the authors show that the circadian - dependent transcription factor BMAL1 regulates retrieval through dopamine and glutamate receptor phosphorylation.
- Subjects :
- Male
0301 basic medicine
endocrine system
Science
Dopamine
Circadian clock
General Physics and Astronomy
Mice, Transgenic
Hippocampal formation
Biology
Hippocampus
Article
Long-term memory
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Circadian Clocks
Cyclic AMP
Zeitgeber
medicine
Animals
Gene Knock-In Techniques
Receptors, AMPA
Phosphorylation
lcsh:Science
Maze Learning
Multidisciplinary
ARNTL Transcription Factors
General Chemistry
Cyclic AMP-Dependent Protein Kinases
030104 developmental biology
Dopamine receptor
Mental Recall
Models, Animal
Forebrain
lcsh:Q
Female
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....e344db49a795375402baceec4e46c8e5