Newly identified sleep–wake and circadian circuits as potential therapeutic targets

Sleep

Fraigne, Jimmy^3¹  Anaclet, Christelle^7²  Venner, Anne^1,2³  Todd, William D^1,2⁴  Bowrey, Hannah^4,5⁵  Kaur, Satvinder^1,2⁶  Eban-Rothschild, Ada^6⁷ 

[1] Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada^3;Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, NeuroNexus Institute, Graduate Program in Neuroscience – Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA^7;Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA^1;Department of Neurology, Harvard Medical School, Boston, MA^2;Department of Psychiatry, Rutgers Biomedical Health Sciences, Rutgers University, Newark, NJ^4;Department of Psychology, University of Michigan, Ann Arbor, MI^6;Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia^5

关键词: parafacial zone;    ventral tegmental area;    hypercapnia;    REM behavioral disorder;    aggression;    photic regulation of arousal and mood;   

DOI  :  10.1093/sleep/zsz023

学科分类：生理学

来源: American Academy of Sleep Medicine

【 摘 要 】

Optogenetics and chemogenetics are powerful tools, allowing the specific activation or inhibition of targeted neuronal subpopulations. Application of these techniques to sleep and circadian research has resulted in the unveiling of several neuronal populations that are involved in sleep–wake control, and allowed a comprehensive interrogation of the circuitry through which these nodes are coordinated to orchestrate the sleep–wake cycle. In this review, we discuss six recently described sleep–wake and circadian circuits that show promise as therapeutic targets for sleep medicine. The parafacial zone (PZ) and the ventral tegmental area (VTA) are potential druggable targets for the treatment of insomnia. The brainstem circuit underlying rapid eye movement sleep behavior disorder (RBD) offers new possibilities for treating RBD and neurodegenerative synucleinopathies, whereas the parabrachial nucleus, as a nexus linking arousal state control and breathing, is a promising target for developing treatments for sleep apnea. Therapies that act upon the hypothalamic circuitry underlying the circadian regulation of aggression or the photic regulation of arousal and mood pathway carry enormous potential for helping to reduce the socioeconomic burden of neuropsychiatric and neurodegenerative disorders on society. Intriguingly, the development of chemogenetics as a therapeutic strategy is now well underway and such an approach has the capacity to lead to more focused and less invasive therapies for treating sleep–wake disorders and related comorbidities.

【 授权许可】

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