A recent discovery by a team of neuroscientists from McGill University may pave the way for novel therapies aimed at treating various psychiatric and neurological conditions linked to specific dopamine pathway malfunctions.
A recent discovery by a team of neuroscientists from McGill University may pave the way for novel therapies aimed at treating various psychiatric and neurological conditions linked to specific dopamine pathway malfunctions.
For individuals battling psychiatric issues like schizophrenia, addiction, or ADHD, and those facing neurological challenges such as Parkinson’s disease or Alzheimer’s, there seems to be promising news on the horizon. The researchers have found that a small cluster of dopamine neurons in the striatum is vital for maintaining essential brain functions, including reward processing, cognition, and movement coordination.
Dopamine is a key signaling molecule commonly associated with feelings of pleasure and rewards. However, it is also crucial for regulating mood, sleep patterns, and digestion, along with its roles in motor skills and cognitive activities. A surge of dopamine, often triggered by certain substances or behaviors, can contribute to addiction, while a deficiency can lead to significant issues with movement regulation, as seen in Parkinson’s disease.
A delicate balance
Previous research had demarcated the roles of two different dopamine pathways and receptor types in the forebrain: D1 receptors, which stimulate neurons, and D2 receptors, which inhibit them. A third category of receptors that combines both D1 and D2 receptor functions was acknowledged, yet its specific role had remained elusive until now.
Employing advanced genetic tools to target these dopamine receptors, which represent about five percent of the dopamine neurons in the striatum, the scientists began to unravel their functions.
The investigation revealed that these neurons showcase distinct cellular responses to dopamine and are crucial for a newly discovered pathway that is vital for the equilibrium of forebrain operations. This pathway is responsible for maintaining motor function under normal conditions and helps regulate excessive activity caused by stimulant drugs.
“Without these neurons, dopamine-controlled brain systems would become excessively active and uncontrollable because they help balance the functions of the two previously known dopamine receptor types that either enhance or inhibit activity,” explains Bruno Giros, a professor in McGill’s psychiatry department and a researcher at the Douglas Hospital Research Institute. He is the lead author of a recent study published in Nature Neuroscience. “This discovery is incredibly exciting for us as we have dedicated nearly 10 years on this specific research alongside a group at Université Libre de Bruxelles (ULB).”
Giros’s journey in this field spans 30 years, including collaborations with prominent neuroscientist Marc Caron and Nobel laureate Robert J. Lefkowitz as a postdoctoral fellow at Duke University Medical Center.
“We are still in the beginning stages of utilizing the tools we’ve created to identify this pathway,” says Alban de Kerchove d’Exaerde from ULB’s Neurophy Lab, who was part of the study. “I am confident that numerous labs will utilize our tools and, over time, uncover further insights into the crucial role this particular pathway plays across various domains,” Giros adds. “Now that we’ve grasped how this third pathway regulates motor functions, our next objective will be to delve deeper into how it influences cognitive processes and how this might be disrupted in psychiatric conditions.”
This research received funding from the Canadian Institute for Health Research (CIHR) and the Graham Boeckh Foundation.
