Ventral spinocerebellar tract neurons are essential for mammalian locomotion

Joshua Chalif, MD, PhD
Department of Neurosurgery
Division of Basic Neuroscience Research
Poster Overview

Locomotion can take many forms in different species such as swimming, crawling, or running. In all species, locomotion is critical for finding food or shelter, finding a mate, and avoiding predators, all necessary for survival. We know that neurons within the spinal cord are responsible for the generation of locomotion. These neurons have been termed the central pattern generator and produce rhythmic activity to generate locomotion in all vertebrates, including humans. Yet, despite recent advances in the molecular identification of several spinal cord interneurons, we still lack a fine understanding of the neurons responsible for generating locomotion. Here, we provide multimodal evidence that a class of spinal cord interneurons, the ventral spinocerebellar tract (VSCT) neurons are critical for the production of locomotion in mice. We show that activating these neurons induces locomotion, whereas silencing these neurons prevents locomotion. VSCT neuron connectivity to other interneurons and their own intrinsic properties also support a role in locomotion. These findings are important because a better understanding of spinal circuitry will be invaluable in developing potential treatments for spinal cord injury. Indeed, activating VSCT neurons after spinal cord injury may prove to be a new therapeutic technique to help restore locomotion in patients.

Scientific Abstract

Locomotion is a complex behavior but essential for animal survival. Vertebrate locomotion depends upon a set of spinal cord interneurons, which are responsible for controlling the alternation of flexor and extensor muscles as well as muscles of the left and right side of the body. While the organization of the neuronal circuits underlying left-right and flexor-extensor alternation is beginning to emerge, it is unknown whether a unique set of spinal neurons is responsible for the generation and maintenance of locomotor behavior. Here, we show that ventral spinocerebellar tract (VSCT) neurons are capable of inducing and maintaining locomotor-like behavior in neonatal mice. VSCTs exhibit intrinsic functional properties and neuronal circuit connectivity that support a role in locomotor rhythmogenesis. Optogenetic activation of VSCT neurons can produce locomotor behavior, whereas chemogenetic silencing of VSCTs prevents the induction of locomotion. Together, these experiments reveal that VSCT neurons are both necessary and sufficient for the production of locomotor behavior. Thus, VSCT neurons are essential for mammalian locomotion and may represent a new therapeutic target for spinal cord injury.

Clinical Implications
Understanding the basic mechanisms responsible for locomotion is critical for developing targeted therapy to help patients suffering from gait abnormalities. These patients, such as spinal cord injury patients, may benefit from VSCT neuron activation in an effort to restore locomotion.
Research Areas
Authors
Joshua Chalif, George Mentis
Principal Investigator
George Mentis

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