Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns

Nuria Vendrell-Llopis; Jonathan Read; Samantha Boggiano; Belinda Hetzler; Zisis Peitsinis; Cherise Stanley; Meike Visel; Dirk Trauner; Prashant Donthamsetti; Jose Carmena; Stephan Lammel; Ehud Y Isacoff

doi:10.1016/j.neuron.2024.12.013

Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns

Neuron. 2025 Jan 12:S0896-6273(24)00912-7. doi: 10.1016/j.neuron.2024.12.013. Online ahead of print.

Authors

Affiliations

¹ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Electrical and Computer Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USA. Electronic address: [email protected].
² Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA.
⁴ Department of Chemistry, New York University, New York, NY 10003, USA.
⁵ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
⁶ Department of Chemistry, New York University, New York, NY 10003, USA; Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁸ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Neuroscience, University of California, Berkeley, Berkeley, CA 94720, USA; Weill Neurohub, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated BioImaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: [email protected].

PMID: 39814009
DOI: 10.1016/j.neuron.2024.12.013

Abstract

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 mouse motor cortex. The reinforcement is cumulative and time dependent, with an optimal effect when D1R activation follows the selected neural pattern after a short interval. Our results show that D1R activation in striatal neurons can selectively reinforce cortical activity patterns, independent of a behavioral outcome or a reward, crucially contributing to the fundamental mechanisms that support cognitive functions like learning, memory, and decision-making.

Keywords: D1R; cortico-striatal-thalamocortical loop; dopamine; learning; motor cortex; neuroprosthetic learning; reinforcement; striatum.