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Thousands of our daily activities, from making coffee and taking a walk to saying hello to a neighbor, are made possible by an ancient collection of brain structures nestled near the center of the skull.
The cluster of neurons known as the basal ganglia is a central hub for the regulation of a wide range of routine motor and behavioral functions. But when signaling in the basal ganglia is weakened or broken, debilitating movements and psychiatric disorders can appear, including Parkinson’s disease, Tourette’s syndrome, attention deficit hyperactivity disorder (ADHD), and the disorder. obsessive compulsive.
Despite its central importance in controlling behavior, the specific and detailed pathways through which information travels from the basal ganglia to other regions of the brain have remained poorly drawn. Now, researchers at the University of California at San Diego, the Zuckerman Institute at Columbia University and their colleagues have generated an accurate map of brain connectivity from the largest output nucleus of the basal ganglia, a known area. under the name of substantia nigra pars reticulata, or SNr. The results offer an architectural plan of the region that revealed new details and a surprising level of influence linked to the basal ganglia.
The findings, led by project associate researcher Lauren McElvain and performed in the neurophysics lab of Professor David Kleinfeld at UC San Diego, and the lab of Zuckerman Institute principal investigator Rui Costa, are published on April 5 in the journal. Neuron.
The research establishes a new understanding of the position of the basal ganglia in the hierarchy of the motor system. The newly identified pathways emerging from the connectivity map, the researchers say, could potentially open up additional pathways for intervention in Parkinson’s disease and other disorders related to the basal ganglia.
“With the detailed circuit map in hand, we can now plan studies to identify the specific information carried by each pathway, how that information affects downstream neurons to control movement, and how dysfunction of each output pathway leads to various symptoms of basal ganglia disease, “McElvain said.
With support from NIH brain research through the Advancing Innovative Neurotechnologies® (BRAIN) initiative, researchers developed the new working model in mice by applying a set of modern neuroscience tools that combines techniques in genetics, virus tracing, automated microscopic imaging of whole brain anatomy and image processing. The results revealed surprising new insights into the extent of the connections.
“These findings are an example of how researchers supported by the BRAIN Initiative are using the latest brain mapping tools to fundamentally change our understanding of how connections in brain circuitry are organized,” said John J. Ngai, director of the NIH BRAIN Initiative.
Previous work had pointed out that the architecture of the basal ganglia is dominated by a closed loop with output projections connecting to the input structures. The new study reveals that SNr diffuses even at lower levels of the motor and behavioral system. This includes a large set of brainstem regions with direct connections to the spinal cord and motor nuclei that control muscles via a small number of intermediate connections.
“The new discoveries led by Dr McElvain offer an important lesson in motor control,” said Kleinfeld, a professor in the Division of Biological Sciences (Section of Neurobiology) and the Division of Physical Sciences (Department of Physics). “The brain does not control movement through a hierarchy of commands, like the ‘neural networks’ of self-driving cars, but through an intermediary management system that directs motive power while informing executive planners.”
Remarkably, according to the researchers, SNr neurons that project to the lower levels of the motor system have branching axons that simultaneously project to the brain regions responsible for higher-order control and learning. In this way, the newly described connectivity of SNr neurons fundamentally links operations across the high and low levels of the brain.
“The fact that output neurons from the basal ganglia project to specific brain nuclei downstream, but also diffuse this information to higher motor centers, has implications for how the brain chooses which movements to perform in a context. particular, and also on how he learns which actions in the future, ”said Costa, professor of neuroscience and neurology at Vagelos College of Physicians and Surgeons at Columbia, and director and CEO of the Zuckerman Institute.
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