Early Electrophysiological Abnormalities in Lumbar Motoneurons in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is a lethal, adult-onset disease characterized by progressive degeneration of motoneurons. Recent data have suggested that the disease could be linked to abnormal development of the motor nervous system. Therefore, we investigated the electrical properties of lumbar motoneurons in an in-vitro neonatal spinal cord preparation isolated from SOD1(G85R) mice, which is a transgenic model of amyotrophic lateral sclerosis. The study was performed on young animals at the beginning of their second week, between postnatal days 6 and 10. Measurements of resting membrane potential and action potential characteristics of motoneurons were similar in wild-type and SOD1(G85R) mice. However, the input resistance of motoneurons from transgenic mice was significantly lower than that of wild-type animals, whereas their membrane capacitance was increased, strongly suggesting larger SOD1(G85R) motoneurons. Furthermore, the slope of the frequency-intensity curve was steeper in motoneurons from wild-type pups. Interestingly, the input resistance as well as the slope of the frequency-intensity curves of other spinal neurons did not show such differences. Finally, the amplitude of dorsal root-evoked potentials following high-intensity stimulation was significantly smaller in SOD1(G85R) motoneurons. The superoxide dismutase 1 mutation thus induces specific alterations of the functional properties of motoneurons early in development.