Striatal dopamine reinforces activity patterns in cortico-striatal projection neurons
Vendrell-Llopis, N., Read, J., Boggiano, S., Hetzler, B., Peitsinis, Z., Stanley, C., Visel, M., Trauner, D., Donthamsetti, P., Carmena, J. Lammel, S. and Isacoff, E.Y. (2025). Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns. Neuron 113(5):785-794.e9. doi: 10.1016/j.neuron.2024.12.013.
Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood. Using our cell-specific D1R photo-agonist, we find that D1R activation in D1-expressing neurons in the dorsomedial striatum is sufficient to reinforce preceding neural firing patterns in defined ensembles of layer 5 cortico-striatal neurons of the motor cortex. Strikingly, the reinforcement is independent of a behavioral outcome or a reward, providing insight into the fundamental mechanisms that support cognitive functions like learning, memory, and decision-making.