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Discovery reveals circuitry of fundamental motor circuit

Martyn Goulding

The spinal cord contains a network of neurons that are able to operate largely in an autonomous manner, thus allowing animals to carry out simple rhythmic walking movements with minimal attention–giving us the ability, for example, to walk while talking on the phone. These circuits control properties such as stepping with each foot or pacing the tempo of walking or running.

Recently, a team of researchers led by Martyn Goulding identified for the first time which neurons in the spinal cord are responsible for controlling a key output of this locomotion circuit, namely, the ability to synchronously activate and deactivate opposing muscles to create a smooth bending motion (dubbed flexor-extensor alternation). The findings were published in Neuron.

Motor circuits in the spinal cord are assembled from six major types of interneurons–cells that interface between nerves descending from the brain and nerves that activate or inhibit muscles.

V2b interneurons, responsible for a key locomotion circuit, appear as green with yellow nuclei in a spinal cord while all other neurons are red.

Goulding and his group had previously implicated one class of interneurons, V1, as being a likely key component of the flexor-extensor circuitry. When V1 interneurons were removed, however, the team saw that flexor-extensor activity was still intact, leading them to suspect that another type of cell was also involved.

To determine what other interneurons were at play in the flexor-extensor circuit, the team looked for other cells in the spinal cord with properties similar to those of the V1 interneurons and began to focus on another class of neuron whose function was not known–V2b interneurons. Using a specialized experimental setup that allows one to monitor locomotion in the spinal cord itself, the team saw a synchronous pattern of flexor and extensor activity when V2b interneurons were inactivated along with the V1 interneurons.

“Our whole motor system is built around flexor-extension; this is the cornerstone component of movement,” says Goulding, who holds Salk’s Frederick W. and Joanna J. Mitchell Chair. “If you really want to understand how animals move, you need to understand the contribution of these switching cells.”

Goulding’s discovery may pave the way for new therapies for spinal cord injuries or other motor impairments related to disease.