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Behav Brain Res. 2016 Jul 15;308:222-35. doi: 10.1016/j.bbr.2016.04.027. Epub 2016 May 4.

Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits.

Author information

1
Department of Neuroscience, Ohio State University, Columbus, OH, USA.
2
Division of Pharmacology, Ohio State University, Columbus, OH, USA.
3
Department of Neuroscience, Ohio State University, Columbus, OH, USA. Electronic address: obrietan.1@osu.edu.

Abstract

A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day.

KEYWORDS:

BMAL1; Brain and muscle Arnt-like protein-1; Circadian; Learning; Memory

PMID:
27091299
PMCID:
PMC5344043
DOI:
10.1016/j.bbr.2016.04.027
[Indexed for MEDLINE]
Free PMC Article

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