IInstinctive behaviors, such as sleep/wakefulness, feeding and sexual behaviors are regulated by the hypothalamic neurons. Recent research revealed that the hypothalamic neurons containing neuropeptides are implicated in the regulation of these instinctive behaviors. It is essential to study neural regulatory mechanisms of these instinctive behaviors using a whole animal since these instinctive behaviors are exhibited only therein. Optogenetics enable control of the activity of specific type of neurons in the whole body animal using light. We apply optogenetics to Orexin/hypocretin-producing neurons (orexin neurons). Orexin neurons are located in the hypothalamus but project their efferents throughout the brain. Intriguingly, mice lacking the prepro-orexin gene showed behavioral characteristics similar to human sleep disorder “Narcolepsy”, that is a fragmentation of sleep/wakefulness and sudden muscle weakness. Human clinical studies also showed that orexin neurons are specifically degenerated in the narcoleptic patient’s brain. These results suggest that the orexin neurons play a critical role in the regulation of sleep/wakefulness. Previous studies using electrophysiological in vitro techniques have identified potential neuronal pathways or networks connecting orexin neurons with other neurons which are known to be involved in sleep/ wakefulness regulation. To apply optogenetics to orexin neurons, we generated transgenic mice in which specifically express halorhodopsin or Archaerhodopsin-3, a light driven neural silencer. In these mice brain more than 90% of orexin neurons express halorhodopsin or Archaerhodopsin-3. Acute inhibition of orexin neurons (~1hr) using optogenetics induced fragmentation of sleep/wakefulness in the early dark period (Figure), but not cataplexy-like behavioral arrest, which is characteristic symptom in narcoleptic patient. This result might suggest that chronic inhibition of orexin neurons might be caused to trigger cataplexy-like behavioral arrest. Our current research involves applying optogenetics in the hypothalamic peptide-containing neurons to reveal regulatory mechanisms of these instinctive behaviors.