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Parkinson’s is more complex than anyone thought, new research suggests

Stanford researchers set out to test a seminal theory of Parkinson’s disease and several related conditions. What they found is more complex than anyone had imagined.

Parkinson's disease affects millions of people worldwide, slowing their movements and making it difficult to walk, but exactly how Parkinson's works remains a bit mysterious. Now, Stanford researchers are challenging a seminal hypothesis of the disease known as the rate hypothesis.

"The idea was there was too much ‘stop’ and not enough ‘go’" in the brain circuits that stop and start movement, "and that's why there's difficulty with movement, said Mark Schnitzer, PhD, the study’s senior author and an associate professor of biology and of applied physics.

Schnitzer, research associate Jones Parker, Schnitzer’s former graduate student Jesse Marshall , PhD, and colleagues decided to test the rate hypothesis in healthy mice and mice with a Parkinson's-like condition, focusing on neurons in those mice's start and stop pathways. As I explain in a Stanford News story:

There were surprises almost immediately.

'We found all this undiscovered structure' in both pathways, Marshall said. Rather than all neurons in one or the other pathway lighting up at once, as the rate hypothesis would suggest, certain clusters seemed to be associated with certain activities. In healthy mice, a cluster in the start pathway might light up as a mouse began to turn left, while another in the stop pathway might light up when that mouse finished grooming its tail.

Mice with a Parkinson's-like condition had less activity in the start circuit, as the rate hypothesis suggested, but also lost all signs of structure in the stop circuit. Now, rather than send signals to terminate specific movements, the stop circuit suppressed many different movements at once.

L-dopa, a common Parkinson's drug, restored normal activity, but only at the right dose. Too high a dose, and L-dopa drove down activity in stop circuits and led to unstructured activity in start circuits, which may explain the jerky, uncontrolled movements that are a common side effect of the drug.

Photo by Benny Mazur

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