Genetics & Genomics Student Publication: Electrophysiological evidence of the role of the cerebellum in DYT1 dystonia.

Genetics and Genomics Graduate student Yuning Liu is the first author on a recent publication entitled “The abnormal firing of Purkinje cells in the knockin mouse model of DYT1 dystonia.”

Liu is in Dr. Yuqing Li’s lab which mainly focused on the pathophysiology and experimental therapeutics of DYT1 dystonia.

“DYT1 dystonia is an inherited movement disorder caused by a heterozygous trinucleotide deletion (GAG) in DYT1 gene,” Liu said.

Dystonia is a movement disorder in which your muscles contract involuntarily, causing repetitive or twisting movements. There is currently no cure for the disorder but many studies are being done for possible treatments.

“We previously reported altered structures in Purkinje cells and impaired motor control in Dyt1 KI mice, a disease mouse model of DYT1 dystonia,” Liu said. “In the current publication, we used the patch-clamp recording of Purkinje cells in brain slices and in acutely dissociated Purkinje cells to identify specific alterations of Purkinje cells firing. We found abnormal spontaneous firing of Purkinje cells, increased large-conductance calcium-activated potassium (BK) current, and increased BK channel protein level in Dyt1 KI mice. The results support the role of the cerebellum in the pathogenesis of DYT1 dystonia.”

When discussing the long-term implications of the study Liu stated that the findings may suggest a modulatory role of Purkinje cells in DYT1 dystonia pathogenesis. She also explained how this research may benefit people in the future with dystonia.

“Deep brain stimulation is a powerful treatment for DYT1 dystonia patients," Liu said. “However, there is also significant variability in outcomes for the patients. Future preclinical and clinical studies using optogenetics and/or chemogenetics techniques to manipulate Purkinje cells activity may have great promise to treat DYT1 dystonia patients.”

Purkinje Cell

Liu’s interest in neuroscience and the brain led her to this area of study.

“I’ve always wanted to study neuroscience,” Liu said. “The brain is a fascinating organ and is the most complex organ in the body. For example, researchers already know that mutation in DYT1 gene causes the DYT1 dystonia, but how three base-pair nucleotides deletion affect the brain and lead to such severe symptom is still unknown. Hopefully we can figure it out and find a cure in the end.”

Liu is planning to graduate from the Genetics and Genomics Graduate program in 2021 and stated that she is keeping her options open and considering a career in academia or industry.

For more information on dystonia and the research being done at UF visit UF Health’s movement disorder information page.