Distinct roles for direct and indirect pathway striatal neurons in reinforcement

Abstract

Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1 receptor–expressing neurons induced persistent reinforcement, whereas stimulating D2 receptor–expressing neurons induced transient punishment, indicating that activation of these circuits is sufficient to modify the probability of performing future actions.

Fig. 1. dMSN stimulation induces persistentreinforcement, while iMSN stimulation induces transient punishment

(a, b) percent of contacts with the laser-paired trigger across each session for dMSN-ChR2 (green) and iMSN-ChR2 (red) mice (2-min bins). (c, d) percent of contacts with the laser-paired trigger during retraining and extinction sessions (2-min bins). (e, f) probability of subsequent contact with the laser-paired trigger following a previous trigger activation, for dMSN-ChR2, YFP control, and iMSN-ChR2 mice. (g) peri-event time histogram of velocity for dMSN-ChR2 and iMSN-ChR2 mice following contact with the laser-paired (blue) or inactive (grey) triggers. Time of stimulation for the laser-paired trigger shown in blue. Error bars in all panels represent standard error of the mean.

Fig. 2. Acquisition and expression of trigger preference are not influenced by dopaminergic antagonists

(a) average velocity and total number of trigger contacts for mice treated with saline (black bars) and DA antagonists (grey bars). (b) acquisition of trigger preference for saline- (darker lines) and DA antagonist-treated mice (lighter lines) (days 1–3, 2-min bins) for dMSN- (green) and iMSN-ChR2 (red) mice. (c) quantification of trigger preference for the entire duration of each session. (d) expression of trigger preference in the saline-treated mice from (c) in a subsequent session in which mice were administered DA antagonists (day 4, 2-min bins). Error bars in all panels represent standard error of the mean.

Fig. 3. dMSN and iMSN stimulation modify place preference

(a) percent of time animal spent in laser-paired compartment for dMSN-ChR2 (green) and iMSN-ChR2 (red) mice (2-min bins) for two training days (laser illumination when the animal is in the laser-paired chamber), and for a test day (no laser illumination in either chamber). Quantification of place preference during the first two min of each session (b) and for the entire duration of each session (c), for dMSN-ChR2 and iMSN-ChR2 mice. Error bars in all panels represent standard error of the mean.