Janelia Research Campus
Dr. Hantman is a group leader at the Janelia Research Campus.
Central Control of Proprioceptive Signaling and Motor Output
A sailing connection initially drew Adam Hantman into the field of neuroscience, when he discovered that his future PhD adviser, Ed Perl at the University of North Carolina at Chapel Hill, also sailed a catboat.
"These are sailboats that you can sail by yourself into any inlet you want to go. They attract a certain type of person," says Hantman, who has applied that adventurous spirit to his research.
Perl championed the idea that neurons have a specific identity, transmitting specific messages, such as pain, within the nervous system. His ideas inspired Hantman. "The underlying thread in all of my research is exploring what a set of neurons is—how does the nervous system define them and use them to transmit information?" he says.
As a postdoctoral fellow, Hantman joined the lab of Thomas Jessell, an HHMI investigator at Columbia University and one of Perl's collaborators. There, he became interested in proprioception, what he calls "the mystical sixth sense," the sense that tells you where your body parts are in three-dimensional space.
Hantman wants to investigate how proprioception information travels from the body's periphery to the spinal cord and then how it is perceived by the higher brain. As a postdoc he studied Clarke's column, an area of the spinal cord that transmits signals from an animal's hindlimbs up to the brain, which then uses this information to coordinate movement.
While at Columbia, Hantman developed an in vitro preparation for the entire spinal cord including Clarke's column, with the sensory inputs and descending inputs coming from the brain's cortex all intact. He then used electrophysiology to test each of the components in the system. In this way, he was able to show that the cortical inputs from the brain could hijack the Clarke's column neurons, either exciting them in a similar way as sensory input would, or inhibiting them.
Hantman proposed that these cortical inputs were acting as corollary discharges—that is, copies of motor commands that stay within the central nervous system. Rather than the brain waiting hundreds of milliseconds for proprioceptive information to travel up to it, the excitatory corollary discharge may be used to build a prediction of movement to use as a guide. The inhibitory corollary discharge could suppress the flood of self-generated proprioceptive signals so the brain can easily distinguish normal movement from mistakes or external forces acting on a body part.
Although his work characterized that circuit in full detail, he was left with a nagging question: how does the circuit actually work in a living, moving animal? "It drove me bonkers for three years," says Hantman. "It was very unsatisfying to be left with a map, when I wanted to understand the function of the circuit."
At Janelia, Hantman wants to define what each of those components is doing in a whole animal: as sensory information comes in, how does it get transformed, what information gets passed along to the cerebellum, what is the cortical input really suppressing, how long does the suppression last?
He has changed his experimental setup so that he can electrophysiologically or optically record from a live mouse, and ultimately one that is awake and trained to make certain paw movements. Now, he's tracking the external cuneate nucleus (ECN), which coordinates proprioceptive information coming from and motor commands going to the mouse's forepaws. This will allow him to observe proprioceptive information as it comes into the ECN when the forepaw is moved into different positions and how this sensory information is integrated by the brain.
In another set of experiments, his group will gain control of the commands coming from the brain using optogenetics, in which a flash of light can activate or suppress a certain class of neurons in the system. Then the effects of these manipulations can be assessed by watching the circuit's behavior and the animal's reach. They may, for example, inactivate all of the inhibitory neurons in the system to ask what is the role of inhibition in proprioceptive processing.
Hantman loves being on the water for many of the same reasons he loves research. While his wife Kimberly and his dog Icon "both climb aboard and promptly fall asleep," he enjoys the solitary challenge of trying to account for all the ever-changing variables like wind, tide, currents, and other boats.
"Sailing is very similar to physiology—you have immediate readouts on real-time experiments. You have to be thinking actively online, considering as much as you can, and failing at being perfect. But the path there is so much fun and so stimulating."