Study Clarifies The Neurological Process That Makes Walking Possible, Makes Strides Toward Better Paralysis Treatments

Columbia University Health Sciences
Wednesday, 2 June 2004

A Columbia-led team of investigators, working in collaboration with researchers at the Salk Institute, have come up with a method to distinguish between the neurons in the spinal cord that control coordination of ambulatory movements between the left and right limbs. These findings may shed light on the neurological mechanisms that underlie a person's ability to walk -and may have potential implications for the development of new treatments for paralysis. The research was published in the May 13 issue of the journal Neuron.

In prior studies, Columbia researchers--led by Alessandra Pierani, Ph.D., former postdoctoral research fellow, and Thomas Jessell, Ph.D., professor of biochemistry and molecular biophysics--had determined that a particular set of interneurons, called V0 interneurons, require a genetic switch called Dbx1 to assume their identity. They showed in mouse models that the Dbx1 neurons arose on one side of the spinal cord but crossed to the other side to connect to motor neurons. The investigators deduced that this type of wiring would be characteristic of the neural circuitry that controls left-right locomotion.

To determine whether such V0 interneurons actually contribute to left-right locomotion, the Columbia group, led by Dr. Jessell, teamed up with Dr. Martyn Goulding's lab at the Salk Institute to perform electrophysiological studies on the spinal cords of both normal mice and mice lacking Dbx1. They found that the mice with Dbx1 demonstrated standard left-right patterns in locomotion, but those without the genetic switch were unable to coordinate their walking, using both limbs simultaneously.

"This technique represents a small step toward understanding the logic of spinal locomotor control. Once we understand that logic, we should in principle have a better insight into how to manipulate the damaged spinal cord in a way that restores function," said Dr. Jessell.

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