Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation

Mahesh M. Karnani; Cornelia Schöne; Edward F. Bracey; J. Antonio González; Paulius Viskaitis; Han Tao Li; Antoine Adamantidis; Denis Burdakov

doi:10.1016/j.pneurobio.2020.101771

Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation

Mahesh M. Karnani^*, Cornelia Schöne, Edward F. Bracey, J. Antonio González, Paulius Viskaitis, Han Tao Li, Antoine Adamantidis, Denis Burdakov

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	101771
Journal	Progress in Neurobiology
Volume	187
DOIs	https://doi.org/10.1016/j.pneurobio.2020.101771
Publication status	Published - Apr 2020
Externally published	Yes

Funding

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 .

Funders	Funder number
Alan Ling and Adam Hurst
Markus Marks
University of Bern
Wellcome Trust
Francis Crick Institute
Horizon 2020 Framework Programme
H2020 Marie Skłodowska-Curie Actions	701986
Inselspital, Universitätsspital Bern
Medical Research Council
Cancer Research UK	FC001055
European Research Council
Human Frontier Science Program
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Horizon 2020

Keywords

Ensemble imaging
Hypothalamus
Locomotion
orexin/hypocretin neurons
Sensorimotor processing

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title = "Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation",

abstract = "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.",

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AU - Bracey, Edward F.

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AU - Li, Han Tao

AU - Adamantidis, Antoine

AU - Burdakov, Denis

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AB - 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.

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Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation

Abstract

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Keywords

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