Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced beta-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)-deficient motoneurons exhibit severe defe...

The influence of neurotrophins on motoneuron survival and development has been well documented in cell cultures and neonates. In the present study, the role of brain-derived neurotrophic factor (BDNF) in the maintenance of motoneuron electrical properties was investigated. In adult male rats, BDNF- or saline-saturated gelfoam was inserted between the medial and lateral heads of the gastrocnemiu...

ALS (amyotrophic lateral sclerosis) is an adult-onset and deadly neurodegenerative disease characterized by a progressive and selective loss of motoneurons. Transgenic mice overexpressing a mutated human gene (G93A) coding for the enzyme SOD1 (Cu/Zn superoxide dismutase) develop a motoneuron disease resembling ALS in humans. In this generally accepted ALS model, we tested the electrophysiologic...

Development of motoneuron electrical properties and excitability was studied in spinal cord explants of rat embryos cultured for 1-3 weeks. The morphological organization of the spinal cord and synaptic inputs onto motoneurons were maintained in organ culture. The rate of differentiation of motoneuron resting potential and increase in membrane excitability was similar in vitro and in vivo, sugg...

To effect movement, motoneurons must respond appropriately to motor commands. Their responsiveness to these inputs, or excitability, is regulated by neuromodulators. Possible sources of modulation include the abundant cholinergic "C boutons" that surround motoneuron somata. In the present study, recordings from motoneurons in spinal cord slices demonstrated that cholinergic activation of m2-typ...

Motoneuron hyperexcitability is a characteristic of several different motor disorders. We examined neuronal mechanisms of hyperexcitability in two of these disorders: spasticity after spinal cord injury (SCI) and bruxism. Involuntary muscle spasms after SCI occur as a result of uncontrolled increases in motoneuron excitability. Brainstem-derived serotonin (5HT) and noradrenaline (NA) normally f...