Elucidation of neuronal circuitry involved in the regulation of sleep/wakefulness using optogenetics

Abstract

The mechanisms of instinctive behaviors such as feeding, drinking, sexual activity and sleep/wakefulness can only be studied in the whole animal with intact neural networks. This has been difficult due to lack of techniques to control the activity of specific neurons in intact animals. Optogenetics is a recent technique, which enables such control using light and allows the study of regulatory mechanisms of instinctive behaviors. In this section, we introduce how optogenetics was applied to orexin/hypocretin neurons to reveal the regulatory mechanisms of sleep and wakefulness. Activity manipulation of orexin neurons controls the state changes among wakefulness, non-rapid eye movement (NREM) sleep and REM sleep state. Selective activation of orexin neurons using channelrhodopsin-2 (ChR2) or melanopsin (OPN4) induced transition from sleep to wakefulness. In contrast, suppression of these neurons using halorhodopsin (HaloR) or archaerhodopsin (ArchR) induced transition from wakefulness to NREM sleep and increased the time spent in NREM sleep. These studies help answer how orexin neurons contribute to regulate sleep/wakefulness.