Sleep circuit modulation: from animal models to human translation

Abstract Sleep occupies one-third of human life and serves critical functions in memory consolidation, metabolic regulation and neural homeostasis. Sleep disorders affect over 70 million people globally and are prevalent across neurodegenerative, psychiatric and neurological conditions. Recent advances in optogenetics and chemogenetics have enabled precise control of sleep-wake transitions in animal models, demonstrating that sleep can be actively modulated through targeted circuit manipulation. However, translating these findings to human applications faces substantial challenges. This review synthesizes current understanding of sleep circuit organization from animal studies, examines effects of direct brain stimulation on human sleep across diverse targets, analyzes discrepancies between animal and human findings and proposes translational strategies. While some principles appear conserved across species, significant differences in circuit architecture, technical capabilities and regulatory constraints necessitate novel approaches for human sleep modulation. We outline emerging solutions including improved spatiotemporal precision, oscillatory targeting and disease-specific interventions that may bridge the translational gap.