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

Apr 10, 2026bioRxiv : the preprint server for biology

The brain support cell clock controls daily changes in nerve cell coverings, connection strength, and learning

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Abstract

Post-natal deletion of a key circadian clock gene in astrocytes led to decreased perineuronal net abundance and disrupted circadian rhythms.

Astrocyte-specific deletion of the circadian clock gene resulted in increased expression of genes related to extracellular matrix production and remodeling.
The absence of the astrocyte circadian clock was associated with a decrease in the abundance of perineuronal nets in the hippocampus.
Circadian rhythms of perineuronal nets were abolished in astrocyte-specific knockout mice.
Astrocyte-specific knockout mice exhibited increased synaptic strength but impaired long-term potentiation.
Learning and memory performance was negatively affected in astrocyte-specific knockout mice during a novel object recognition task.

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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 genein 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-specificknockouts, 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-specificKO 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. Bmal1Bmal1Bmal1