This work characterizes the properties of wild-type (WT) mouse motoneurons in the second postnatal week and compares these at the same age and in the same conditions to those of two different SOD1 mutant lines used as models of human amyotrophic lateral sclerosis (ALS), the SOD1(G93A) low expressor line and SOD1(G85R) line, to describe any changes in the functional properties of mutant motoneurons (Mns) that may be related to the pathogenesis of human ALS. We show that very early changes in excitability occur in SOD1 mutant Mns that have different properties from those of WT animals. The SOD1(G93A-Low) low expressor line displays specific differences that are not found in other mutant lines including a more depolarized membrane potential, larger spike width, and slower spike rise slope. With current pulses SOD1(G93A-Low) were hyperexcitable, but both mutants had a lower gain with current ramps stimulation. Changes in the threshold and intensities of Na(+) and Ca(2+) persistent inward currents were also observed. Low expressor mutants show reduced total persistant inward currents compared with WT motoneurons in the same recording conditions and give arguments toward modifications of the balance between Na(+) and Ca(2+) persistent inward currents. During the second week postnatal, SOD1(G93A-Low) lumbar motoneurons appear more immature than those of SOD1(G85R) compared with WT and we propose that different time course of the disease, possibly linked with different toxic properties of the mutated protein in each model, may explain the discrepancies between excitability changes described in the different models.
1. Ninety-seven spinal motoneurones were identified by their antidromic invasion following stimulation of the muscle nerve and submitted to a series of four tests to reveal a possible direct excitation between motoneurones. 2. Threshold differentiation, refractoriness, hyperpolarization and collision revealed antidromically induced depolarizations in fourteen of the ninety-seven tested motoneurones. 3. The parameters of the antidromically induced depolarizations indicate a short latency, a low amplitude and independence with regard to the membrane polarization. 4. It is concluded that the antidromically induced depolarizations reached the impaled motoneurone via a route other than its own axon. 5. The mechanism may involve either electrotonic interactions between neighbouring motoneurones or excitatory recurrent collaterals between synergist motoneurones.
We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance (Rin) and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest Rin and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained). The delayed onset firing type has the highest rheobase and the fastest action potential (AP) whereas the transient firing group has the lowest rheobase and the less mature AP. We found 32 and 10% of motoneurons with a transient firing at P3–P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3–P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis) are the most preponderant at P6–P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis) emerge at P8–P9. The emergence of types 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week of life in mice.
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