Motor Cortex Layer V Pyramidal Neurons Exhibit Dendritic Regression, Spine Loss, and Increased Synaptic Excitation in the Presymptomatic hSOD1^G93A Mouse Model of Amyotrophic Lateral Sclerosis

Apical dendritic regression, spine loss, and increased EPSC frequency occurs in motor cortex LVPNs of presymptomatic SOD1 mice. A, B, Dendritic arbors of NB-filled LVPNs within primary motor cortex from WT (A) and SOD1 (B) mice. C–F, LVPNs show decreased apical dendritic spines in P23 and P31 SOD1 mice compared with age-matched and litter-matched WT mice. G–J, Scatterplots of morphological measurements in P21–P27 and P28–P40 SOD1 and WT LVPNs, showing decreased total dendritic arbor length in P28–P40 SOD1 LVPNs (G), decreased apical dendritic arbor length in P28–P40 SOD1 LVPNs (H), and decreased dendritic spine densities per 100 μm apical and basal dendrite respectively in both P21–P27 and P28–P40 SOD1 LVPNs (I, J). K, Representative electrophysiology traces showing increased EPSC frequency at −70 mV holding voltage in SOD1 LVPN at ages P24 and P38. L, Scatterplot showing increased EPSC frequency in both P21–P27 and P28–P40 SOD1 LVPNs compared with WT. Two-way ANOVA with Bonferroni's post-test; *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. For morphology: WT, n = 6 (P21–P27) and n = 14 (P28–P40); SOD1, n = 9 (P21–P27) and n = 15 (P28–P40); For EPSCs: WT, n = 6 (P21–P27) and n = 13 (P28–P40); SOD1, n = 5 (P21–P27) and n = 19 (P28–P40). Scale bars: A, B, 250 μm; C–F, 5 μm.