(a) Fluorescent image showing expression pattern of ChR2-EYFP vector in nucleus accumbens (NAc) core and projections to the ventral pallidum of Adora2a-Cre+/− mice overlayed with brain atlas outline. DS, dorsal striatum; LV, lateral ventricle; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata. Scale bar = 1 mm. (b) Representative traces of action potentials recorded from ChR2-expressing D2-MSNs in NAc core evoked by 0.5 ms-long laser stimulation (33 pulses at 16.6 Hz) before (black) and after TTX (0.5 μM) application (red). Inset, expanded traces showing ChR2-evoked action potentials before (black) and after TTX (red). Scale bar: 50 ms; 20 mV. (c, d) Representative traces of IPSCs evoked by laser stimulation recorded from (c) a ChR2 negative neurons (putative D1-MSN) in NAc core and (d) a neuron in the ventral pallidum region before (black) and after gabazine (gray). (e) Raster plot showing representative example of responding during four consecutive self-administration sessions with laser stimulation OFF and ON (5 min at 16 Hz every 10 min) for a mouse trained on a FR2 schedule. (f) Left, Rewards earned (mean ± SEM) by eight individual Adora2a-Cre+/− mice expressing ChR2 in the D2-MSNs and trained on a FR1, FR2 or FR3 schedule during interspersed cocaine self-administration sessions with laser OFF (black) or ON (blue). Right, Earned rewards during laser stimulation sessions normalized to the rewards earned during laser OFF sessions for every individual mouse. *p < 0.05, one sample t-test. Data are mean ± SEM