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Getting a grip on hand function

Discovering key spinal cord circuits

- April 11, 2013

Drs. Rob Brownstone and Tuan Bui. (Provided photo)
Drs. Rob Brownstone and Tuan Bui. (Provided photo)

Professor and neurosurgeon Dr. Rob Brownstone and postdoctoral fellow Dr. Tuan Bui have identified the spinal cord circuit that controls the hands’ ability to grasp.

The world’s leading neuroscience journal, Neuron, published the breakthrough finding in its latest issue.

The researchers have found that a certain population of neurons in the spinal cord — called the dI3 interneurons — assess information from sensory neurons in the hands and then send the appropriate signals to motor neurons in the spinal cord, and hence to the muscles, to control the hands’ grip.

Importance of hand-grip control


“This circuit allows us to subtly and unconsciously adjust our grasp so we apply the right amount of force to whatever we’re holding,” says Dr. Brownstone, a professor in the Department of Medical Neurosciences and the Division of Neurosurgery. “This mechanism is disrupted in spinal cord injuries, which can completely eliminate the ability to grasp, and in neurodegenerative diseases like Alzheimer’s disease, which can lead to an uncontrollable reflexive grasp such that people grab and can’t let go of what they touch.”

Impaired hand function has a devastating effect on people’s independence and ability to function in daily life. As Dr. Brownstone points out, people with quadriplegia ranked hand function as their number-one priority, when asked in a 2004 survey which function they would most want to recover if they could. They rated hand function well above trunk stability, walking, sexual function, bladder and bowel control, and normal sensation.

An unexpected finding


Drs. Brownstone and Bui were testing a spinal cord circuit for its role in the rhythmic pattern of walking, when they found it controlled hand grip instead. “The mice with this circuit disrupted were walking just fine, but I found it was unusually easy to remove them from their cages,” recounts Dr. Bui. “Mice will usually grab onto the cage wires when you go take them out, so this really got us thinking.”

While Dr. Bui was pondering the meaning of this unexpected observation in the lab, Dr. Brownstone was in his neurosurgery clinic, assessing a patient who was unable to control her grasp. “When she took my hand, she was unable to let go,” he recalls. “I had to peel her fingers off one by one to release my hand.”

As they compared notes, Drs. Brownstone and Dr. Bui quickly realized they had come across the circuit that controls hand grasp. Struck by the implications of their observations, they embarked on a series of experiments — with collaborators, including Dr. Tom Jessell at Columbia University in New York City — which validated the finding.

A path to future treatments


Now that the researchers have identified the specific spinal cord circuit that controls hand grip, they can go on to find targets for potential treatments for impaired hand function. “It’s possible that a neurotransmitter or other agent could be delivered to the spinal cord to correct the faulty circuit,” notes Dr. Brownstone. “It could be a complex strategy, but understanding is always the first step.”

Dr. Brownstone is a Tier 1 Canada Research Chair in spinal cord circuits. His research is also supported through grants from the Canadian Institutes of Health Research. Dr. Bui is a key member of Dr. Brownstone’s research team in the Motor Control Lab at pilipiliÂţ»­, where they are identifying the neural circuits that control our ability to walk and move in coordinated ways. Their ultimate goal is to identify targets for therapies to restore lost motor function and control in people with spinal cord injuries and other neurological diseases.