Dopamine causes brain cells to enhance the activity of neurons

Typically, the influence of dopamine on movement control is primarily associated with the striatum — a region of the brain where this neurotransmitter regulates signal transmission. A new study shows that the effect of dopamine is not limited to this area. It also plays an important role in another region — the substantia nigra, or more precisely, in its part called the “pars reticulata” (SNr). It is here that dopamine, acting through astrocytes, changes the way neurons involved in movement organization function.

Experiments were conducted on slices of mouse brain tissue, studying how dopamine affects the interaction of cells in the basal ganglia — a network of brain structures that are critically important for movement control and are severely affected in Parkinson’s disease. Optogenetic methods and electrophysiological recordings were used: this made it possible to accurately track how cell activity changes under the influence of dopamine.

Initially, the team wanted to confirm established ideas about the effect of dopamine on inhibitory signals in the brain. According to the classical model, dopamine promotes movement, in part by suppressing the activity of SNr neurons. However, a recent study found, on the contrary, that activation of dopamine receptors leads to an increase in the firing rate of these neurons, meaning they become more active.

The mechanism turned out to be linked to another neurotransmitter, GABA (gamma‑aminobutyric acid), which usually performs an inhibitory function. It turned out that dopamine stimulates astrocytes to more actively uptake GABA from the intercellular space. As a result, the level of inhibition decreases, and SNr neurons are able to generate impulses more frequently. At the same time, some GABA is released by the dopamine‑producing neurons themselves, while astrocytes regulate how much of this substance remains in the surrounding area and how long it remains active.

Another unexpected discovery concerns the very nature of how dopamine neurons function. It turned out that the GABA synthesized inside these cells can be used not only as a signaling substance but also as an alternative source of energy. As energy demands increase, a neuron can burn GABA in its mitochondria, effectively using it as fuel. The amount of GABA released in this process reflects the current metabolic state of dopamine cells.

These results are important not only for fundamental science but also for understanding Parkinson’s disease. Its symptoms arise due to the death of dopamine neurons, but an increasing amount of evidence suggests that dopamine loss alone in the striatum is not sufficient to explain all the disorders. The study highlights the importance of dopamine signaling specifically in the SNr region and shows that the mechanisms of movement control are more complex than previously thought.

Current and developing treatment methods (including gene therapy) are mainly aimed at restoring dopamine function in the striatum. New data suggest that targeting the SNr may also be beneficial. Moreover, this region is significantly smaller in volume, so targeted intervention in it is potentially technically simpler.

The main value of the work lies in the fact that it requires a revision of existing models of how the basal ganglia and dopamine control movement. Although additional research will be needed to translate these findings into actual treatment methods, the data obtained provide a new basis for understanding how dopamine shapes movement and what is disrupted in these processes in Parkinson’s disease.