Prolonged self-motivated exercise sensitizes NMJ to axotomy-induced degeneration. (A) Representative circadian activity pattern in a WldS mouse. Each horizontal trace is a record of activity over a 24 h period, divided into 12 h of light and 12 h of darkness. Each vertical line is proportional to the number of wheel revolutions. (B) Integrated activity of WldS mice (red) and C57Bl6 mice (blue) (n = 6 mice in each case) shows no discernible difference in the pattern or amount of circadian activity in the two strains of mice. As expected, most activity was in the dark. (C) Box-whisker plots of incidence (median and interquartile range; outliers >90 percentile shown as dots) of unresponsive FDB muscle fibers (neither MEPPs, nor evoked EPPs observable on tibial nerve stimulation in isolated preparations) in four groups of mice: controls with no nerve section; WldS controls with no running wheels, 5 day post-axotomy; WldS mice with provision of running wheels for 2 weeks, then 5 days post axotomy; WldS mice with provision of running wheels for 4 weeks, then 5 days post axotomy. n = 7–11 muscles per group. (D) Plot of incidence of Responsive fibers (evoked EPPs) versus recorded mean diurnal running wheel activity, averaged over 4 weeks and assayed 5 days post axotomy. While there was no clear evidence of regression or correlation, mice running the least distance had stronger levels of synaptic protection than those running the most. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)