A UCLA STUDY USING MICE reveals new insights into the wiring of a major circuit in the brain that is attacked by Parkinson’s and Huntington’s diseases. The f indings, based on research conducted by UCLA scientists as part of the nat ional BRAIN Initiative Cell Consensus Network, could shape future understanding of how diseases arise in the human brain and pinpoint new targets for treatment. UCLA scientists have been conducting a comprehensive analysis of how the mouse brain is wired. Their research has thus far analyzed 600 pathways and catalogued nerve-cell connectivity to create a wiring diagram of critical brain circuits. “Like any explorer traveling deep into uncharted territory, we make maps to guide future visitors,” says Hong-Wei Dong, MD, PhD, professor of neurobiology. “My lab mapped out the intricate circuitry of the mouse brain to enable other scientists to conduct more accurate exper iment s in mouse models of diseases like Parkinson’s or Huntington’s disease.”
Using a green dye, the UCLA scientists labeled a small number of individual neurons and tracked their connections with other neurons through arm-like projections called axons and dendrites . Those connections, called circuits, process and communicate distinct types of sensory information in the brain.
The researchers were particularly interested in the cortico-basal ganglia-thalamic loop, a crucial neural circuit that links regions in the brain that regulate movement, emotions and complex cognitive processes like learning and memory. The loop is affected by neurodegenerative disorders like Parkinson’s and Huntington’s diseases.
“We identified smaller circuits within the corticobasal ganglia-thalamic loop that process information for specific functions,” says Nicholas Foster, PhD, a project scientist in Dr. Dong’s lab. “Some of these subcircuits enable the brain to control movement of the arms, legs and mouth. Other circuits process emotional input or complex cognitive processes, such as learning the consequences of actions.”
The research gives scientists a baseline for what normal brain wiring looks like and pinpoints smaller circuits that could go awry when neurological diseases progress. “These subcircuits could reveal new treatment targets and serve as physiological benchmarks to measure the effectiveness of new drug treatments in preclinical experiments,” Dr. Foster says. When researchers detect shortened axons and dendrites in the neurons of a particular circuit in a mouse with a certain disease, for example, they can observe where the disease is having an effect. And if scientists administer treatment to the mice and see axons and dendrites developing normally in that area, they can surmise that the treatment is effective.
“Our results illuminate clearer paths for future studies to follow by illustrating how different brain structures organize into networks and communicate with one another,” Dr. Dong says. “These findings will enable scientists to better understand how dysfunction in one small brain region can undermine the function of its larger neural circuit.”
— Elaine Schmidt
“The Mouse Cortico-Basal Ganglia-Thalamic Network,” Nature, October 6, 2021