The Cellular and Synaptic Actions of Dopamine During Behavior

Dopamine signaling in the striatum is essential for a wide range of functions, from reward learning to motor vigor and behavioral flexibility. Although dopamine signals fluctuate on sub-second timescales, how these signals are translated into lasting changes in striatal circuit function remains unknown. Resolving this requires cell-type-specific measurements of synaptic and intrinsic properties during behavior, a longstanding technical challenge. Here, we combined in vivo whole-cell membrane potential recordings, simultaneous monitoring and bidirectional manipulation of dopamine signaling in awake, behaving mice to examine how dopamine shapes corticostriatal circuits. Acute manipulations of dopamine over seconds to minutes produced only modest effects on corticostriatal synaptic transmission and no detectable changes in membrane potential dynamics or intrinsic excitability. By contrast, associative learning robustly strengthened identified corticostriatal synapses onto both D1- and D2-expressing spiny projection neurons, yet only D1-SPN plasticity required dopamine signaling. These findings challenge models in which dopamine acts rapidly to tune striatal excitability and identify learning related plasticity as its principal mechanism for shaping striatal circuits in vivo.