When University of Minnesota basic neuroscientist Timothy Ebner, M.D., Ph.D., began researching how episodic ataxia changes brain cells‚ the results were illuminating.
Ebner‚ head of the University’s Department of Neuroscience and holder of the Visscher Chair in Physiology‚ received a one-year‚ $75‚000 grant from the Bob Allison Ataxia Research Center (BAARC) to use a technology called optical imaging to learn more about why episodic ataxia creates temporary bouts of debilitating symptoms.
“We know that patients with episodic ataxia have periods of loss of motor coordination and difficulty balancing that are caused by a dysfunction in the cerebellum‚ but for the longest time‚ no one understood why they would be sick for only 30 or 40 minutes at a time and then basically return to normal functioning‚” says Ebner‚ who studies how brain cells function both in healthy brains and brains afflicted by neurodegenerative diseases. “Our team wanted to find out what made the disease’s symptoms so temporary‚ so transient.”
Researchers knew that caffeine‚ stress‚ and alcohol could trigger symptoms in people with episodic ataxia type 2‚ so Ebner’s team used caffeine to produce similar temporary symptoms in mice with the disease. Then the team used a new technique that monitors light signals generated by brain-cell activity and “circuits” that were principally involved in the episodic ataxia attack.
Almost immediately‚ one of Ebner’s associates detected an abnormality. “We found that certain neurons in the cerebellum were oscillating—meaning that they were firing in a rhythmic pattern so powerful that they could not respond to any other normal brain signals‚” Ebner says.
Within a few minutes‚ the oscillations started to expand to other regions of the cerebellum and were associated with abnormal movements that spread throughout the mouse’s body. “For as long as the oscillations occurred‚ the symptoms continued‚” Ebner says‚ “but when the oscillations stopped‚ so did the dysfunction.”
To Harry Orr, Ph.D., a lead ataxia researcher at the University‚ Ebner’s findings are exciting. “Tim was very successful in demonstrating what might actually be causing episodic ataxia‚” Orr says. “The notion that his findings could accurately reflect the disease process in humans makes his research that much more valuable.”
Ebner knows he’s still got work to do. “Now that we have found these oscillations‚ we think we understand the reason that the dysfunction in the cerebellum can be temporary‚” he says. “But now we have millions of questions about why this happens.”
Among them: Does this same exact mechanism occur in humans with episodic ataxia type 2? How do the oscillations spread to other parts of the brain and nervous system? How can the oscillations be controlled?
Ebner hopes to answer those questions soon; he’s using the preliminary data his team has gathered to apply for larger grants to continue the work.
Optical imaging technology purchased by the BAARC board two years ago played a major role in advancing this research‚ Ebner says.
“Actually visualizing the activity of the brain cells in the intact cerebellum is what makes the work so promising‚” Ebner says. “If we were using any of the other traditional techniques—like electrophysiology—we never would have known where to look or have found the oscillations.”