Opponent regulation of striatal output pathways by dopamine and serotonin

2025 · doi:10.1101/2025.04.17.649431
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ABSTRACT Classic theories propose opponent functions for striatal dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT), with DA promoting approach and 5HT promoting patience or avoidance. How these neuromodulators regulate downstream circuits to achieve such antagonistic effects remains mysterious. Here, we mapped striatal 5HT receptor expression and recorded from genetically-identified striatal neurons to demonstrate that DA and 5HT selectively activate distinct populations of striatal neurons to exert opponent control over striatal output. Competing Interest Statement N.E. is a consultant for Boehringer Ingelheim. R.C.M. is on leave from Stanford serving as the Chief Scientific Officer at Bayshore Global Management and is on the scientific advisory boards of MapLight Therapeutics, MindMed, and Aelis Farma.

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