Fig. 6: Deletion of astrocytic type 1 CBRs (CB1Rs) disrupts the frequency-dependent modulation of dendritic spiking by pyramidal cell activity.

a Generation of sham and aCB1KO mice. b Sample CA1 pyramidal cell filled with Alexa Fluor 594 (40 µM, blue, whole-cell patch clamp), an iontophoresis pipette (blue) and expression of tdTomato (indicator of astrocytic CB1R deletion, aCB1KO). Left panel: scale bar 20 µm. Right panel: enlarged white box from right panel, scale bar 5 µm. c Dendritic spike threshold decrease during 10 Hz alveus stimulation absent aCB1KO mice but preserved in wildtype (WT) and sham control mice (left panel; WT: 0.48 ± 0.05 µA vs. 0.40 ± 0.04 µA, n = 7, p = 0.0026, two-sided paired Student’s t test; sham: 0.36 ± 0.03 µA vs. 0.31 ± 0.03 µA, n = 8, p = 0.00071, two-sided paired Student’s t test; aCB1RKO: 0.31 ± 0.05 µA vs. 0.31 ± 0.04 µA, n = 9, p = 1.00, two-sided Wilcoxon signed-rank test). Decrease after D-serine application (10 µM) is preserved in aCB1KO mice (0.33 ± 0.03 µA vs. 0.29 ± 0.03 µA, n = 7, p = 0.000096, two-sided paired Student’s t test). Right panel: change (filled circles, left panel) relative to baseline (open circles, left panel). One-way ANOVA with post-hoc Fisher’s LSD. d Corresponding slow component changes during alveus stimulation (WT: 19.18 ± 1.94 mV vs. 22.14 ± 2.19 mV, n = 7, p = 0.031, two-sided paired Student’s t test; sham: 13.83 ± 1.50 mV vs. 16.41 ± 1.29 mV, n = 8, p = 0.0056, two-sided paired Student’s t test; aCB1KO: 13.73 ± 1.36 mV vs. 12.83 ± 1.14 mV, n = 9, p = 0.14, two-sided paired Student’s t test) and D-serine application (aCB1KO: 10.51 ± 1.33 mV vs. 12.70 ± 1.56 mV, n = 7, p = 0.0011, two-sided paired Student’s t test). Right panel: change (filled circles, left panel) relative to baseline (open circles, left panel). One-way ANOVA with post-hoc Fisher’s LSD. Data are expressed as mean ± s.e.m. in the legend and displayed in box plots. The box indicates the 25th and 75th, the whiskers the 5th and 95th percentiles, the horizontal line in the box the median and the mean is represented by a filled circle. Throughout panels *p < 0.05, **p < 0.01, ***p < 0.001. Supplementary Table 2 for further information. Source data are provided as a Source Data file.