Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis
- Paris Descartes University, France
Figures
Figure 1 with 1 supplement
Electrical and morphological properties of motoneurons displaying the delayed and the immediate firing patterns.
(A1) WT motoneuron displaying the delayed firing pattern in response to a 5 s pulse. The current intensity was the minimal intensity necessary to elicit firing in our searching protocol (rheobase). …
Figure 1—figure supplement 1
In delayed firing motoneurons, the delay depends on the intensity of stimulation.
(A–D) Responses of a delayed firing motoneuron to long lasting pulses (5 s) of increasing amplitude. Bottom: injected-current (square pulses in nA). Top: voltage-response (in mV). Note that the …
Figure 2
immediate and delayed firing motoneurons both receive VGlut1 inputs and express NeuN.
(A) Vglut1 (red) synaptic inputs are apposed to neurobiotin (green) filled motoneurons (examples of appositions pointed by arrowheads in the inserts that show enlargements of the areas surrounded by …
Figure 3
Immediate firing motoneurons, but not delayed firing motoneurons, express ERRβ.
(A) Examples of Errβ. staining (red) in neurobiotin (green) filled motoneurons. The arrowhead in the first row points to the nucleus (Errβ−positive) of the recorded motoneuron. The asterisk in the …
Figure 4
The largest delayed firing motoneurons express chondrolectin mRNA contrary to immediate firing motoneurons.
(A) Examples of chondrolectin in situ hybridizations (red) in neurobiotin filled motoneurons (green). The asterisks in the first and third rows indicate that the cell body of the recorded motoneuron …
Figure 5
The largest delayed firing motoneurons express MMP9 contrary to immediate firing motoneurons.
(A) Examples of MMP9 labelling in neurobiotin filled motoneurons (green). The asterisks in the first and third rows indicate the cell body of the recorded motoneurons devoid of MMP9 expression. The …
Figure 6
mSOD1 immediate firing motoneurons are selectively hyperexcitable.
(A1-2) mSOD1 motoneurons displaying the delayed firing pattern (A1) and the immediate firing pattern (A2). The current intensity was the minimal intensity necessary to elicit firing (rheobase). …
Figure 7 with 1 supplement
Absence of mixed mode oscillations in mSOD1 immediate firing motoneurons.
Beginning of the discharge during the injection of slow triangular ramp of current at 0.1 nA/s velocity. See Figure 7—figure supplement 1 for the full traces and F–I curves. Arrowheads point to …
Figure 7—figure supplement 1
Responses of a delayed firing motoneuron (upper row) and of an immediate firing motoneuron (lower row) to a slow current ramp.
Same motoneurons as in Figure 7. (A1–A2) WT delayed firing motoneuron. (A1) Bottom: injected-current (slow triangular ramp at the 0.1 nA/s velocity) and top: voltage-response. (A2) F–I curves for …
Figure 8
The dendritic tree of immediate firing motoneurons is shrunk in mSOD1 mice.
(A1-2) Reconstructed dendritic trees of mSOD1 delayed (A1) and immediate (A2) firing motoneurons. The axons were not reconstructed. (B1-2) Plots of total dendritic length as a function of number of …
Tables
Table 1
Electrophysiological properties
| WT mice | mSOD1 mice | p-value | ||
|---|---|---|---|---|
| Resting membrane potential (mV) | Delayed firing | −64 ± 3 | −65 ± 3 | 0.2 |
| −70/−56 | −70/−59 | |||
| N = 63 | N = 31 | |||
| Immediate firing | −65 ± 3 | −64 ± 2 | 0.2 | |
| −71/−59 | −70/−60 | |||
| N = 31 | N = 18 | |||
| p-value | 0.3 | 0.1 | ||
| Input conductance (nS) | Delayed firing | 52 ± 28 | 54 ± 30 | 0.8 |
| 10/151 | 22/153 | |||
| N = 63 | N = 31 | |||
| Immediate firing | 33 ± 24 | 33 ± 16 | 0.6 | |
| 6/98 | 6/62 | |||
| N = 31 | N = 18 | |||
| p-value | 0.0007 | 0.01 | ||
| Rheobase (nA) | Delayed firing | 1.2 ± 0.6 | 1.1 ± 0.5 | 0.4 |
| 0.3/2.8 | 0.3/2.6 | |||
| N = 57 | N = 30 | |||
| Immediate firing | 0.6 ± 0.4 | 0.3 ± 0.2 | 0.008 | |
| 0.05/1.6 | 0.1/0.6 | |||
| N = 29 | N = 16 | |||
| p-value | <0.0001 | <0.0001 | ||
| Voltage threshold for spiking (mV) | Delayed firing | −33 ± 7 | −31 ± 10 | 0.7 |
| −47/−17 | −50/−10 | |||
| N = 58 | N = 30 | |||
| Immediate firing | −44 ± 7 | −49 ± 6 | 0.03 | |
| −50/−41 | −50/−30 | |||
| N = 30 | N = 17 | |||
| p-value | <0.0001 | <0.0001 | ||
| Voltage threshold for spiking–Resting membrane potential (mV) | Delayed firing | 31 ± 8 | 33 ± 10 | 0.4 |
| 17/49 | 13/50 | |||
| N = 59 | N = 31 | |||
| Immediate firing | 20 ± 7 | 14 ± 5 | 0.005 | |
| 8/31 | 6/21 | |||
| N = 30 | N = 17 | |||
| p-value | <0.0001 | <0.0001 | ||
| Recruitment current on ramp (nA) | Delayed firing | 1.1 ± 0.6 | 1.1 ± 0.5 | 0.8 |
| 0.1/2.8 | 0.3/2.5 | |||
| N = 51 | N = 29 | |||
| Immediate firing | 0.6 ± 0.5 | 0.3 ± 0.3 | 0.02 | |
| 0.07/2 | 0.07/1 | |||
| N = 25 | N = 15 | |||
| p-value | 0.001 | <0.0001 | ||
| Action potential amplitude (mV) | Delayed firing | 89 ± 13 | 87 ± 11 | 0.5 |
| 66/121 | 71/111 | |||
| N = 29 | N = 19 | |||
| Immediate firing | 84 ± 11 | 81 ± 15 | 0.4 | |
| 66/104 | 61/110 | |||
| N = 21 | N = 13 | |||
| p-value | 0.2 | 0.2 | ||
| Action potential width (ms) | Delayed firing | 1.4 ± 0.5 | 1.3 ± 0.4 | 0.6 |
| 0.7/2.5 | 0.6/2.2 | |||
| N = 29 | N = 19 | |||
| Immediate firing | 1.7 ± 0.4 | 1.8 ± 0.6 | 0.7 | |
| 1.1/2.9 | 0.9/3.1 | |||
| N = 21 | N = 13 | |||
| p-value | 0.04 | 0.01 | ||
| AHP relaxation time constant (ms) | Delayed firing | 27 ± 9 | 23 ± 5 | 0.2 |
| 11/50 | 15/34 | |||
| N = 21 | N = 12 | |||
| Immediate firing | 42 ± 12 | 48 ± 27 | 1 | |
| 21/60 | 19/91 | |||
| N = 11 | N = 7 | |||
| p-value | 0.004 | 0.02 | ||
Table 2
Morphological properties
| WT mice | mSOD1 mice | p-value | ||
|---|---|---|---|---|
| Soma area (µm2) | Delayed firing | 630 ± 160 | 620 ± 140 | 0.2 |
| 350/1000 | 270/890 | |||
| N = 60 | N = 31 | |||
| Immediate firing | 530 ± 180 | 454 ± 110 | 0.2 | |
| 260/940 | 250/640 | |||
| N = 30 | N = 17 | |||
| p-value | 0.009 | 0.0002 | ||
| Primary dendrites | Delayed firing | 6.4 ± 2.0 | 6.7 ± 1.2 | 0.3 |
| 4/12 | 5/9 | |||
| N = 14 | N = 14 | |||
| Immediate firing | 6.3 ± 2.7 | 6.4 ± 4.0 | 0.9 | |
| 3/10 | 2/13 | |||
| N = 10 | N = 5 | |||
| p-value | 1 | 0.5 | ||
| Total dendritic length (mm) | Delayed firing | 8.3 ± 2.9 | 8.7 ± 3.8 | 0.9 |
| 2.3/14 | 3.8/16.5 | |||
| N = 14 | N = 14 | |||
| Immediate firing | 5.3 ± 1.5 | 3.6 ± 0.3 | 0.01 | |
| 3.0/8.0 | 3.3/4.1 | |||
| N = 10 | N = 5 | |||
| p-value | 0.01 | 0.0003 | ||
| Dendritic paths (µm) | Delayed firing | 296 ± 135 | 293 ± 139 | 0.8 |
| 5/687 | 15/840 | |||
| N = 653 | N = 449 | |||
| Immediate firing | 252 ± 141 | 181 ± 157 | <0.0001 | |
| 11/803 | 11/685 | |||
| N = 281 | N = 180 | |||
| p-value | <0.0001 | <0.0001 | ||
| Terminal segments length (µm) | Delayed firing | 112 ± 93 | 108 ± 102 | 0.5 |
| 4/457 | 3/742 | |||
| N = 618 | N = 447 | |||
| Immediate firing | 108 ± 91 | 81 ± 92 | 0.001 | |
| 5/545 | 4/584 | |||
| N = 296 | N = 178 | |||
| p-value | 0.6 | 0.001 | ||
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Note that the ‘overbranching motoneuron’ (arrowhead on Figure 8B1) is excluded for analysis.
Additional files
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Supplementary file 1
Source data for Tables 1 and 2 and Figures 6 and 8.
Each sheet begins with a description of the properties measured and where they are displayed in the article.
- https://doi.org/10.7554/eLife.04046.015
