Figure 6.

Some cells are hypoexcitable and cannot fire repetitively. A, Example of an mSOD1 motoneuron (from a P88 mouse) that is unable to fire repetitively in response to a triangular ramp of current. Top trace, Membrane potential. Bottom trace, Injected current. B, This same motoneuron was nevertheless able to generate a single full-height AP in response to a square pulse of current. Same organization as in A. C, Voltage-clamp measurement of the PICs in this same motoneuron. Traces are (from top to bottom), leak current (dashed line), raw current (blue), leak-subtracted current (red), and voltage command (green). D, Non-firing motoneurons had a similar input conductance compared with motoneurons capable of firing repetitively. Firing: 0.49 ± 0.22 μS, N = 47 versus non-firing: 0.38 ± 0.20 μS, N = 6; g = −0.54 95%CI[−1.11–0.50]; t₍₅₁₎ = 1.36, p = 0.22. E, Non-firing motoneurons had much smaller PICs than motoneurons able to fire repetitively. Firing: 4.04 ± 3.18 nA, N = 47 versus non-firing: 0.60 ± 0.49 nA, N = 6; g = −1.12 95%CI[−1.42–−0.86]; t₍₅₁₎ = 6.81, ****p = 1.3e−08. F, Non-firing motoneurons appear earlier in mSOD1 animals compared with WT animals. WT: 100 ± 16 d old, N = 7 versus SOD1: 75 ± 23 d old, N = 6; g = −1.20 95%CI[−2.06–0.01]; t₍₁₁₎ = 2.24, p = 0.053.