Figure 4. Dopamine release in the nucleus accumbens core does not follow prediction error patterns during unexpected addition and omission of stimuli.
A series of experiments were run to test how unexpected addition and omission of predicted and unpredicted stimuli influence dopamine release patterns. Mice first were trained with Pavlovian fear conditioning. (A) Footshocks were unexpectedly omitted in 20% of trials. Freezing during each trial type was not different (paired t-test, t5=1.47, p=0.20; n=6). (B-C) Dopamine responses at the time of the omitted footshocks were larger than the critical z-score at p=0.05 level, indicating a significant dopamine event even though the shock itself was not presented (independent t-test; t29=3.92, p=0.0005). Dopamine responses at the time of the predicted footshock were lower in amplitude than when the footshock was present (Nested ANOVA, F(1,156)=7.39 p=0.0073). (D-E) Dopamine responses to the footshocks during the omission session (when shock probability was 80%) were larger than the shock response during the initial fear conditioning session (when shock probability was 100%) (Nested ANOVA, F(1,222)=21.48, p<0.0001). (F) Freezing during acquisition and extinction (Fear conditioning vs. Extinction 2, paired t-test, t5=3.31, p=0.021; n=6). (G-H) Dopamine response to the cue did not change over extinction, although it returned to baseline (Nested ANOVA, F(2,331)=3.37, p=0.035; Early extinction vs. Late extinction, p=0.009). (I-J) Dopamine responses to the shock delivery period decreased over extinction. Responses to omitted shocks during extinction were smaller than when footshocks were present. (Nested ANOVA, F2,329=9.76, p=0.0001; Fear conditioning vs. Extinction Day 1 p=0.0005; Fear conditioning vs. Extinction Day 2 p<0.0001). (K) A novel, neutral light was presented in 20% of trials. Freezing to the tone and tone + light trials show that the novel cue reduced freezing (unpaired t-test, t5=4.23, p=0.008; n=6) and (L-M) dopamine responses to the tone + novel cue was increased (Nested ANOVA, F1,156=6.44, p=0.012). (N-O) Dopamine response to the footshocks did not differ between trials (Nested ANOVA, F1,156=0.35, p=0.557). Data represented as mean ± S.E.M. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.