Fig. 6: Inactivation of ACh release in the anterior dorsal striatum impairs behavioral changes during extinction.
a Schematic showing the bilateral injection strategy for the selective expression of TelC in CINs in aDS. b Top: Fluorescence image in a coronal section of the striatum showing bilateral TelC expression in aDS for a representative mouse. Bottom: Magnification of the boxed area in top image showing selective expression of TelC in CINs. Experiments were independently repeated n = 6 times with similar results. c Left: Schematic showing the strategy for verifying effects of TelC mediated suppression of CINs on ACh release to unpredicted rewards. Right: Mean ∆F/F across all trials (n = 209) aligned to unpredicted reward delivery with quasi-simultaneous 405 nm (gray) and 470 nm (green) illumination in two mice expressing the ACh3.0 sensor and TeLC in CINs. Shaded regions, S.E.M. d Mean (± S.E.M.) % time spent licking during the 3 s of cue presentation (both light and tone cues merged) for pre learning, post learning and extinction (20% reward probability cue only) for both TelC and control mice. Each dot is an individual mouse (n = 8 for control and n = 6 for TelC mice). *p < 0.05, ***p < 0.001, two-tailed repeated measures two-way ANOVA followed by Tukey post hoc analysis for comparisons within and between TelC and control mice. e same as (c) for % time licking during ITI periods, data are presented as mean (± S.E.M). The exact p-values and additional statistical details can be found in Supplementary Table 1. f Box plots showing the ratio of mean cue period licking during partial extinction (20% reward probability, light and tone combined) relative to post learning (100% reward probability), indicating no change in cue licking in TelC mice and a reduction in normalized cue licking in control mice during partial extinction. Each dot represents an individual mouse (n = 8 for control and n = 6 for TelC mice). Box plots with whiskers extending from the minimum to the maximum values. The center line represents the median, the box bounds show the 25th and 75th percentiles, and the + symbol indicates the mean. Mann-Whitney U test, U(8.6) = 7, *p = 0.0293 (two-tailed). Brain schematics in (a) and (c) were adapted from the Allen Mouse Brain Common Coordinate Framework (CCFv3) (https://atlas.brain-map.org/). Source data are provided as a Source data file.
