Résumé :
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In Amyotrophic Lateral Sclerosis (ALS; SOD1 G93A model), only the fast contracting motor units are affected [1,2]. The mechanisms leading to this selective vulnerability are still unknown. In particular, we do not know whether the motoneurons' (MNs) electrophysiological properties are affected when muscle fiber denervation starts. In this study, we investigated whether spinal MNs of ALS mice model (SOD1 G93A mice) display abnormal sub-threshold and firing properties in the course of the disease, i.e. just before or during the degeneration process. We performed intracellular recordings of 25 lumbar MNs in anesthetized SOD1 G93A mice aged from P39 to P70 (same preparation as in [3]). The mean input resistance was 2.1 ± 0.8 M (SD, range 1.1-4.3 M, n=23) and the mean membrane time constant was 1.7 ± 1.1 ms (range 0.4-3.8 ms, n=18), i.e. respectively 43% and 32% smaller than in wild type (WT; see [3]) mice. While the time constant values of SOD1 MNs were distributed in the WT range, our sample lacked high input resistance values. All other sub-threshold properties tested (electrotonic length: 1.3 ± 0.3, range 0.8-1.9, n=15; cell capacitance: 1.2 ± 0.8 nF, range 0.2-2.8 nF, n=15; subthreshold resonance frequency: 16 ± 4 Hz, range 9-22 Hz, n=13) were not statistically different from WT mice (see [3]). The discharge properties were tested in 13 MNs using slow triangular current ramps (1-2 nA/s). 3 MNs were unresponsive. 9 displayed fast sub-threshold oscillations between action potentials, which characterize the sub-primary firing range recently described in WT mice [3]. This range was followed (6 MNs) or not (3 MNs) by a linear primary range (i.e., no oscillation between spikes) as in WT animals. In contrast to WT, one SOD1 MN did not display fast oscillations. The mean gain of the primary range (15 ± 4 Hz/nA, range 9-20 Hz/nA, n=7) was similar to WT MNs. In conclusion, when neuromuscular junctions begin to degenerate, only the input resistance and the membrane time constant were significantly reduced in SOD1 mice with respect to WT. The firing properties were rather similar. Since our sample may contain MNs innervating both, affected and unaffected motor units, it is now necessary to find criteria, which will allow differentiating the two classes of MNs.
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