New research by a Virginia Tech neuroscientist at VTC’s Fralin Biomedical Research Institute is raising questions about a long-standing approach to studying chronic neurological conditions such as dystonia, ataxia and tremors.
These disorders are caused by problems in the cerebellum, a region of the brain involved in the coordination of movement. When the cerebellum is disturbed, people may experience symptoms including painful muscle contractions, abnormal postures, and uncontrollable tremors.
For years, neuroscientists have focused on the relationship between two types of brain cells in the cerebellum. One group, known as Purkinje cells, suppresses the activity of another group called cells of the deep cerebellar nuclei. Because of this connection, researchers have generally assumed that observing Purkinje cell activity provides a reliable picture of what happens in deep nucleus cells.
A new study led by Meike van der Heijden suggests that assumption may not be true.
Published in the Physiology MagazineThe research found that activity in one cell type does not reliably predict activity in the other, despite their direct anatomical connection.
“We see that there is no clear linear relationship between the activity of Purkinje cells and those of the deep nuclei. Therefore, there is very limited predictive power in monitoring one to understand what is happening in the other,” said Van der Heijden, an assistant professor at the institute.
Implications for dystonia, ataxia and tremor
The findings could have important implications for both research and treatment of cerebellar movement disorders.
“The activity of Purkinje cells and the deep nuclei of the cerebellum is altered in a pathological state, and a better understanding of the relationship between these types of neurons will ultimately help optimize treatments for diseases such as dystonia, ataxia and tremor,” said Alyssa Lyon, a doctoral candidate in Virginia Tech’s Translational Biology, Medicine and Health Graduate Program and first author of the paper.
One of the reasons Purkinje cells have received so much attention is that they are easier to study. They are located in the outer layer of the cerebellum, making them more accessible to researchers. Deep nucleus cells, on the other hand, are located further below the surface of the brain and are more difficult to measure directly.
As a result, many scientists have treated Purkinje cell activity as a useful biomarker of what is happening in deeper cells.
Unexpected results of cerebellar recordings
Under normal circumstances, Purkinje cells inhibit cells in the deep nuclei. Based on that relationship, higher activity in Purkinje cells would be expected to correspond with lower activity in cells in the deep nuclei, while reduced Purkinje activity would be expected to have the opposite effect.
To test that assumption, the research team analyzed a database of electrophysiological recordings collected from preclinical models of cerebellar disease.
The results revealed no significant correlation between activity in the two cell populations.
“We suggest that if you want to know how the cerebellum behaves in a disease state, you have to look at the deep nuclei of neurons, not just the Purkinje cells,” said Van der Heijden, who also holds a position in the School of Neuroscience at Virginia Tech.
He added that researchers should also be wary of treatment strategies that focus on altering Purkinje cell activity with the expectation that cells in the deep nuclei will respond accordingly.
“This is a cautionary tale for understanding cerebellar activity in diseases, but also for treating these challenging diseases,” Van der Heijden said. “We need to be very careful in making assumptions and doing experiments to test our hypotheses.”