Neuroscientists Find New Pathways

Carnegie Mellon University researchers have used next-generation viral tools to visualize previously undiscovered neural pathways. The work was published in the Journal of Neuroscience.

Aryn Gittis, a professor of biological sciences and a member of Carnegie Mellon's Neuroscience Institute, investigates how neural circuits control movement in humans and how to retrain those circuits after injury or damage. Among the areas Gittis' lab studies is the globus pallidus (GPe), a region of the brain implicated in regulating voluntary movement.

"This part of the brain that we're studying is always thought of in motor control, and that's it," Gittis said. "But it is also important for decision making and emotional memories. However there is no model for how its connectivity might account for these functions."

Through a new method involving fluorescent tracers, Gittis and Maxime Vounatsos, a Ph.D. student in the Department of Biological Sciences, labeled and differentiated target cells related to GPe and nearby structures with unprecedented specificity. Gittis said due to its extreme complexity, this part of the brain has been left unexplored because similar tasks were beyond the capacity of older techniques.

"By taking advantage of this technology, we were able to visualize neural pathways that had never before been discovered," she said.

The researchers found an unexpected connection to the GPe and structures involved with a variety of functions including movement, learning and emotion.

"It paints a pretty picture for some of these functions that we are trying to find where they come from," Vounatsos said. "The external segment of the globus pallidus has a lot of functions associated with it, both in the context of normal brain conditions as well as diseased brain conditions."

One connection of interest was projections from the GPe to the retrorubral field (RRF), a midbrain structure that produces dopamine.

"We found the projection while simply observing what brain areas receive the densest projections from the GPe," Gittis said. "The projection from the GPe to the RRF was quite striking, but when we looked in the literature, there was very little that had been written about it."

Gittis said that the pathways uncovered might be involved in helping animals determine how to behave in response to stimulate that induce fear or pain.

"Sometimes you want to ignore these cues and power through, but sometimes you want to pay attention to these cues and change your behavior," Gittis said. "We think the pathways we've uncovered might be involved in this decision-making process."

Vounatsos said they plan to further investigate the disynaptic connections of the GPe through the RRF and how these circuits relate to behavior.

"We plan to see how these circuits affect behavior," Vounatsos said. "We want to see how each component of the GPe projection to the RRF is active or inactive during specific behaviors."

Their work received funding from the National Institutes of Health.