Extended Data Fig. 10. Optogenetically stimulating VTA dopamine cell bodies during cue pre-exposure enhances subsequent associative learning for that stimulus.

(a) Representative histology showing ChR2 expression in the VTA dopamine cells in the TH-Cre rats. Histology maps showing ChR2 and eYFP expression and fiber placements in the VTA. (b) These experiments were designed to look at the effects of dopamine stimulations during the pre-exposure period when the cues are novel and have not yet acquired value. Ventral tegmental area (VTA) dopamine neurons were stimulated using a blue laser at the time of the cue presentation during pre-exposure sessions. (c) Rats received 2 sessions of stimulus pre-exposure followed by a single session of appetitive conditioning without any stimulation. In the pre-exposure session, the auditory cue was presented in the absence of an outcome whereas in the conditioning sessions, both the pre-exposed and non-pre-exposed cues were followed by the delivery of a food pellet. (d) Averaged responses (Appetitive response = CS response − preCS response) for the eYFP group throughout the 6 conditioning trials (Repeated Measures session × group interaction ANOVA F_(5,80)=0.78 p = 0.56). (e) The difference between the first trial responses to the pre-exposed and non-pre-exposed cues trended towards significance in the eYFP group (paired t-test, t₈=2.13, p =0.06, n=9 rats). (f) There was no difference between pre-exposed versus non-pre-exposed cue responses during the last 3 trials of the conditioning session in the eYFP group (paired t-test, t₈=0.25, p =0.80, n=9 rats). (g) Averaged responses for the ChR2 group throughout the 6 conditioning trials (Repeated Measures session × group interaction ANOVA F_(5,70)=2.42, p = 0.04). (h) The difference between the first trial responses to the pre-exposed and non-pre-exposed cues did not differ in the ChR2 group (paired t-test, t₇=1.11, p =0.30, n=8 rats). (i) The pre-exposed cue responses were significantly higher compared to the non-pre-exposed cue responses during the last 3 trials of the conditioning session in the ChR2 group (paired t-test, t₇=0.008, p =0.02, n=8 rats). This demonstrates that stimulation of the VTA dopamine cell body response to stimuli during pre-exposure enhances the learning of cue-reward associations in the subsequent appetitive conditioning training. Data represented as mean ± S.E.M., # p=0.056, ** p<0.01, ns = not significant.