Daily cycles in brain immune cells influence early brain connection growth differently in males and females

Hippocampal microglia in adolescent mice show diurnal transcriptional rhythms, with gene expression related to synaptic pruning peaking during the rest phase.

• Inducible deletion of the core clock gene Bmal1 in microglia disrupts these diurnal rhythms.
• In male mice, clock disruption results in increased synapse engulfment, reduced dendritic spine density, and decreased synaptic connectivity.
• Female mice exhibit similar reductions in synaptic connectivity but do not show significant changes in postsynaptic structure.
• Microglial clock disruption leads to broad, sex-specific alterations in gene expression related to synapses, aligning with pathways associated with neurodevelopmental disorders.
• This disruption is linked to impaired memory and sociability, suggesting a critical role for microglial clocks in refining synapses during development.

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