Fig. 7: Modulation of the circadian clockwork alters AMPA receptors synaptic expression and homeostatic plasticity in mPFC.

a, b Representative western blots and quantitative data of synaptic AMPA receptors subunits GluA1 and GluA2 levels normalized to Homer1b/c and PSD95 in mPFC of WT mice 24 h after SR10067 application (a), and 6 h and 24 h post SR1078 injection (b). (n = 5, a: two-tailed Student’s t test: *P = 0.0422 for GluA1, **P = 0.0069 for GluA2, b: one-way ANOVA with Bonferroni post hoc test: *P < 0.05, ***P < 0.001). c Experimental design: WT mice were subjected to the CDM protocol before undergoing implantation of ECoG, LFP and EMG recording electrodes. After recovery, mice were recorded in their home cage over 32 h from ZT0, with treatment (vehicle/ketamine/SR1078) administered at ZT06. d, e Delta power (0.5–4 Hz) of LFP signal recorded from the mPFC (d) and ECoG signal (e) recorded during slow wave sleep (SWS) across 12 h:12 h LD conditions (n = 14 mice CDM/vehicle; n = 6 SR1078; n = 4 KET; repeated measures mixed-effects model two-way ANOVA with Bonferroni post hoc test *P < 0.05, **P < 0.01 vs CDM/vehicle). Black arrow indicates time of treatment administration. f Schema summarizing the effects of RORα/γ activation on BMAL1, Homer1a and synaptic AMPAR expression in the mPFC and the relation to depression-like behavior. Data are presented as mean ± SEM and the individual data points are depicted. See also Supplementary Fig. 7 and Supplementary Data 1. Source data are provided as a Source Data file.