Dominant-negative NR4A1 counteracted the effects of chronic stress.
A. Two-photon images of dendritic Mito-dsRed and GFP in pyramidal neurons electroporated with dox-dependent ΔAF1 in cortex of mice subjected to 14 days of stress.
B. Topography of mitochondria and spine remodeling in dendritic territories imaged twice 14 days apart ± dox.
C. Clustered spine dynamics on stress OFF dox is greater than chance. Histogram shows the distribution of spine permutations in 30,000 simulations of randomized new spine positions (mean Gaussian fit = 0.58 ± 0.51, observed = 0.76 ± 0.1, N = 5 OFF, p = 0.007 and mean Gaussian fit = 0.77 ± 0.03, observed = 0.84 ± 0.09, N = 6 ON, p = 0.056).
D. Cross-clustering of spine dynamics and mito remodeling on stress OFF dox is greater than chance. Histogram shows the distribution of spine permutations in 30,000 simulations of randomized new spine positions with respect to mito remodeling (mean Gaussian fit = 3.5 ± 0.14, observed = 0.85 ± 0.07, N = 5 OFF, p < 0.0001 and mean Gaussian fit = 1.6 ± 0.1, observed = 0.71 ± 0.09, N = 6 ON, p < 0.0001).
E. Gain/loss of dendritic spines in clusters ≤5 μm. Two-way ANOVA: dox x clustered dynamics F1,18 = 52.21, p < 0.0001 post-hoc Tukey test: OFF vs ON dox groups *p < 0.0001, N = 5 OFF, 6 ON mice.
F. Gain/loss of mitochondrial dendritic coverage. Two-way ANOVA: dox x mitochondrial remodeling F1,18 = 47.59, p < 0.0001 post-hoc Tukey test: OFF vs ON dox groups *p < 0.0001, N = 5 OFF, 6 ON mice.
G. Effect of dox on the net change of mitochondrial coverage and spine density induced by chronic stress. Student two-tailed T-test comparing OFF and ON dox groups *p < 0.0001, N = 5 OFF and 6 ON dox mice.
H. Correlation (Pearson) between mitochondria and spine changes in dendritic territories of N = 5 OFF, 6 ON mice.