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

Olga Barca-Mayo (), Meritxell Pons-Espinal, Philipp Follert, Andrea Armirotti, Luca Berdondini and Davide De Pietri Tonelli ()
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Olga Barca-Mayo: Neurobiology of miRNA Lab, Fondazione Istituto Italiano di Tecnologia
Meritxell Pons-Espinal: Neurobiology of miRNA Lab, Fondazione Istituto Italiano di Tecnologia
Philipp Follert: Neurobiology of miRNA Lab, Fondazione Istituto Italiano di Tecnologia
Andrea Armirotti: D3 PharmaChemistry, Fondazione Istituto Italiano di Tecnologia
Luca Berdondini: NetS3 Lab, Fondazione Istituto Italiano di Tecnologia
Davide De Pietri Tonelli: Neurobiology of miRNA Lab, Fondazione Istituto Italiano di Tecnologia

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14336

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