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Martyn D. Goulding

 

Martyn D. Goulding

Martyn D. Goulding

Professor
Molecular Neurobiology Laboratory

"We are focusing our efforts on how different types of spinal cord 'interneurons'—neurons that bridge communications between sensory and motor neurons—control how we move and how we respond to touch and pain. Knowing more about how these cells develop and function is a critical step in devising new therapies to regenerate and activate circuits in the spinal cord following injury."

The muscle contractions that allow us to move about generally show a rhythmic pattern of activity. Central pattern generators (CPGs)—specialized networks of neurons in the spinal cord—function as control and command centers for these rhythmic movements. Remarkably, this circuitry can operate without any input from the brain, which explains why headless chickens run away from the butcher's block. Although researchers have known about CPGs for many years, identifying the nerve cells that make up these circuits had proved to be very difficult. Even on closer inspection, the spinal cord just appeared like a jumbled mass of hundreds of thousands of neurons that all looked the same.

The Goulding laboratory has been at the vanguard of efforts to break the molecular code that specifies different groups of interneurons in the spinal cord. In so doing, they have begun to unravel the wiring of the spinal cord so as to ascertain how the locomotor CPG functions. Interneurons, like all other neurons in the brain and spinal cord, come in two flavors, excitatory neurons that transmit and amplify signals, and inhibitory neurons that inhibit and refine those signals. In earlier studies, Goulding and his team discovered that a subset of inhibitory interneurons, called V0, govern left-right alternation, while V1 neurons, also inhibitory, control the speed at which leg muscles contract and relax and thus set the pace. While alternating leg muscle contractions between the left and right side and controlling the speed are crucial, it is just as important to ensure that the intensity and duration of the muscle activity in each limb is symmetrical to achieve a stable and balanced walking rhythm. Recent experiments have now revealed that a group of excitatory interneurons, the V3 neurons, are in charge of balancing rhythmic activity between the left and right side of the body. Without them, mice have great difficulty walking and show an ataxic gait.

Knowing which neurons are part of the locomotor CPG and how they control the essential aspects of walking will put researchers in a better position to design treatments or implants for spinal cord injuries that restore or activate these pathways.

Lab Photo

Left to right:
Eric Geiman, Timothy Wong, Martyn Goulding, Olivier Britz, Ying Zhang, Marta Garcia del Barrio, Kelsey Theriault, Floor Stam, Tomoko Velasquez, Timothy Hendricks, Jingming Zhang, and Christopher Padilla

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Martyn D. Goulding

Faculty

Martyn D. Goulding

Martyn D. Goulding

Professor
Molecular Neurobiology Laboratory

Martyn D. Goulding, a professor in the Molecular Neurobiology Laboratory, studies the early development of the nervous system. He focuses on how interneurons, responsible for communication between nerve cells in the spinal cord, and motor neurons, which cause muscles to contract, are generated in the embryonic spinal cord. Knowing more about how these cells form will further understanding of how to regenerate and reconnect the many types of nerve cells that are necessary for moving our muscles.

His lab studies a family of genes known as the Pax genes. They have discovered that one of its members, Pax-3, determines which cells will become part of the spinal cord. A significant indication of the gene's importance has been the identification of Pax-3 mutations in a human disorder called Waardenburg Syndrome. Further knowledge of how Pax-3 functions should provide important insights into other birth defects, including exencephaly and spina bifida.

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