Researchers at the Albert Einstein College of Medicine of Yeshiva University have discovered the underlying cause of a type of ataxia, hereditary disorders characterized by poor balance, loss of posture and difficulty performing rapid coordinated movement.
Their work also led to a drug that significantly improved the motor coordination in mice with ataxia--a finding that could lead to better therapies for the disease. The study appears in the March issue of Nature Neuroscience and was featured in the publication's advance online edition.
The research, led by Dr. Kamran Khodakhah, associate professor in the department of neuroscience at Einstein, focused on a type of ataxia called episodic ataxia type-2. It results from gene mutations that affect calcium channels, which are involved in releasing neurotransmitters in the brain and regulating excitability in neurons. Episodic ataxia type-2 was thought to be due to impaired transmission of neurotransmitters, but the Einstein scientists suspected that something else was going on.
They studied specialized cells in the brain's cerebellum called Purkinje cells, which are rich in calcium channels. Purkinje cells help coordinate movement by acting as information clearinghouses: They take in sensory and other inputs relayed to them by more than 150,000 excitatory and inhibitory synaptic inputs, combine them with the cello's own intrinsic activity or "pacemaking," and then send out the signals necessary for motor coordination.
The researchers investigated whether ataxia might be due to a reduction in the precision of the intrinsic pacemaking by Purkinje cells. Studying a number of mouse models of ataxia type-2, they found a gene-dependent loss of the precision of pacemaking in Purkinje cells, which prevented them from accurately accounting for the strength and timing of synaptic inputs when sending out signals directing muscle movement.