Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling

Nat Commun. 2017 Feb 10;8:14336. doi: 10.1038/ncomms14336.

Abstract

Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown. Here we show that ablation of Bmal1 in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic Bmal1 has an impact on the neuronal clock through GABA signalling. Importantly, pharmacological modulation of GABAA-receptor signalling completely rescues the behavioural phenotypes. Our results reveal a crucial role of astrocytic Bmal1 for the coordination of neuronal clocks and propose a new cellular target, astrocytes, for neuropharmacology of transient or chronic perturbation of circadian rhythms, where alteration of astrocytic clock genes might contribute to the impairment of the neurobehavioural outputs such as cognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism*
  • Animals
  • Astrocytes / metabolism*
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology
  • Cognition / physiology*
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Neurons / metabolism
  • Sequence Deletion
  • Signal Transduction
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • gamma-Aminobutyric Acid