The basal ganglia connectivity map reveals key links with implications for a range of disorders
Thousands of our daily activities, from making coffee to walking to greeting a neighbor, are made possible by an ancient cluster of brain structures hidden away near the center of the skull.
A group of neurons known as the basal ganglia is a central hub for regulating a wide range of routine motor and behavioral functions. But when the signals in the basal ganglia weaken or break, movement disorders and psychiatric disorders can appear, including Parkinson’s disease, Tourette’s syndrome, attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder.
Despite their central importance in controlling behavior, the specific and detailed pathways through which information flows from the basal ganglia to other brain regions remained poorly planned. Now, researchers at the University of California San Diego and the Zuckerman Institute of Columbia University and their colleagues have created an accurate map of the brain’s connectivity from the largest nucleus resulting from the basal ganglia, an area known as the pars reticular material nucleus, or SNr. The results provide a blueprint for the region’s architecture that revealed new details and an astonishing level of influence associated with the basal ganglia.
The results, led by co-project scientist Lauren McLaughan and carried out in the neurophysics lab of Professor David Kleinfeld at the University of California, San Diego, and the Zuckerman Institute Principal Investigator’s Laboratory, Roy Costa, were published April 5 in the journal. Neuron.
The research establishes a new understanding of the position of the basal ganglia in the motor system hierarchy. According to the researchers, newly identified pathways emerging from the connection map likely open additional avenues for intervention in Parkinson’s disease and other disorders associated with the basal ganglia.
With the detailed circuit map in hand, we can now plan studies to determine the specific information that each pathway transmits, how this information affects downstream neurons to control movement and how the dysfunction in each output pathway leads to various symptoms of basal ganglia disease. McLaughan said.
Supported by Brain Research at the National Institutes of Health through the Advanced Innovative Neurotechnologies® (BRAIN) initiative, researchers have developed a new blueprint that works in mice by applying a modern neuroscience toolkit that combines techniques from genetics, virus tracking and automated microscopy to completely dissect the brain and Image processing. The results revealed surprising new insights into the breadth of communication.
“These findings are an example of how researchers supported by the Brain Initiative are using the latest brain mapping tools to change a fundamental way in our understanding of how connections are organized in brain circuits,” said John J. Ngay, director of the Center for Brain Research. BRAIN Initiative of the National Institutes of Health.
Previous work had emphasized that the structure of the base nodes is dominated by a closed loop with output projections that are again related to the input structures. The new study revealed that SNr transmits even lower levels of motor and system behavior. This includes a large group of brainstem regions with direct connections to the spinal cord and the motor core that control muscles through a small number of interconnections.
“The new findings led by Dr. McLevan provide an important lesson in motor control,” said Kleinfeld, professor in the Department of Biological Sciences (Department of Neuroscience) and Department of Physical Sciences (Department of Physics). “The brain does not control movement through a hierarchy of commands, such as the ‘neural networks’ of self-driving cars, but through a middle management scheme that directs engine production while informing operational planners.”
Remarkably, according to the researchers, SNR neurons that project at lower levels of the motor system have branching axons that simultaneously support the areas of the brain responsible for control and higher-level learning. In this way, the newly described communication of SNR neurons essentially connects processes across the high and low levels of the brain.
“ The fact that neurons from specific basal ganglia project into specific brain nuclei downstream, but also transmit this information to higher motor centers, has implications for how the brain chooses which movements to perform in a given context, as well as how it learns about The procedures must be said Costa, Professor of Neuroscience and Neuroscience at Vagelius College of Physicians and Surgeons in Colombia, as well as director and executive director of the Zuckerman Institute.
Contributors to the study include Byungkook Lim and Brenda Bloodgood at the University of California, San Diego, Geoffrey Moore at Harvard, Yongkong Chen at NEC Labs America and J Stefano Brigidi, who is currently at the University of Utah Medical School.
This work was supported by the European Research Council, the Howard Hughes Medical Institute, the National Institutes of Health (T32 NS007220, U19 NS107466, U01 NS090595, R01 NS111162 and U19 NS104649), the Tourette Association of America, and equipment boxes from Dr. George Fehr Chair in Experimental Biophysics.