Elucidation of Neuronal Circuitry Involved in the Regulation of Sleep/Wakefulness Using Optogenetics

Although sleep is an absolutely essential physiological phenomenon to maintain normal health in animals, little is known about the function and regulatory mechanism of sleep so far. In this section, we introduce how optogenetics was applied to freely behaving animals to elucidate neuronal circuits involved in the regulation of sleep/wakefulness. When optogenetics was applied to the specific type of neurons involved in sleep/wakefulness regulation, we could control the sleep/wakefulness state, changes among wakefulness, non-rapid eye movement (NREM) sleep and REM sleep state. Selective activation of orexin neurons and noradrenergic neurons in the locus coeruleus (LC) using channelrhodopsin-2 and melanopsin induced the transition from sleep to wakefulness. In contrast, suppression of these using halorhodopsin and archaerhodopsin induced the transition from wakefulness to NREM sleep and increased the time spent in NREM sleep. Selective activation of melanin-concentrating hormone (MCH) neurons induced the transition from NREM sleep to REM sleep and prolonged the time spent in REM sleep accompanied by a decrease in time spent in NREM sleep. These studies help to answer how this specific type of neural activity contributes to the regulation of sleep/wakefulness.