Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load
Fig 3
Optogenetic inhibition of D1R-neurons selectively improved WM maintenance and retrieval under higher cognitive loads.
A Top: Schematic illustrating virus injection and optic fiber implantation in DMS of Drd1-Cre (+) mice. Bottom: Representative images showing ArchT expression (green), DAPI staining (blue) in DMS, and its projections to the GPi and SNR. B Photoinhibition of ArchT resulted in c-Fos induction in DMS (red). Scale bar, 100 μm. C Quantitative analysis demonstrated a significant increase in c-Fos expression due to photoinhibition of D1R-neurons, primarily in cells not co-localized with the virus (Independent Samples t test, **p < 0.01). D Schematic of the experimental design for light stimulation during the “sample” phase. Photoinhibition of DMS D1R-neurons during the “sample” phase did not significantly affect WM under both low (E) and high cognitive loads (F, RM two-way ANOVA, ns P > 0.05; GFP = 10, ArchT = 11). G Schematic of the experimental design for light stimulation during the “delay” phase. Photoinhibition of DMS D1R-neurons during the 10 s “delay” phase did not significantly impact WM performance under low cognitive load (H, RM two-way ANOVA, ns p > 0.05; GFP = 12, ArchT = 13), but significantly improved WM performance under high cognitive load (I, RM two-way ANOVA, main effect, F1, 30 = 14.95, ###p < 0.001; interaction, F3, 69 = 3.690, p < 0.05; Bonferroni’s post-hoc comparisons, Delay 60s, ****p < 0.0001). J Schematic of the experimental design for light stimulation during the “choice” phase. Photoinhibition of DMS D1R-neurons during the “choice” phase did not significantly impact WM performance under low cognitive load (K, RM two-way ANOVA, ns p > 0.05; n = 9 for both groups), but significantly improved WM performance under high cognitive load (L, RM two-way ANOVA, main effect, F1, 16 = 9.066, ##p < 0.01; interaction, F3, 48 = 1.536, p > 0.05; Bonferroni’s post-hoc comparisons, Delay 60s, **p < 0.01). The data underlying panel C can be found in S1 Data. Data are represented as mean ± SEM.