Dr. Bruno Giros identifies a new dopamine pathway that may have implications in neurological and psychiatric conditions

July 4, 2024

Dopamine is a neurotransmitter that controls the brain’s pleasure and reward systems, as well as our ability to move, learn and pay attention. Until now, it has been thought that there were just two dopamine-related pathways in the brain. But after almost eight years of work, Dr. Bruno Giros and his team, working in collaboration with l’Université Libre de Belgique, has identified a third, hitherto unknown, communication pathway for dopamine. This could have important implications in both neurological (e.g. Parkinson’s and Alzheimer’s) and psychiatric (e.g. addiction, schizophrenia, etc.) conditions.

The international team’s findings were been published in Nature Neuroscience on July 4, 2024.


The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops.


“Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs”
by Patricia Bonnavion et al., published in Nature Neuroscience