Two secrets of one of the brain’s most enigmatic regions have finally been revealed. In a pair of new studies, scientists from the Gladstone Institutes have discovered a specific neural circuit that controls walking, and they found that input to this circuit is disrupted in Parkinson’s disease.

Walking becomes a major challenge for people afflicted by Parkinson’s disease. Parkinson’s is caused by a depletion of dopamine–an important neurochemical–in the basal ganglia (BG), a brain region involved in fundamental behaviors like movement, learning, reward, and motivation. In Parkinson’s, an imbalance arises between two pathways in the BG: the direct or “go” pathway and the indirect or “stop” pathway. Ordinarily, these pathways work together seamlessly to control locomotion, but in Parkinson’s the stop pathway overpowers the go pathway, making it difficult to initiate movement. How the imbalance between these two pathways developed remained a mystery–until now.

Correcting an Imbalance in the Brain

Published in Neuron, scientists led by Gladstone associate investigator Anatol Kreitzer, PhD, discovered that dopamine depletion causes a miscommunication between the BG and another region called the thalamus, an area thought to relay sensory information to the brain. This miscommunication 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.

“This study provides strong evidence for a mechanism by which the stop pathway overcomes the go pathway in Parkinson’s disease,” says first author Philip Parker, PhD, a former graduate student in Dr. Kreitzer’s lab at the Gladstone Institutes and the University of California, San Francisco (UCSF). “Our findings implicate the thalamus in the development of the disease, an area of the brain that has received relatively little attention in Parkinson’s research.”

“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,” adds Dr. Kreitzer, who is also an associate professor of physiology and neurology at UCSF. “Our findings finally provide a clear picture of how the thalamus can imbalance neural circuits and suppress movement in this condition.”


Anatol C. Kreitzer et al. Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia. Cell, January 2016 DOI:10.1016/j.cell.2015.12.037

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The above post is reprinted from materials provided by Gladstone Institutes. The original item was written by Dana G. Smith, PhD. Note: Materials may be edited for content and length.

Gladstone Institutes. “Treating Parkinson’s disease by solving the mysteries of movement: Scientists discover a brain circuit that controls walking and identify a new target for treating Parkinson’s disease.”

Source: ScienceDaily. ScienceDaily, 28 January 2016. <>.