Subsecond Ensemble Dynamics of Orexin Neurons Link Sensation and Action

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.