Fig. 10: CalEx disrupts the astrocytic feedback loop and formation of spatial memory.

a C57Bl6/N mice were injected bilaterally (CA1, hippocampus), with either AAV.gfaABC1D-tdTomato (sham) or AAV.gfaABC1D-mCherry-hPMCA2w/n (CalEx)39. Absence of overlap between mCherry expression and neuronal cell layers (lower panel, scale bar 500 µm, see Supplementary Fig. 9). b In sham-injected mice, 10 Hz stimulation decreased the dendritic spike threshold stimulus significantly (left panel; gray: 0.31 ± 0.03 µA vs. 0.26 ± 0.03 µA, n = 6, p = 0.0021, two-sided paired Student’s t test) but not in CalEx mice (red: 0.30 ± 0.05 µA vs. 0.30 ± 0.05 µA, n = 5, p = 1.00, two-sided paired Student’s t test). The change was significantly larger in sham mice (right panel; sham vs. CalEx, −16.47 ± 2.61 vs. 0.10 ± 2.19, n = 6 and 5, p = 0.0011, two-sided Student’s t test). c Corresponding results for the slow component (left panel; sham, gray: 13.36 ± 2.06 mV vs. 15.47 ± 2.42 mV, n = 6, p = 0.016, two-sided paired Student’s t test; CalEx, red: 13.66 ± 1.11 mV vs. 13.18 ± 0.79 mV, n = 5, p = 0.23, two-sided paired Student’s t test). Right panel: relative change 10 Hz/baseline (sham vs. CalEx, 15.09 ± 4.29 vs. −2.80 ± 2.36, n = 6 and 5, p = 0.0073, two-sided Student’s t test). d Testing arena for object location memory (also Fig. 8). e Similar total exploration time during acquisition between groups (sham vs. CalEx: 3.76 ± 0.80 s vs. 4.19 ± 0.74 s, n = 7 and 5, p = 0.71, two-sided Student’s t test). f Sham mice explored the object in the novel location significantly more compared to, CalEx mice (0.35 ± 0.11 vs. −0.18 ± 0.17, n = 7 and 5, p = 0.019, two-sided Student’s t test). 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. Source data are provided as a Source Data file.