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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

From: Loss of glucocorticoid receptor phosphorylation contributes to cognitive and neurocentric damages of the amyloid-β pathway

Fig. 5

Lack of p-GR decreases synaptic plasticity and the mobilization of AMPA receptors in task-induced dendritic spines. a Experimental timeline in Nr3c1+/+-thy1-YFP and Nr3c1ki/ki-thy1-YFP double transgenic mice and timelapse imaging in motor cortex. b Interaction of training and genotype on spine formation and elimination. Means ± SEM of N(+/+, ki/ki) = 4,4 mice without and 6,5 with training. Three-way ANOVA: effect of genotype on formation F1,59 = 55, P < 0.0001; effect of time post-CORT injection on formation F3,59 = 422, P < 0.0001; effect of training on formation F1,59 = 2.7, P = 0.1; effect of genotype on elimination F1,61 = 17.9, P < 0.0001; effect of time post-CORT injection on elimination F3,61 = 129, P < 0.0001; effect of training on elimination F1,61 = 5.8, P = 0.01 post-hoc Tukey test comparing genotypes *P = 0.01, **P = 0.007, ***P < 0.0001 or training groups #P < 0.02, ###P < 0.0001. c Field potentials (Means ± SEM) recorded in acute slices of motor cortex on the next day of rotarod training. High-frequency stimulation (HFS) and low–frequency stimulation (LFS) with half the intensity to reach a maximal response in parallel fibers placed ≈500 μm away from the recording electrodes induced LTP and LTD, respectively. Quartiles and median of dataset from Min-to-Max (N(+/+,ki/ki) = 5,6 HFS; 8,5 LFS mice without training and 5,6 HFS; 9,6 LFS with training). Mann–Whitney test comparing genotypes *P < 0.01. d Protocol of metaplasticity with 3 consecutive HFS or LFS interspaced with at least 20-min intervals to return to baseline activity. Quartiles and median of dataset from Min-to-Max (N(+/+,ki/ki) = 5,5 HFS; 3,3 LFS mice without training and 8,6 HFS; 8,6 LFS with training). Mann–Whitney test comparing genotypes *P = 0.029, **P = 0.008. e Two-photon uncaging of AMPA at newly formed dendritic spines on the next day of rotarod training. Spine head enlargement normalized to the size prior AMPA uncaging (blue arrow). Means ± SEM of N(+/+, ki/ki) = 13,15 spines without and 18,33 with uncaging. Three-way ANOVA: effect of genotype F1,340 = 4 P = 0.04; effect of uncaging F1,340 = 23.7 P < 0.0001 post-hoc Tukey comparing genotype and uncaging.#P = 0.02

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