Central control of interlimb coordination and speed-dependent gait expression in quadrupeds.

Authors:
Simon M Danner, PhD
Simon M Danner, PhD
Drexel College of Medicine
Research associate
Computational Neuroscience
Philadelphia, PA | United States
Natalia A Shevtsova
Natalia A Shevtsova
Drexel University College of Medicine
Dr. Ilya A Rybak, PhD
Dr. Ilya A Rybak, PhD
Drexel University College of Medicine
Professor
Neuroscience
Philadelphia, Pennsylvania | Afghanistan

J Physiol 2016 12 8;594(23):6947-6967. Epub 2016 Nov 8.

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.

Key Points: Quadrupeds express different gaits depending on speed of locomotion. Central pattern generators (one per limb) within the spinal cord generate locomotor oscillations and control limb movements. Neural interactions between these generators define interlimb coordination and gait. We present a computational model of spinal circuits representing four rhythm generators with left-right excitatory and inhibitory commissural and fore-hind inhibitory interactions within the cord. Increasing brainstem drive to all rhythm generators and excitatory commissural interneurons induces an increasing frequency of locomotor oscillations accompanied by speed-dependent gait changes from walk to trot and to gallop and bound. The model closely reproduces and suggests explanations for multiple experimental data, including speed-dependent gait transitions in intact mice and changes in gait expression in mutants lacking certain types of commissural interneurons. The model suggests the possible circuit organization in the spinal cord and proposes predictions that can be tested experimentally.

Abstract: As speed of locomotion is increasing, most quadrupeds, including mice, demonstrate sequential gait transitions from walk to trot and to gallop and bound. The neural mechanisms underlying these transitions are poorly understood. We propose that the speed-dependent expression of different gaits results from speed-dependent changes in the interactions between spinal circuits controlling different limbs and interlimb coordination. As a result, the expression of each gait depends on (1) left-right interactions within the spinal cord mediated by different commissural interneurons (CINs), (2) fore-hind interactions on each side of the spinal cord and (3) brainstem drives to rhythm-generating circuits and CIN pathways. We developed a computational model of spinal circuits consisting of four rhythm generators (RGs) with bilateral left-right interactions mediated by V0 CINs (V0 and V0 sub-types) providing left-right alternation, and conditional V3 CINs promoting left-right synchronization. Fore and hind RGs mutually inhibited each other. We demonstrate that linearly increasing excitatory drives to the RGs and V3 CINs can produce a progressive increase in the locomotor speed accompanied by sequential changes of gaits from walk to trot and to gallop and bound. The model closely reproduces and suggests explanations for the speed-dependent gait expression observed in vivo in intact mice and in mutants lacking V0 or all V0 CINs. Specifically, trot is not expressed after removal of V0 CINs, and only bound is expressed after removal of all V0 CINs. The model provides important insights into the organization of spinal circuits and neural control of locomotion.
PDF Download - Full Text Link
( Please be advised that this article is hosted on an external website not affiliated with PubFacts.com)
Source Status
http://dx.doi.org/10.1113/JP272787DOI ListingPossible
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134391PMCFound
December 2016
6 Reads
5.04 Impact Factor

Similar Publications

Organization of left-right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling.

J Physiol 2015 Jun;593(11):2403-26

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.

Key Points: Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left-right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D , V2a-V0V and V3 neuron populations. Read More

View Article
June 2015

Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds.

Elife 2017 Nov 22;6. Epub 2017 Nov 22.

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States.

Interactions between cervical and lumbar spinal circuits are mediated by long propriospinal neurons (LPNs). Ablation of descending LPNs in mice disturbs left-right coordination at high speeds without affecting fore-hind alternation. We developed a computational model of spinal circuits consisting of four rhythm generators coupled by commissural interneurons (CINs), providing left-right interactions, and LPNs, mediating homolateral and diagonal interactions. Read More

View Article
November 2017

Mechanisms of left-right coordination in mammalian locomotor pattern generation circuits: a mathematical modeling view.

PLoS Comput Biol 2015 May 13;11(5):e1004270. Epub 2015 May 13.

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

The locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed. Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Read More

View Article
May 2015

Phenotypic characterization of speed-associated gait changes in mice reveals modular organization of locomotor networks.

Curr Biol 2015 Jun 7;25(11):1426-36. Epub 2015 May 7.

Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden. Electronic address:

Studies of locomotion in mice suggest that circuits controlling the alternating between left and right limbs may have a modular organization with distinct locomotor circuits being recruited at different speeds. It is not clear, however, whether such a modular organization reflects specific behavioral outcomes expressed at different speeds of locomotion. Here, we use detailed kinematic analyses to search for signatures of a modular organization of locomotor circuits in intact and genetically modified mice moving at different speeds of locomotion. Read More

View Article
June 2015