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

Area of Science:

• Neuroscience
• Chronobiology
• Cell Biology

Background:

• The circadian clock regulates diverse cellular and organismal functions.
• Astrocytes play critical roles in synaptic function, neural circuit activity, and behavior.
• The role of astrocyte-autonomous clocks in these functions remains largely unknown.

Purpose of the Study:

• To investigate the contribution of astrocyte-autonomous circadian clocks to brain function and behavior.
• To determine if astrocyte-specific deletion of the Bmal1 gene impacts extracellular matrix and synaptic plasticity.

Main Methods:

• Post-natal deletion of the Bmal1 gene specifically in astrocytes.
• Analysis of gene expression related to extracellular matrix (ECM) production and remodeling.
• Assessment of perineuronal net (PNN) abundance and circadian rhythms in the hippocampus.
• Electrophysiological recordings to measure synaptic strength and long-term potentiation (LTP).
• Behavioral testing using a novel object recognition task to evaluate learning and memory.

Main Results:

• Astrocyte-specific Bmal1 knockout induced genes involved in ECM production and remodeling.
• Hippocampal PNN abundance decreased, and their circadian rhythm was abolished in knockout mice.
• Knockout mice exhibited increased synaptic strength but blunted LTP.
• Impaired learning and memory performance was observed in the novel object recognition task.

Conclusions:

• The astrocyte circadian clock regulates circadian rhythms of PNN abundance.
• Astrocyte clocks are crucial for maintaining synaptic plasticity.
• Astrocyte circadian clocks significantly influence behavioral learning and memory processes.