Figure 3

Differences in Fos immunoreactivity patterns in Thy1-ChR2 mice subjected to optogenetic stimulation in the hippocampus implies importance of contralateral DG. (a,b) Composite images of Fos immunoreactivity in horizontal sections of the hippocampus ipsilateral (a) and contralateral (b) to optogenetic stimulation from a mouse with progressive AD development. (c) Magnified areas from (a) of CA1, CA3 & DG, respectively. (d) Magnified area of DG from (b), indicating cell body localization of Fos by nuclear stain (Hoechst, blue). (e–g) Three general patterns of Fos immunoreactivity in the DGC (dashed outlines): (e) bilateral (BiL); (f) ipsilateral to optogenetic stimulation (IpL), (g) absence of Fos immunoreactivity bilaterally (non-activated, NA) (e & g are from the same animals as recordings in Fig. 1a & b, respectively). (h) Illustration of areas selected for quantification of Fos immunoreactivity. DGC marked in magenta. DM: dorsomedial, DL: dorsolateral, M: middle, V: ventral. (i) Ipsilateral and (j) contralateral mean Fos intensity in the BiL (n = 4), IpL (n = 10) and NA (n = 7) subsets (NA as control, Kruskal-Wallis test with Dunn’s post-test). Note that the BiL group completely matches the Progr AD group (Figs 1 & 2). (k) Control group (n = 3) exposed to trains of orange (593 nm) light. (l) Relative magnitude (ratio) of contra- to ipsilateral Fos intensity, comparing BiL and IpL (unpaired t-tests). Scale bars in a,b: 200 µm, c,d: 40 µm, e–g: 50 µm. Error bars: ±SD. *P < 0.05, **P < 0.01, ****P < 0.0001, ns: non-significant, see Table 1 and Results for exact P-values.