DNMT1 function in cortical PV interneurons modulates cortical network activity, mood disorder‑related behavior, and perineuronal nets.

Loss of DNMT1 in cortical PV interneurons increases PV spiking but reduces inhibitory efficacy, leading to network desynchronization and depression- and anxiety-like behaviors in mice.

• Why it matters: Understanding how epigenetic regulation in PV interneurons influences cortical network stability and mood-related behaviors can reveal mechanisms underlying psychiatric disorders.
• What they did: The study used conditional PV-specific Dnmt1 deletion combined with single-nucleus RNA-seq, snATAC-seq, electrophysiology, histology, and behavioral tests to investigate effects on neural circuits and tissue organization.
• The result: Findings show DNMT1 loss causes transcriptional and chromatin changes affecting PNN organization and neuron-glia communication, impairing PNN formation and disrupting cortical network synchronization.