Fig. 6: Postnatal fluoxetine treatment recreates the SERT-KO transition from cortical hypoactivity to hyperexcitability.

a Animals were dosed orally with either 10% sucrose (control vehicle) or 10 mg/kg of fluoxetine (SSRI) daily from P2 to P14, injected neonatally with GCaMP6s, implanted with a cranial window and head-fixing plate at P6 and imaged from p7 to P16. Raster plot of neuronal spiking across 10 min baseline from sucrose (b) and SSRI (c) postnatally-treated representative mice during Th-SERT (P8), illustrating the presence of H- and L-events. d Representative peri (±5 s) H-event GCCaMP6s signal heatmaps of 2000 cells in recordings from a single sucrose- (left) and SSRI- (right) treated P8 mouse. Heat map constructed from averaging the signal across all H-events detected on each mouse during a 20 min baseline recording. Violin plot of mean H-event (e) amplitude, (f) frequency and (g) duration in SSRI- versus sucrose-treated mice during Th-SERT (e, t-test p = 0.040, f, Mann–Whitney U-test: p = 0.016, g, Mann–Whitney U-test: p = 0.310). h Cumulative probability of ΔF/F 20 min baseline values of all Sucrose/SSRI treated animals at P7-10 (a, Kolmogorov–Smirnov test: p = 0.022) i, Baseline pairwise cell correlations across distance in SSRI-treated mice compared to sucrose-treated littermate controls at P9 (Two-way ANOVA, treatment p < 0.001). Stimulus-triggered average trace (left) and response amplitude (right) of GCaMP6s signal across all cells and mice during Th-SERT (j t-test p = 0.018) and Adult SERT (k, Mann–Whitney U-test, p = 0.254), in SSRI- or Sucrose-treated mice. Sample sizes are 12 (Control) and 12 (SSRI). Traces, errorbar and cumulative probability plots are presented as mean ± SEM. Violin plots are presented as mean values ± max/min value.