A neural circuit state change underlying skilled movements

Mark J Wagner; Joan Savall; Oscar Hernandez; Gabriel Mel; Hakan Inan; Oleg Rumyantsev; Jérôme Lecoq; Tony Hyun Kim; Jin Zhong Li; Charu Ramakrishnan; Karl Deisseroth; Liqun Luo; Surya Ganguli; Mark J Schnitzer

doi:10.1016/j.cell.2021.06.001

A neural circuit state change underlying skilled movements

Cell. 2021 Jul 8;184(14):3731-3747.e21. doi: 10.1016/j.cell.2021.06.001. Epub 2021 Jul 1.

Authors

Mark J Wagner¹, Joan Savall², Oscar Hernandez³, Gabriel Mel⁴, Hakan Inan⁵, Oleg Rumyantsev⁶, Jérôme Lecoq⁷, Tony Hyun Kim⁸, Jin Zhong Li⁷, Charu Ramakrishnan⁹, Karl Deisseroth⁹, Liqun Luo¹⁰, Surya Ganguli¹¹, Mark J Schnitzer¹²

Affiliations

¹ Neurosciences Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: mjwagner@stanford.edu.
² Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
³ CNC Program, Stanford University, Stanford, CA 94305, USA.
⁴ Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
⁵ CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
⁶ CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
⁷ CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
⁸ Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
⁹ Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
¹⁰ Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
¹¹ Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
¹² Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA. Electronic address: mschnitz@stanford.edu.

Abstract

In motor neuroscience, state changes are hypothesized to time-lock neural assemblies coordinating complex movements, but evidence for this remains slender. We tested whether a discrete change from more autonomous to coherent spiking underlies skilled movement by imaging cerebellar Purkinje neuron complex spikes in mice making targeted forelimb-reaches. As mice learned the task, millimeter-scale spatiotemporally coherent spiking emerged ipsilateral to the reaching forelimb, and consistent neural synchronization became predictive of kinematic stereotypy. Before reach onset, spiking switched from more disordered to internally time-locked concerted spiking and silence. Optogenetic manipulations of cerebellar feedback to the inferior olive bi-directionally modulated neural synchronization and reaching direction. A simple model explained the reorganization of spiking during reaching as reflecting a discrete bifurcation in olivary network dynamics. These findings argue that to prepare learned movements, olivo-cerebellar circuits enter a self-regulated, synchronized state promoting motor coordination. State changes facilitating behavioral transitions may generalize across neural systems.

Keywords: Purkinje cells; calcium imaging; cerebellum; climbing fibers; coupled oscillators; motor learning; neural circuit dynamics; state change; synchronization; two-photon microscopy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Action Potentials / physiology
Animals
Calcium / metabolism
Cerebellum / physiology
Cortical Synchronization
Forelimb / physiology
Interneurons / physiology
Learning
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Neurological
Motor Activity / physiology
Movement / physiology*
Nerve Net / physiology*
Olivary Nucleus / physiology
Optogenetics
Purkinje Cells / physiology
Stereotyped Behavior
Task Performance and Analysis

Substances

Calcium

Grants and funding

HHMI/Howard Hughes Medical Institute/United States