By GREGORY ZELLER //
A new Stony Brook University study digs deep into the cerebral cortex to discover fresh clues about declining motor skills in Parkinson’s disease patients.
The loss of neurons (brain-based nerve cells) and dopamine (brain-based neurotransmitters) has been well-documented by scientists studying the dreaded nervous-system disorder. But exactly how this “dopaminergic modulation” affects motor skills is unclear, prompting researchers in the Renaissance School of Medicine’s Department of Neurobiology and Behavior to consult an experimental model, designed to mimic a motor cortex in decline.
Their findings – published in September in eNeuro, the Society for Neuroscience’s peer-reviewed journal – support an entirely new line of research regarding reduced dopamine signaling. Neurobiology and Behavior Professor Arianna Maffei, one of three authors listed on the eNeuro paper, said the biggest takeaway is that reduced dopamine distribution might not actually be the primary cause of motor-function decline in Parkinson’s patients.
“Our study shows that the changes in excitability of motor-cortex neurons very likely are due to basal ganglia pathology, and not loss of direct dopaminergic innervation of the motor cortex,” Maffei said.
Arianna Maffei: Brain matters.
For non-neurobiologists: The basal ganglia (nuclei buried deep in the brains of vertebrates) are sick, and that’s what causes declining motor skills – not the loss of dopamine neurotransmitters.
That’s not to say the loss of neurons and dopamine, long associated with Parkinson’s, isn’t critically important; on the contrary, the study “supports the idea that changes in motor-cortex activity due to loss of dopamine are very important for the pathophysiology of PD,” Maffei noted.
But the three-part experimental model – which pharmacologically blocked carefully selected motor-cortex receptors, then poisoned dopaminergic neurons in the midbrain (to mess with the basal ganglia), then killed off dopamine neuron axons (itty bitty intra-neuron connectors) in the motor cortex – shed new light on precisely how the dopamine decline affects the motor cortex’s input/output functions.
In a nutshell: The dopamine drop doesn’t directly cause the abnormal motor cortex functions, but it damages the basal ganglia nuclei – which does cause the dysfunction.
Ultimately, the notion that acute or chronic loss of dopamine signaling has such profound effects on motor-cortex neurons demands additional research into the possibility of the motor cortex as an intervention site for new Parkinson’s treatments, according to Maffei and research partners Olivia Swanson, a 2020 Stony Brook PhD and University of Pennsylvania electrophysiologist, and Rosa Semaan, currently a student at New York Medical College in upstate Valhalla.
“This adds to our current knowledge and points to the motor cortex as a potential novel site for intervention,” Maffei added.
