The astrocyte clock controls circadian perineuronal net remodeling, synapse strength and learning behavior

Abstract

The circadian clock controls a vast array of cellular and organismal functions, from the molecular scale to behavior. While each cell is regimented by a cell-autonomous clock, few studies in the brain have dissected the circuit and behavioral contributions of cell-specific clocks. Relatedly, astrocytes are now known to play key roles in regulating synaptic function, circuit activity and behavior, but whether these functions are guided by astrocyte-autonomous clocks is unknown. Here, we report that post-natal deletion of the critical circadian clock gene Bmal1 in astrocytes, which abrogates core clock function in a cell type specific manner, induced expression of genes related to extracellular matrix (ECM) production, maintenance, and remodeling. Circadian variations have been shown in a specific ECM structure, perineuronal nets (PNNs), which are implicated in synaptic function and plasticity. In astrocyte-specific Bmal1 knockouts, hippocampal PNN abundance was decreased, and the circadian rhythm of these structures was also abolished. In line with evidence implicating PNNs, and the ECM in general, in synaptic function and plasticity, we found that astrocyte-specific Bmal1 KO mice had increased synaptic strength but blunted long term potentiation (LTP), as well as impaired learning and memory performance in a novel object recognition task. Taken together, these findings suggest that the astrocyte circadian clock regulates circadian rhythms in perineuronal net abundance as well as synaptic plasticity and behavioral learning and memory.