Figure 7.

Effects of chemogenetic activation of the CA1 Egr1-dependent activated neurons during the rotarod task. A, Design of the AAV vector to express hM3D(Gq) only in cells with Cre recombinase activity. B, Egr1-CreER^T2 mutant mice used. C, Scheme depicting the behavioral characterization in the present figure (colored). D, Schematic location of the injection site for each mouse (only left hemisphere is shown). E, Representative image of a transduced hippocampus from a mouse treated with CNO. F, Representative images of CA1 in mice from E. Empty arrowheads designate nontransduced cells, white arrowheads designate transduced cells. G, Quantification of cFos immunofluorescence intensity in the CA1 pyramidal cell layer of transduced mice and treated with 4-HT and Vehicle (n = 8) or CNO (n = 9). Mean ± SEM. Mann–Whitney t test (sum of ranks A, 36; B, 117, U = 0, p < 0.0001). H, Accelerating rotarod task in transduced mice. Arrows indicate treatment with 4-HT and arrowheads treatment with CNO. Data are mean ± SEM. Two-way ANOVA identified significant differences between groups on last day of training (F_(1,76) = 26,41, p < 0.0001). I, Two independent groups of WT mice treated with vehicle (n = 10) or CNO (3 mg/kg, n = 11), respectively, were subjected to the accelerating rotarod task with the same design as in H. J, A new cohort of mutant mice as in B, were subjected to the same experimental design as in A–C but without 4-HT administration to rule out potential leakiness of the system. Data are mean ± SEM, analyzed by two-way ANOVA (no significant differences were detected between groups). K, Postmortem hippocampal examination in mice from J shows no recombination because of the absence of 4-HT administration. Data are mean ± SEM. Scale bars: 300 µm (E), 60 μm (F), and 100 μm (K). DG: dentate gyrus, CA1: cornu amonis 1, CA3: cornu amonis 3, SO: stratum oriens, SP: stratum pyramidale, SR: stratum radiatum.