Fig. 4. Acute deletion of RyR2 in the adult brain leads to compensatory cellular hyperexcitability and dendritic sparsification.

a–f Intrinsic cell firing properties in acute brain sections obtained from Ryr2^fl/fl mice stereotaxically injected with AAV.Camk2α.GFP (control, WT) or with rAAV.Camk2α.GFP-cre (RyR2 knockout, KO) in the hippocampus. a Representative examples of firing properties in control (WT) and RyR2 knockout (KO) CA1 pyramidal neurons. Electrophysiological assessment of (b) input resistance, (c) firing frequency, (d) sag ratio, (e) resting membrane potential and (f) half-width in control (WT) and Ryr2 knockout (KO) neurons (WT: n = 33 cells/11 mice, KO: n = 34 cells/10 mice). g In vivo Ca²⁺ imaging of control C57BL/J6 and Ryr2^fl/fl mice stereotactically injected with both rAAV9.CamK2α-cre and rAAV1.Syn.Flex.GCaMP6m. h Recording of Ca²⁺ signals in CA1 neurons of control (WT) and RyR2 knockout (KO) mice at rest. Upper panel: Overlay of 20 exemplary ΔF/F-traces (black) and denoised traces (red) events. Lower panel: deconvoluted spikes. i Average frequency of Ca²⁺ events in CA1 neurons in control (WT) and RyR2 knockout (KO) mice (WT: n = 5, KO: n = 6). j Frequency distribution of all recorded cells (WT: n = 723. KO: n = 2706). k Three exemplary heatmaps of identified spatially tuned cells for control (WT) and RyR2 knockout (KO) mice trained on a linear treadmill with tactile cues. l Comparison of proportion of identified place cells in control (WT) and RyR2 knockout (KO) mice (WT: n = 4, KO: n = 5). m Comparison of the probability of a significant Ca²⁺ event when mouse passes through place field for control (WT) and RyR2 knockout (KO) mice (WT: n = 4, KO: n = 5). Data are reported as median [25th and 75th percentile]. Student t test or Mann–Whitney test. ***p < 0.001, **p < 0.01, *p < 0.05.