Fig. 1

Effects of sterile gray matter encephalitis, induced by pyramidal neuronal ablation, on diverse behavioral paradigms. a Schematic description of the diphtheria toxin chain A (DTA) allele. Tamoxifen-dependent Cre-mediated excision of a STOP-cassette leads to expression of DTA, subsequent inhibition of protein synthesis, and cell death. b Genotype of the DTA model targeting pyramidal neurons and tamoxifen dosing scheme. Cohorts induced with 3 × tamoxifen included 16 DTA and 18 control mice. The 5 × tamoxifen cohort comprised 16 DTA and 19 control animals. c Fluorojade staining of hippocampal sections at 1 week after 5 × tamoxifen induction. Note the massive acute neurodegeneration and pyramidal neuronal loss. d Experimental outline illustrates groups, experiments and timeline of testing (DPI = days post induction, CRW = complex running wheel, MRI = magnetic resonance imaging). e Cognitive testing in Morris water maze (MWM), with hidden platform task showing significantly inferior learning curve (latency to reach the platform) of 3 × DTA mice (light red) compared to control (black); repeated measures mixed-model ANOVA; mean ± SEM. f Spatial memory testing in the probe trial indicating significantly less time spent in target quadrant (TQ, formerly containing hidden platform), less visits to TQ and longer latency to reach TQ of 3 × DTA mice. Total swimming distance of both groups did not differ. Data presented as mean ± SD. g Testing 5 × tamoxifen groups for anxiety and exploratory behavior in the open field showed a tendency of increased escape latency from center towards periphery. DTA compared to control mice covered less distance, spent less time in the periphery and more time in “mid” (intermediate zone between center and periphery). Time in center showed no differences between both groups (p = 0.9546). Data presented as mean ± SD. h 5 × DTA compared to control mice displayed a decreased prepulse inhibition; repeated measures mixed-model ANOVA; mean ± SEM