Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load
Fig 4
Optogenetic activation of D1R-neurons selectively impaired WM maintenance and retrieval under higher cognitive loads.
A Top: Schematic of virus injection and optic fiber implantation in DMS of Drd1-Cre (+) mice. Bottom: Representative images of ChR2 expression (red) in DMS, with DAPI staining (blue) and projections in SNR. B Photo-stimulation of ChR2 induced c-Fos increase in DMS (green). Scale bar, 100 μm. C Quantitative analysis showed significant c-Fos increase due to photoactivation of DMS D1R-neurons, which was mostly merged with the virus (Independent Samples T test, **p < 0.01, ***p < 0.001). D Schematic of the experimental design for light stimulation during the “delay” phase. E During the 10 s “delay” phase, photoactivation of DMS D1R-neurons didn’t significantly affect WM performance under low cognitive load (RM two-way ANOVA, ns p > 0.05; n = 10 for both groups). F As cognitive loads increased, photoactivation of DMS D1R-neurons during the “delay” phase significantly impaired WM performance (RM two-way ANOVA, ### p < 0.001; Bonferroni’s post-hoc comparisons, delay 30 s, *p < 0.05, delay 60 s, ****p < 0.0001). G Without stimulation, there were no significant differences in WM performance (Independent Samples T test, ns p > 0.05). H Top: Schematic of optic fiber implantation in DMS of Drd1a-Cre/Ai32 mice. Bottom: Representative images of ChR2 expression (green) in DMS, with DAPI staining (blue) and projections into GPi and SNR. I Photo-stimulation of ChR2 induced c-Fos expression in DMS (red). Scale bar, 100 μm. J Quantitative analysis revealed a significant increase in c-Fos expression due to photoactivation of DMS D1R-neurons (Independent Samples T test, *p < 0.05). K Schematic of the experimental design for light stimulation during the “sample”, “delay” or “choice” phase. L No light was delivered during the task acquisition stage (Day 1-6). M Under the 10 s delay condition (low cognitive load), mild photoactivation (~1 mW) of DMS D1R-neurons during the “sample”, “delay” or “choice” phases did not significantly impact WM performance. N Under the 60 s delay condition (high cognitive load), mild photoactivation during the “delay” and “choice” phases markedly impaired WM performance, whereas activation during the “sample” phase had no effect (Independent Samples t test, “Delay light”: *p < 0.05, “Choice light”: **p < 0.01; ChR2 (−) = 9, ChR2 (+) = 8). The data underlying panels C, G, J, M, and N can be found in S1 Data. Data are represented as mean ± SEM.