A pair of recent studies suggests that a specific circuit in the brain controls walking, and that input to this circuit may be disrupted in Parkinson’s disease.
In the first study, published in Neuron, scientist from the Gladstone Institutes, led by associate investigator Anatol Kreitzer, PhD, suggests that the depletion of dopamine in the brain’s basal ganglia (BG) region—which researchers suggest causes Parkinson’s to develop—causes a miscommunication between the BG and the thalamus, through which scientists believe sensory information is relayed to the brain.
In Parkinson’s, an imbalance arises between two pathways in the BG that control locomotion: the direct or “go” pathway and the indirect or “stop” pathway. The miscommunication resulting from the depletion of dopamine results in a loss of input to the “go” pathway from the thalamus, which consequently disrupts movement.
Blocking the connection between the two regions reversed the imbalance between the “stop” and “go” pathways, and restored normal behavior in a mouse model of Parkinson’s, explains a media release from Gladstone Institutes.
“Several studies have targeted the thalamus with deep brain stimulation to treat Parkinson’s, but the region’s role in the disease was not well established,” says Kreitzer, who is also an associate professor of physiology and neurology at University of California San Francisco. “Our findings finally provide a clear picture of how the thalamus can imbalance neural circuits and suppress movement in this condition.”
In the second study, published in Cell, scientists from Gladstones Institutes, led by Dr Kreitzer, note that the “go” and “stop” pathways from the BG control locomotion by regulating a group of nerve cells in the brainstem that connects the brain to the spinal cord. The “go” pathway selectively activates a type of neuron in the brainstem that releases the neurochemical glutamate, and these neurons are responsible for triggering locomotion, the release explains.
By using optogenetics, the scientists stimulated either the “go” or the “stop” pathway in mice that were running on a treadmill, while recording neural activity in the brainstem. They discovered that the “go” pathway selectively activated glutamate neurons, causing the mice to move, whereas the “stop” pathway inhibited these neurons and made the mice stop.
During the study, they also observed from the mice activity that the brainstem neurons can overpower the signals from the BG—that is, if glutamate neurons were turned on, the animal moved even if the stop pathway is activated, the release continues.
“In order to understand why walking is particularly disrupted in Parkinson’s disease, we need to map out the circuitry that controls walking,” Kreitzer states in the release.
“Our study shows that a specific set of neurons in the brainstem are both necessary and sufficient to initiate locomotion. This finding could open the door for new treatment targets to help Parkinson’s patients walk more easily,” he adds.
[Source(s): Gladstone Institutes, Newswise]
