Abstract
In amyotrophic lateral sclerosis (ALS) the large motoneurons that innervate the fast-contracting muscle fibers (F-type motoneurons) are vulnerable and degenerate in adulthood. In contrast, the small motoneurons that innervate the slow-contracting fibers (S-type motoneurons) are resistant and do not degenerate. Intrinsic hyperexcitability of F-type motoneurons during early postnatal development has long been hypothesized to contribute to neural degeneration in the adult. Here, we performed a critical test of this hypothesis by recording from identified F- and S-type motoneurons in the superoxide dismutase-1 mutant G93A (mSOD1), a mouse model of ALS at a neonatal age when early pathophysiological changes are observed. Contrary to the standard hypothesis, excitability of F-type motoneurons was unchanged in the mutant mice. Surprisingly, the S-type motoneurons of mSDO1 mice did display intrinsic hyperexcitability (lower rheobase, hyperpolarized spiking threshold). As S-type motoneurons are resistant in ALS, we conclude that early intrinsic hyperexcitability does not contribute to motoneuron degeneration.
Highlights
Glutamate excitotoxicity has long been suggested to contribute to the degeneration of motoneurons in amyotrophic lateral sclerosis
Regardless of its effect, it is still not clear whether spinal motoneurons are hyperexcitable in mutant superoxide dismutase 1 mice, a standard model of amyotrophic lateral sclerosis (ALS)
We show that only spinal motoneurons that display the immediate firing pattern undergo substantial electrical and morphological alterations in neonatal mutant superoxide dismutase 1 (mSOD1) mice whereas no changes occur in the motoneurons displaying the delayed firing pattern
Summary
Glutamate excitotoxicity has long been suggested to contribute to the degeneration of motoneurons in amyotrophic lateral sclerosis. Regardless of its effect, it is still not clear whether spinal motoneurons are hyperexcitable in mutant superoxide dismutase 1 (mSOD1) mice, a standard model of amyotrophic lateral sclerosis (ALS). Martin et al (2013) found, in an in vitro preparation of mSOD1 embryonic cord, that motoneurons are hyperexcitable: their dendritic tree is reduced causing an increase in input resistance. Pambo–Pambo et al (2009) did not observe any change in spinal motoneuron input resistance, rheobase, or stationary gain suggesting that their excitability was unchanged. In the same line, Quinlan et al (2011) found that the excitability of spinal motoneurons is homeostatically maintained despite an increase in their input conductance (recruitment current and F–I gain unchanged). Bories et al (2007) reported a decrease in input resistance causing the spinal motoneurons to be hypoexcitable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
