Fig. 7: D2-MSNs are essential in the extinction of aversive Pavlovian associations.
A After aversive Pavlovian conditioning, animals were exposed to 9 days of extinction (CS2, no US2). B, C Freezing responses of D1-cre or A2A-cre animals, respectively, showing a decrease in aversive conditioned responses throughout extinction. D Percentage of excitatory and inhibitory responses to CS2 in the day of aversive conditioning and in extinction sessions 1, 5 and 9 for D1-MSNs and D2-MSNs. E Heatmaps of tracked D1-MSNs or G tracked D2-MSNs showing the CS2 responses throughout days. In heatmaps, neurons are aligned to CS2 response on the conditioning day. F AUCs of D1-MSNs or H D2-MSNs CS responses throughout the days. I Scheme of the optogenetic manipulation during aversive Pavlovian conditioning. D1- and A2A-cre mice were exposed to a fear conditioning session without optogenetic manipulation. After, mice were exposed to 9 days of extinction, with optical excitation or optical inhibition of D1- or D2-MSNs during the 10 seconds of CS exposure (excitation: 25 ms light pulses at 20 Hz; 473 nm; nD1-YFP = 19, nD1-ChR2 = 20; nA2A-YFP = 19, nA2A-ChR2 = 17; inhibition: constant light; 589 nm; nD1-YFP = 19 nD1-NpHR = 17; nA2A-YFP = 19, nA2A-NpHR = 18). J Optogenetic excitation or K inhibition of D1-MSNs during extinction sessions does not alter the extinction of conditioned responses. L Optogenetic excitation of D2-MSNs during extinction sessions does not alter conditioned responses. M Optogenetic inhibition of D2-MSNs during CS period in extinction sessions delays the extinction of conditioned responses, as shown by the increased freezing behavior in relation to YFP animals (Two-way ANOVA, Bonferroni post hoc). Data are presented as mean values +/−SEM. **p < 0.01, ***p < 0.001. Source data are provided as a Source Data file. Created in BioRender. Pinto, L. (2024) BioRender.com/p41z755.
