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. Author manuscript; available in PMC: 2023 Aug 1.
Published in final edited form as: Nat Neurosci. 2022 Jul 28;25(8):1071–1081. doi: 10.1038/s41593-022-01126-1

Figure 6. Optogenetically enhancing dopamine responses during pre-exposure prevents blunted dopamine responses to the pre-exposued cue during subsequent learning.

Figure 6.

(a) In mice (n= 12 mice, 4 males, 8 females), AAV5-Syn-FLEX-rc[ChrimsonR-tdT] was co-injected with AAV9.rTH.PI.Cre into the VTA to achieve dopamine-specific expression of excitatory or inhibitory opsins. AAV9.CAG.dLight1.1 was injected in the NAc core. (b) Dopamine terminals were optogenetically photostimulated (via Chrimson) at the time of the neutral cue during pre-exposure in first four sessions. Dopamine was recorded in fear conditioning sessions via dLight1.1 in the same animals. (c) Photostimulation of dopamine terminals during the pre-exposure period disrupted the latent inhibition effect observed in the first fear conditioning session (2-way ANOVA F(1,10)= 11.40, p=0.007; Bonferroni multiple comparisons: Controls pre-exposed vs. non-pre-exposed p=0.012; ChR2 pre-exposed vs. non-pre-exposed p>0.5). (d) Dopamine responses to the CS+ and pre-exposed CS+ in control animals. (e) Peak dopamine response to the CS+ was higher than to the pre-exposed CS+ (Nested ANOVA F(1,65)= 19.02, p=0.00005). (f) Dopamine signal to the CS+ and pre-exposed CS+ in Chrimson+rTH.PI.Cre animals. (g) Peak dopamine response to the CS+ was not different as compared to pre-exposed CS+ (Nested ANOVA F(1,65)= 1.23, p=0.2713). Data represented as mean ± S.E.M., * p < 0.05, ****p < 0.0001, ns = not significant.