Orexin (hypocretin) participates in central autonomic regulation during fight-or-flight response.

Our daily life does not only involve a calm resting state but is rather full of perturbations that induce active states such as moving, eating, and communicating. During such active conditions, cardiorespiratory regulation should be adjusted according to bodily demand, which differs from that during the resting state, by modulating or resetting the operating point. To explore neural mechanisms in the state-dependent adjustment of central autonomic regulation, my research group has recently focused on the fight-or-flight response because the stressor induces not only cognitive, emotional, and behavioral changes but also autonomic changes. In this brief review, I will summarize our discovery using orexin knockout mice and orexin neuron-ablated mice for the possible contribution of orexin, a hypothalamic neuropeptide, to the state-dependent adjustment of the central autonomic regulation. In addition, I will introduce some recent discovery using optogenetic manipulation of the orexin and related systems. The diversity of synaptic control of the cardiovascular and respiratory neurons appears necessary for animals to adapt themselves to ever-changing life circumstances and behavioral states. The orexin system is likely to function as one of the essential modulators for coordinating the circuits controlling autonomic functions and behaviors.