In a study published today in Neuron, scientists from the Salk Institute describe how neural regulation in the spinal cord differs for motor control of the arms vs the legs. These results could someday lead to stem-cell-based treatments for repairing spinal cord injuries.
The scientists focused on a group of neurons called V2a that express the gene CHX10, which are known to contribute to movement all along the spinal column. For the study, they wanted to find how these neurons differ at the cervical level where the arms are controlled versus the lumbar level where the legs are controlled. Using RNA sequencing they discovered that V2a neurons express CHX10 in different quauntities. In the cervical (arm) level approximately half the neurons express the gene and another half do not, whereas at the lumbar (leg) region most of the V2a neurons express it.
Next, they used optogenetics to see how the V2a neurons were connected to muscle-controlling neurons. They found that V2a neurons stimulated at the cervical level caused connections to motor neurons to be weak whereas in the lumbar region the connections were strong and quick. In a mouse model, the team used a technique in which a modified rabies virus traces neural circuitry to reveal that many of the V2a neurons that don’t express Chx10 in the cervical region were connected to the brain. The V2a neurons in the lumbar region were instead tightly connected to motor neurons and each other. This could explain the highly coordinated motion of hand and arm movement versus the more automatic motion of the legs.
The team plans to continue to refine their work and hope these findings can someday be used to create tailored treatments for repairing spinal cord injuries. "Right now, being able to use stem cells to repair spinal cord injuries is something we don't really know how to accomplish," says Samuel Pfaff, a Howard Hughes Medical Institute investigator at Salk and the study's senior author. "I use the analogy of trying to correct a problem with a car's electrical system by opening the hood and just throwing in a bunch of wires. With this work, we are one step closer to figuring out what all those different wires actually do."
Image: V2a neurons (smaller, faint blue) in the lumbar region of the spinal cord, shown alongside motor neurons (larger, bright blue). Image courtesy of the Salk Institute.