Newly identified sleep-wake and circadian circuits as potential therapeutic targets.

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

Sleep Biology: Tuning In While Tuned Out

SummaryThe barrel cortex and whisker thalamus preferentially respond to whisker movements during REM sleep in infant rats. Understanding why the brain tunes into sensory signals while it’s tuned out in sleep may provide clues about the functions of REM sleep

Newly Identified Sleep-Wake and Circadian Circuits as Potential Therapeutic Targets

Optogenetics and chemogenetics are powerful tools, allowing the specific activation or inhibition of targeted neuronal sub-populations. 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 (REM) sleep behavior disorder (RBD) offers new possibilities for treating RBD and neurodegenerative synucleinopathies, while 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 for circadian regulation of aggression or the photic regulation of arousal and mood (PRAM) pathway carry enormous potential for helping to reduce the socio-economic 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

Dopamine neurons in the ventral tegmental area modulate REM sleep.

identified periods of 'active sleep' that are marked by rapid-eye-movements that alternate with 'quiescent sleep' periods in human infants. Several years later Dement and Kleitman showed that rapid-eye-movements are correlated with specific patterns of brainwave activity and that vivid dreaming occurs during periods of rapid-eye-movements in human adults. Shortly thereafter, Jouvet identified a similar behavioural state in cats, showing that cats also experience periods of rapid-eye-movements that occur during periods of muscle atonia and wake-like cortical activity. REM sleep, or REM sleep-like states, have subsequently been identified in a variety of animals, including marsupials, birds, fish, insects, octopi, and lizards. These observations suggest that REM sleep is conserved across the animal kingdom and imply that REM sleep plays a role in normal biology and physiology. Although REM sleep was initially characterized by rapid-eye-movements, we now know that it is also characterized by a range of physiological features, including reduced amplitude and faster frequency cortical electroencephalogram (EEG) that is reminiscent of waking, high-amplitude theta waves in the hippocampus, active suppression of skeletal muscle activity (i.e., REM atonia), intermittent muscle twitches, autonomic and respiratory activation, fluctuations i