Figure 7.
Use-dependent impairment of neuromuscular synaptic transmission in UbG76V-GFP-Syb2 mice.
A
,
B
, Sample EPP traces evoked by a 1-s-duration train containing an increasing frequency of stimuli (10, 30, 50, 70, 100, and 150 Hz). Traces in each column are recorded from the same muscle cell. In control mice (
A
), EPPs follow closely with increasing frequency of stimulation from 10–150 Hz. In UbG76V-GFP-Syb2 mice, EPPs fail to follow at high frequencies of stimulation; transmission failure first appears at 30 Hz (
B
, arrowheads point to stimulus artifact).
C
, Quantification of success rates (the percentage of EPP responses as a function of the frequency of stimulation) between control mice (open bar) and UbG76V-GFP-Syb2 transgenic mice (filled bar) at 10, 30, 50, 70, 100, and 150 Hz. With increasing stimulation frequency, the rates of successful synaptic transmission are significantly decreased in UbG76V-GFP-Syb2 mice. Control mice: n = 15 muscle fibers, N = 3 mice; UbG76V-GFP-Syb2 mice: n = 18 muscle fibers, N = 3 mice. p = 0.0107 (30 Hz); p = 0.0135 (50 Hz); p = 0.0132 (70 Hz); p = 0.0014 (100 Hz); and 1.367 × 10−8 (150 Hz).
D
, Quantification of success rates as a function of age in response to a 1 s train at 100 Hz (1 s) in control mice (open bar) and UbG76V-GFP-Syb2 mice (filled bars). The number of muscles (n) and the number of mice (N) analyzed at each age group are listed as follows: 1-month-old group: control mice, n = 15, N = 3; UbG76V-GFP-Syb2 mice, n = 15, N = 3; 3-month-old group: control mice, n = 15, N = 3; UbG76V-GFP-Syb2 mice, n = 14, N = 3, p = 0.005; 5-month-old group: control mice, n = 14, N = 3; UbG76V-GFP-Syb2 mice, n = 15, N = 3, p = 0.0089; 8-month-old group: control mice, n = 12, N = 3; UbG76V-GFP-Syb2 mice, n = 12, N = 3, p = 5.493 × 10−6; 10-month-old group: control mice, n = 15, N = 3; UbG76V-GFP-Syb2 mice, n = 15, N = 3, p = 3.891 × 10−7; 12-month-old group: control mice, n = 12, N = 3; UbG76V-GFP-Syb2 mice, n = 12, N = 3, p = 7.693 × 10−8). Calibration: the line underneath the 30 Hz example applies to both the 10 and 30 Hz traces; the line underneath the 150 Hz example applies to 50, 70, 100, and 150 Hz panels (traces represent the first 200 ms of the recording).