Figure 1. SCN-projecting ipRGCs drive light-induced cognitive deficits.

(A) Schemes showing ipRGC projections in Opn4^Cre/+ (control) and Opn4^cre/+ ;Brn3b^zDTA mice. (B-C) Retinal projections (Bm3b(−) ipRGCs) were retained in the SCN, but absent in most ipRGC targets in Opn4^Cre/+ ;Brn3b^zDTA mice. (D-E) The pattern of locomotor activity and circadian periods length under the T7 cycle were similar between groups. Data are mean±SEM, by Student’s t test. n=15. (F) A significant reduction in the time exploring the novel object was observed in mice exposed to the T7 cycle vs. T24-housed mice. The statistical analysis compared to 50% (dotted lines) was: Opn4^Cre/+: T24 p<0.01; T7 p=0.716; Opn4p^Cre/+ ;Brn3b^DTA: T24 p<0.001; T7 p=0.754; by one sample t-test. n=15–35. (G-H) Using the MWM, we found significant deficits during learning (G) and test (H) trials in mice exposed to the T7 cycle, vs. T24-housed mice. n=12–14. (I) T7-housed Opn4^Cre/+ ;Brn3b^DTA mice showed significant LTP deficits, vs. T24-housed mice (n=8–10 mice). Data are mean±SEM. *p<0.05, **p<0.01, by Tukey’s test. 3v: third ventricle; ox: optic chiasm; LGN: lateral geniculate nucleus; Hb: habenular complex; PT: pretectum. Scale bars: 100μm (B), 1mm (C). See also Figure S1.