While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid autonomic cardiovascular regulation during physical activity remains elusive. This study aimed to elucidate the role of the orexinergic nervous system in transmitting volitional motor signals, i.e. central command, to drive somatomotor and sympathetic cardiovascular responses. We first found that this system is activated by voluntary locomotor exercise as evidenced by an increased expression of Fos, a marker of neural activation, in the orexinergic neurons of Sprague–Dawley rats engaged in spontaneous wheel running. Next, using transgenic Orexin-Cre rats for optogenetic manipulation of orexinergic neurons, we found that optogenetic excitation of orexinergic neurons caused sympathoexcitation on a subsecond timescale under anaesthesia. In freely moving conscious rats, this excitatory stimulation rapidly elicited exploration-like behaviours, predominantly locomotor activity, along with pressor and tachycardiac responses. Meanwhile, optogenetic inhibition of orexinergic neurons during spontaneous wheel running immediately suppressed locomotor activities and blood pressure elevation without affecting basal cardiovascular homeostasis. Taken together, these findings demonstrate the essential role of the orexinergic nervous system in the central circuitry that transmits central command signals for locomotor exercise. This study not only offers insights into the brain circuit mechanisms precisely regulating autonomic cardiovascular systems during voluntary exercise but also likely contributes to our understanding of brain mechanisms underlying abnormal cardiovascular adjustments to exercise in pathological conditions, such as hypertension.

虽然下丘脑食欲能神经系统被认为在各种机体功能（包括觉醒、新陈代谢和高血压状态）的长期调节中发挥着关键作用，但该系统是否有助于身体活动期间快速自主心血管调节仍然难以捉摸。本研究旨在阐明食欲能神经系统在传递意志运动信号（即中枢命令）以驱动躯体运动和交感心血管反应中的作用。我们首先发现该系统是由自愿运动运动激活的，这一点可以通过参与自发轮跑的 Sprague-Dawley 大鼠的食欲素能神经元中 Fos（神经激活标记物）的表达增加来证明。接下来，使用转基因 Orexin-Cre 大鼠对食欲素能神经元进行光遗传学操作，我们发现食欲素能神经元的光遗传学激发在麻醉下在亚秒级时间内引起交感神经兴奋。在自由活动的有意识的大鼠中，这种兴奋性刺激迅速引发类似探索的行为，主要是自发活动，以及升压和心动过速反应。同时，自发轮跑期间食欲素能神经元的光遗传学抑制立即抑制了运动活动和血压升高，而不影响基础心血管稳态。总而言之，这些发现证明了食欲素能​​神经系统在传输运动锻炼的中央命令信号的中央电路中的重要作用。这项研究不仅提供了对自愿运动期间精确调节自主心血管系统的大脑回路机制的见解，而且可能有助于我们理解在病理条件下（例如高血压）运动时异常心血管调节的大脑机制。