The research is concerned with the hypothesis that muscle regulates or maintains the functional properties of adult motoneurons. This hypothesis derives from results showing that when the connection between muscle and motoneuron is broken by axotomy, the normal gradation of membrane properties among motoneurons is lost. Other findings indicate that the normal functional organization of motoneuron pools depends upon the existence of this gradation.
The specific aim of the proposed work is to explore the hypothesis that many of the effects of axotomy are due to a loss of trophic influences of muscle or motoneuron. This will be accomplished by exploring the mechanisms by which axotomy causes the disruption in motoneuron properties. Intracellular recording from identified cat spinal motoneurons will be used to compare the effects of chronic axotomy with those that result: 1) when axonal transport between motoneurons and muscle is blocked; and 2) when transmitter-release from motor terminals is chronically blocked by intra-muscularly-injected botulinum toxin. Also, the importance of re-establishing neuromuscular synaptic contact in the recovery of motoneuron functional properties after axotomy will be assessed by allowing the axons to regenerate into the muscle but preventing the formation of synaptic contact with muscle fibers. The results will provide the basis for distinguishing those effects of axotomy that result from disruption of trophic influence from those that are the consequence of axonal injury and will also provide information concerning the means by which muscle may regulate motoneuron membrane properties. If muscle is involved in the regulation of motoneuron properties, then it is not unreasonable to suppose that disruptions in this influence may lead to motoneuron pathology. Information concerning the role of muscle in regulating normal motoneuron properties may enhance our understanding of motoneuron diseases and help to devise strategies for intervention.
| Vanden Noven, S; Wallace, N; Muccio, D et al. (1993) Adult spinal motoneurons remain viable despite prolonged absence of functional synaptic contact with muscle. Exp Neurol 123:147-56 |
| Pinter, M J; Vanden Noven, S; Muccio, D et al. (1991) Axotomy-like changes in cat motoneuron electrical properties elicited by botulinum toxin depend on the complete elimination of neuromuscular transmission. J Neurosci 11:657-66 |
| Pinter, M J; Vanden Noven, S (1989) Effects of preventing reinnervation on axotomized spinal motoneurons in the cat. I. Motoneuron electrical properties. J Neurophysiol 62:311-24 |
| Vanden Noven, S; Pinter, M J (1989) Effects of preventing reinnervation on axotomized spinal motoneurons in the cat. II. Changes in group Ia synaptic function. J Neurophysiol 62:325-33 |
