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Home » New Group of Neurons Implicated in Parkinson’s Disease
Disease Discoveries

New Group of Neurons Implicated in Parkinson’s Disease

By Will DossFeb 25, 2019
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D. James Surmeier, chair and Nathan Smith Davis Professor of Physiology, was senior author of the study published in Neuron.

Abnormal activation of a small population of neurons may contribute to motor learning and motor function deficits in patients with Parkinson’s disease, according to a recent Northwestern Medicine study published in the journal Neuron.

“Understanding how something works gives you confidence that you can fix it when it breaks,” said D. James Surmeier, PhD, chair and Nathan Smith Davis Professor of Physiology, and senior author of the study. “By providing this new level of understanding of the circuitry, we hope to motivate the effort to develop new therapies for Parkinson’s disease.”

Parkinson’s disease (PD) is characterized by degeneration of dopamine neurons in the basal ganglia, a brain region responsible for goal-directed and habitual movement. The basal ganglia receives neural signaling primarily from the cerebral cortex, but another major input is from the intralaminar thalamus, a region of the thalamus that is activated in humans by arousing events, according to Surmeier.

“When something salient happens in the environment — a loud noise or a flash, for example — you want to orient to it and figure out what’s going on before you continue what you were doing,” Surmeier said. “The intralaminar thalamus fires you up and gets you ready when something important happens in the environment.”

The pathway from the intralaminar thalamus to the basal ganglia has two channels: a “go” channel that promotes actions, and a “stop” channel that suppresses actions. Normally, these two channels work together to help individuals do the right thing at the right time, Surmeier explained.

The scientists investigated both pathways, searching for differences between normal mice and mice models of PD.

They found that in PD models, the thalamus abnormally activated cholinergic interneurons in a basal ganglia region called the striatum, leading to amplification of the “stop” channel.

“This the first time the thalamus was implicated in PD symptoms,” Surmeier said. “Normally, the ‘stop’ channel has to work in coordination with the ‘go’ pathway, but in Parkinson’s disease, it is hyper-activated — there’s a constant stop signal.”

This amplification appears to contribute to both general movement deficits in patients with PD as well as their difficulty in learning new tasks, Surmeier said.

“It leads to slowness and difficulty initiating movement because it is saying stop, wait, something important has happened,” Surmeier said. “It also disrupts learning, because it is constantly telling the basal ganglia circuitry to change, rather than allowing actions that achieved their goal to be repeated.”

Furthermore, they discovered the amplification was mediated by nicotinic receptors, providing insight into why smoking cigarettes seems to alleviate symptoms in patients with PD.

“This study helps us understand why smoking tobacco might diminish the symptoms of Parkinson’s disease, but the risks associated with tobacco use outweigh the potential benefits,” Surmeier said.

The scientists experimented with suppressing this signaling pathway, finding that while it didn’t improve motor coordination in mouse models of PD, their ability to learn was dramatically improved. This could conceivably be applied to human patients, Surmeier said.

“I don’t know of any other strategy that improves the ability of Parkinson’s patients to learn new things,” Surmeier said. “This was one of the most fascinating outcomes of the study.”

This work was supported by a Parkinson’s Disease Foundation Fellowship, Flanagan Fellowship, and grants from the JPB Foundation, the IDP Foundation, and National Institutes of Health grants NS 34696 and NS 54850.

Asami Tanimura, PhD, a postdoctoral fellow in the Surmeier laboratory, was senior author of the study. Feinberg co-authors included Surmeier laboratory members Yijuan Du, PhD, a postdoctoral fellow, and Jyothisri Kondapalli, PhD and David Wokosin, PhD, both research assistant professors of Physiology.

Neurology and Neuroscience Physiology Research
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