Abstract
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. It is well established that orexin neurons, which are located in this region, play a critical role in this response. In this study, we further examined this role by recording orexin neuronal activity and heart rate in freely moving mice using an original dual-channel fiber photometry system in vivo. Analysis of orexin neuron activity in relation to autonomic responses to aversive stimuli 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 memory of the aversive stimulus activated orexin neurons and increased heart rate. Our data suggest that orexin neurons are a key component linking aversive emotions to autonomic defense response. Our data also suggest that targeting orexin neurons may enable treatment of psychiatric disorders associated with chronic stress and traumatic memories.
Highlights
Stress is often mistakenly thought of as being purely detrimental
The AAV mixture consisting of AAVDJ-tetO-G-CaMP6 and AAVDJ-tetO-mCherry was stereotaxically injected into the hypothalamus of ORX-tTA mice that express tetracycline transactivator in orexin neurons (Fig. 1A)
A possible causal relationship between orexin neuronal activity and heart rate increase When focusing on the differences between the starting point of the orexin neuronal activity increase and the starting point of the heart rate increase, we found that the onset of the increase in orexin neuronal activity always preceded changes in heart rate (Fig. 3B)
Summary
Stress is often mistakenly thought of as being purely detrimental. While it is true that excessive stress generally has negative effects that can cause various mental disorders and emotional disturbances [1], responses to acute stress can be beneficial and even indispensable for life because they protect against potential sources of danger. Acute stress induces a rise in blood pressure, heart rate, respiration, and stress-induced analgesia. These autonomic changes are collectively called the defense response and prepare for and support fight-or-flight behavior [2]. Orexin neurons are essential to autonomic defense responses induced by stress in general, little is known about their neuronal activity in response to specific stressors. The hypothalamus contains many different cell types and targeting only the orexin-producing neurons of interest proved difficult. Some researchers have reported on the activity of orexin neurons in awake rats by using traditional electrophysiological methods such as extracellular recording
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