Studies may lead to improved fine motor control and balance

Photo of Blazquez/Yakusheva lab team

The Blazquez/Yakusheva lab team (from left): Pablo Blazquez, PhD, Jaeryong Lee, Shintaro Miki, Fanetta Hampton, Rosenda Garcia Hernandez, PhD, Val Militchin, Tatyana Yakusheva, PhD, and Yutaka Hirata, EngD.

Diseases associated with motor control and balance represent the most common neurological disorders affecting the world today. To help fight this trend, Pablo Blazquez, PhD, and Tatyana Yakusheva, PhD, study the role of the cerebellum in motor control, balance and spatial navigation. They use a diverse array of experimental techniques, including measures of individual neuron activity, pharmacology, behavioral neuroscience, mouse genetics, immunohistochemistry, and computational modeling.

The cerebellum is located in the posterior portion of the brain, where it receives input from both brainstem and cerebral hemispheres.

The cerebellum plays an important role in motor control.  It utilizes input from all sensory systems and other parts of the brain and performs computations that are essential for skilled movements and balance. Two special regions of the cerebellum, the flocculus and the nodulus, are of particular interest to this team of investigators.

The flocculus plays an important role in our ability to maintain a fixed gaze during head movement, something known as the vestibular-ocular reflex or VOR. It does this by combining information from the vestibular system with eye movement-related information to create predictions of suitable corrective eye movements. “Our goal,” says Dr. Blazquez, “is to understand the neuronal computations performed by the different neuronal elements within the cerebellum during the performance of these oculomotor tasks.”

The nodulus plays a vital role in the control of balance and spatial navigation. It receives input from the vestibular portions of the inner ear and uses this information to make predictions of the body’s motion and orientation in space. The lab uses pharmacologic techniques to interrupt select neuronal circuits in order to identify their specific roles. A flight simulator-like motion apparatus, called a Moog system, allows the lab to activate any portion of the vestibular organs while recording neuronal responses to motion in 3D space. The lab then uses pharmacologic techniques to interrupt selected neuronal circuits to identify their specific roles.

Immunostained section of the cerebellar flocculus showing Purkinje cells labeled with antibodies to calbindin (blue) and molecular layer elements labeled with antibodies to GABA-B receptors (green).

The lab is currently supported by two NIH grants, and a variety of collaborations across the US and in Europe and Japan. A collaborative grant with Dr. Yutaka Hirata, head of the Neural Cybernetics laboratory at Chubu University College of Engineering in Japan, brings Japanese students every year to work in the lab. Other collaborators include Dr. Angel Pastor (Spain), Dr. Chris De Zeeuw (Netherlands), and Dr. Dora Angeloki (New York City).

A new collaboration with Aasef Shaikh, MD, PhD, at Cleveland Clinic in Cincinnati, is starting to yield some exciting results on how cerebellar circuits can be exploited to improve the treatment of patients with Parkinson’s disease. Two collaborative grant applications have resulted from this effort – the first, to study eye movements, has recently been submitted, and a second application to study motion/orientation perception is currently in preparation.