Figure 1.

Unique Morphology of the Human NMJ

(A) Representative confocal micrographs from 4 lower limb muscles. Human NMJs are smaller, with a thinner axon, less complex nerve terminals and a distinctive “nummular” endplate. Scale bar, 10 μm.

(B) Bar charts demonstrating significant species-specific differences across a range of pre- and post-synaptic variables. Each bar represents the mean (±SEM) of >600 human NMJs (and 240 mouse NMJs). Unpaired t test and Mann-Whitney test.

(C) Scatterplots showing correlation between nerve terminal area and axon/muscle fiber diameter. Each data point is an individual muscle (mean of 40 NMJs) (72 human and 24 mouse muscles). NMJ morphology was more closely correlated with structural features of the pre-synaptic cell (motor axon) in both species. Pearson correlation.

(D) Left/right muscles pairs from the same human case were compared with 3 mouse controls. Each data point (in the pair) is an individual muscle (left or right); the intervening line is the mean of the 2 sides. Laterality did not influence NMJ morphology in either species.

(E). Effect of co-morbidities on human NMJ morphology. No significant morphological differences could be attributed to either diabetes mellitus (DM) or peripheral vascular disease (PVD). Unpaired t tests.

^∗∗∗∗p < 0.0001, ^∗∗∗p < 0.001, ^∗∗p < 0.01, ^∗p < 0.05.