Aversive Emotion Activates Orexin Neurons and Induces Tachycardia in Freely Moving Mice

Abstract Stress affects the sensory and negative emotional components in the brain and causes autonomic responses and aversive emotion. However, the possible roles for the negative emotional component remain largely unclear. The perifornical area of the hypothalamus has been known as the center for the defense response, or fight-or-flight response, which is characterized by a concomitant rise in arterial blood pressure, heart rate, and respiratory frequency. Orexin neurons located in that region are suggested to be a critical population responsible for that response. In this study, we examined the suggestion by recording orexin neuronal activity and heart rate in freely moving mice using an original dual-channel fiber photometry system in vivo. Association analysis between orexin neuronal activity and aversive stress-induced autonomic responses revealed a rapid increase in neuronal activity just prior to changes in heart rate. In addition, we examined whether orexin neurons would be activated by a conditioned neutral sound that was previously associated with aversive stimulus. We show that the negative emotional memory indeed activated orexin neurons and increased heart rate. Our data suggest that orexin neurons are the key component required to receive aversive emotion and link it with an autonomic defense response. Our data also suggest that targeting orexin neurons may enable treatment of psychiatric disorders that result from chronic stress and occur long after the original sensory inputs are gone.