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Dysfunction in cerebellar Calcium channel causes motor disorders and epilepsy

that disturbing the output signals of the cerebellum is sufficient to cause the major disease phenotypes associated with the P/Q-type channel. In other words, P/Q-type channel mutations in the cerebellum alone can elicit a range of diseases, even when the same channels in other brain regions are intact.

Disturbing the input to the cerebellum has similar effects as disturbing the output

Mark's team has now found further evidence for this hypothesis. In the present study, the biologists did not disturb the output signals, i.e., the Purkinje cells, directly, but rather the input to these cells. The Purkinje cells are modulated by signals from other neurons, amongst others from the granule cells. "This modulatory input to the Purkinje cells is important for the proper communication between neurons in the cerebellum," Melanie Mark explains. In mice, the researchers disturbed the input signals by genetically altering the granule cells so that they did not express the P/Q-type channel. Like disturbing the cerebellar output in the 2011 study, this manipulation resulted in ataxia, dyskinesia, and absence epilepsy. "The results provide additional evidence that the cerebellum is involved in initiating and/or propagating neurological deficits", Mark sums up. "They also provide an animal model for identifying the specific pathways and molecules in the cerebellum responsible for causing these human diseases."


Contact: Dr. Melanie Mark
Ruhr-University Bochum

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