Figure 8.

Chemogenetic activation of Cajal–Retzius cells in the adult hippocampus. A, Schematic of the experimental procedures. B, In 7-week-old mice neonatally injected with AAV8/hSyn-DIO-hM3D-mCherry, treatment of CNO results in activation of TRP73⁺ CR cells that express the chemogenetic receptor hM3D-mCherry, indicated by c-Fos immunoreactivity (yellow arrows). A CR cell with hM3D-mCherry expression but is not activated (mCherry⁺, c-Fos^–) is indicated by the yellow arrowhead. A CR cell that does not express the hM3D receptor and is not positive for c-Fos is indicated by the white arrowhead. Scale bars, 20 μm. C, Quantification of the percentage of different populations of c-Fos⁺ CR cells of mCherry⁺ or total CR cells. In each of the saline-injected control mice, 69–91 total CR cells were analyzed along the hippocampal fissure and 37–43 total CR cells were analyzed in the lower molecular layer. In each of the CNO-injected mice, 74–91 total CR cells were analyzed along the hippocampal fissure and 39–46 total CR cells were analyzed in the lower molecular layer. Data are presented as scatter plots with all data points shown and error bars representing ±SD. Each data point is an individual animal, whereby three sections were measured for each animal. Statistical analyses were performed using nested t test or nested one-way ANOVA with Tukey’s post hoc test. ****p < 0.0001. The data that demonstrate the absence of CR cell activation in the wild-type mice are shown in Extended Data Figure 8-1.