A team of neuroscientists led by researchers from McGill University in Canada has discovered what could open the door to new treatments for a range of psychiatric and neurological disorders attributed to dysfunction of dopamine pathways.
Scientists have discovered that a small group of dopamine neurons plays a crucial role in balancing many essential functions in the brain, including those related to reward, perception and movement. This holds hope for patients with psychiatric disorders such as schizophrenia, addiction or attention deficit hyperactivity disorder, or neurological disorders such as Parkinson’s disease or Alzheimer’s disease.
critical balance
Dopamine is a chemical molecule that acts as a neurotransmitter in the brain and is often associated with pleasure and reward. But it plays an equally important role in regulating mood, sleep, and digestion, as well as motor and cognitive functions. Excess dopamine, caused by certain drugs or behaviors, is responsible for addiction. Conversely, its absence can cause dramatic changes in motor control, as in Parkinson’s disease.
Scientists had previously identified the functions of two distinct pathways and two types of dopamine receptors in the forebrain: D1 receptors, which activate neurons, and D2 receptors, which inhibit them. A third group of dopamine receptors was known to exist, possessing both D1 and D2 receptors, but until now, no one had been able to pinpoint their exact function.
Innovative tools
Using innovative genetic tools to precisely target these receptors—which make up just 5 percent of dopamine neurons in the striatum—the researchers are beginning to understand their functions.
The researchers discovered that this group of neurons exhibits unique cellular properties in response to dopamine and is at the origin of a new pathway essential for the homeostasis of forebrain function. This pathway ensures movement control under normal physiological conditions and limits hyperactivity caused by stimulant drugs. The findings were published in Nature Neuroscience on July 4.
“Without these neurons, the brain systems that are under the control of dopamine would become overactive and out of control, because they balance the functions of the two types of dopamine receptors in the brain, which facilitate or inhibit the activation of the two pathways that we previously knew about,” explains Bruno Giros, lead author of the study, professor in the Department of Psychiatry at McGill University and researcher at the Douglas Research Institute.
“It’s a very exciting discovery for us, because we’ve been working on this specific project for nearly 10 years in collaboration with a team at the Université Libre de Bruxelles,” he added, according to EurekAlert.
“We are just beginning to work with the tools we have developed to help us identify this pathway,” says Alban de Kerchove d’Exerd of the Université Libre de Bruxelles, who participated in the research.
“I’m sure many labs will work with our tools and over time will discover more about the important role this very specific pathway plays in a variety of domains,” adds Giros. “Now that we understand how this third pathway controls motor function, the next goal of our research will be to better understand how this pathway is involved in controlling cognitive processes, and how it might be dysfunctional in psychiatric disorders.”