Fig. 4.

Optical stimulation of hippocampal efferents suppresses the stress-induced CORT response.

a) ChR and EYFP were expressed in the CA1 region of male C57/Bl6 mice bilaterally and optical fibers targeted hippocampal terminals in the fornix anterior to the BNST. Each animal was randomly assigned to 20Hz stimulation at 10 mW or mock stimulation at 0.1 mW and the opposite treatment 1 week later. Animals were restrained for 15 min and received 20Hz optical stimulation 2 s on, 2 s off for the duration of the restraint. Blood was sampled via tail snip at 0, 15, 30, 60, and 120 min timepoints for CORT assay. b) Comparison of the timecourse of CORT responses in the full power and mock 20Hz stimulation trials. Mixed-effects ANOVA was performed on the resulting curve, with time effect (n = 6, F_2.121,20.15 = 31.10, p < 0.0001) and treatment effects (n = 6, F_1,10 = 5.186, p = 0.0460). c,d) Comparison of the area under the curve and peak CORT responses in the paired trials from b showing significant effects of hippocampal stimulation. Paired t-tests for mock vs stim AUC (n = 5, p = 0.0184) and peak value (n = 5, p = 0.0105) were significant. *, p < 0.05; **, p < 0.01. e,f,g) The same data after resorting by recording order demonstrating no significant effects. When segregated by order of recording, mixed effects ANOVA maintains time effect (n = 6, F_2.397,22.77 = 34.24, p < 0.0001) but loses treatment effect (n = 6, F_1,10 = 0.4163, p = 0.5333). Similarly, paired t-tests performed on recording order AUC (n = 5, p = 0.2936) and peak CORT (n = 5, p = 0.5404) were not significantly different.