Summary Appropriate motor control is critical for normal life, and requires hypothalamic hypocretin/orexin neurons (HONs). HONs are slowly regulated by nutrients, but also display rapid (subsecond) activity fluctuations in vivo. The necessity of these activity bursts for sensorimotor control and their roles in specific phases of movement are unknown. Here we show that temporally-restricted optosilencing of spontaneous or sensory-evoked HON bursts disrupts locomotion initiation, but does not affect ongoing locomotion. Conversely, HON optostimulation initiates locomotion with subsecond delays in a frequency-dependent manner. Using 2-photon volumetric imaging of activity of >300 HONs during sensory stimulation and self-initiated locomotion, we identify several locomotion-related HON subtypes, which distinctly predict the probability of imminent locomotion initiation, display distinct sensory responses, and are differentially modulated by food deprivation. By causally linking HON bursts to locomotion initiation, these findings reveal the sensorimotor importance of rapid spontaneous and evoked fluctuations in HON ensemble activity.
Bibliographical noteFunding Information:
We thank Markus Marks and other Fatih Yanik lab members for help with machine learning, Lise T. Jensen and Lars Fugger for sharing O-DTR mice, Takeshi Sakurai for sharing the orexin promoter used for generating HON specific constructs, Alan Ling and Adam Hurst at the Francis Crick Institute mechanical workshop for making recording arenas, staff at Vigene for technical assistance with viruses, Bruno Pichler and Dale Elgar for microscope design, Troy Margrie for sharing equipment, and all Burdakov lab members for useful comments and help. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement DRIVOME (grant agreement 701986 ). This work was funded by The Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001055 ), the UK Medical Research Council ( FC001055 ), and the Wellcome Trust ( FC001055 ). AA was supported by the Human Frontier Science Program , Inselspital University Hospital Bern , Swiss National Science Foundation , European Research Council , the University of Bern and the Bern University Hospital .
- orexin/hypocretin neurons
- sensorimotor processing
- ensemble imaging
- Ensemble imaging