Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Front Neurol Neurosci. 2021;45:52-60. doi: 10.1159/000514957. Epub 2021 May 28.
Hypothalamic hypocretin/orexin neurons have been initially conceptualized as slow, modulatory controllers of behavior. Furthermore, their behavioral effects have been assumed to be a secondary consequence of their impact on arousal. However, cellular-resolution calcium imaging and optogenetic studies show that orexin neurons regulate self-generated and sensory-evoked movement on rapid, subsecond timescales. Orexin cell activity rapidly and transiently peaks before and during movements. Optogenetic prevention of this activation reduces the probability of locomotion initiation, and optogenetic mimicry of orexin cell activation rapidly causes locomotion. Neural ensemble calcium imaging experiments reveal that the same orexin cells whose activity underlies movement initiation display subsecond-latency responses to diverse sensory stimuli. These findings establish orexin neurons as rapid and strong sensorimotor controllers that are in many ways operationally similar to classic subcortical movement controllers, such as midbrain dopamine neurons. While a scientific definition of "arousal" is still lacking, the subsecond-scale sensorimotor control by orexin neurons could be viewed as reminiscent of a motor rather than an arousal system.
下丘脑食欲素/下丘脑分泌素神经元最初被概念化为行为的缓慢调节控制器。此外，人们认为它们对觉醒的影响是其行为效应的次要后果。然而，细胞分辨率钙成像和光遗传学研究表明，食欲素神经元在快速的亚秒时间尺度上调节自我产生的和感觉诱发的运动。食欲素细胞的活动在运动前和运动期间迅速而短暂地达到峰值。光遗传学预防这种激活会降低运动起始的概率，而光遗传学模拟食欲素细胞的激活会迅速引起运动。神经集合钙成像实验表明，启动运动所依赖的相同食欲素细胞对各种感觉刺激表现出亚秒级潜伏期反应。这些发现确立了食欲素神经元作为快速而强大的感觉运动控制器，在许多方面与经典的皮质下运动控制器（如中脑多巴胺神经元）操作相似。虽然“觉醒”的科学定义仍然缺乏，但食欲素神经元的亚秒级感觉运动控制可以被视为类似于运动系统而不是觉醒系统。
