Out of Sync: Sleep–Wake Disruption and Abnormal Brain Rhythms in a Dopamine D2 Receptor Mouse Model of Schizophrenia

Schizophrenia is a severe psychiatric disorder characterized by disrupted sleep–wake regulation and abnormal brain oscillations. Clinical findings remain inconsistent because of disease heterogeneity and treatment effects. Genetically engineered mouse models provide a controlled approach to investigate the mechanisms underlying these alterations and identify potential biomarkers. We studied mutant mice lacking dopamine D2 receptors in parvalbumin interneurons using continuous 24-h wireless recordings of electrocorticogram, electromyogram, locomotor activity, and video monitoring in a low-intervention home-cage environment. A low-stress sleep deprivation protocol assessed responses to acute sleep loss. Mutant mice (n=17, mixed sex) reproduced key schizophrenia-related features. Both sexes showed shorter non-rapid eye movement (NREM) sleep episodes and increased wakefulness throughout the circadian cycle. After sleep deprivation, mutants displayed impaired nest-building behavior, reduced sleep spindle activity, and abnormal gamma oscillations and coherence, electrophysiological signatures linked to psychosis. These findings demonstrate that selective D2 receptor deletion in parvalbumin interneurons disrupts sleep, behavior, and cortical network activity, supporting this model for studying schizophrenia-related sleep dysfunction.