Electrical Activity in the Neuromuscular Unit Can Influence the Molecular Development of Motor Neurons

Abstract

During the first few weeks of postnatal life spinal motor neurons develop electrophysiological, morphological, and molecular features that are characteristic of adult motor neurons. To understand how the acquisition of the mature neuronal phenotype is regulated, we have examined the expression of the motor neuron cell surface proteoglycan recognized by monoclonal antibody Cat-301 in the hamster. Previously we found that Cat-301 immunoreactivity is not present on motor neurons at birth and that by the end of the second postnatal week all motor neurons are Cat-301-positive. Surgical and pharmacological lesion studies have shown that the onset of Cat-301 expression depends upon input from both large-diameter primary afferents and from supraspinal afferents. Once the Cat-301 proteoglycan is expressed on motor neurons, its continued expression is independent of these inputs. These studies suggested that motor neuron maturation depends upon the coordination of several afferent inputs during the first postnatal weeks of life. Our previous studies could not address whether segmental and descending afferents (i) provide a chemical signal (such as a trophic factor) or (ii) confer a pattern of neuronal activity upon motor neurons that then results in the expression of the Cat-301 proteoglycan. The present experiments examine the role of electrical activity in motor neuron maturation. In normal animals, all sciatic motor neurons are Cat-301-positive by Postnatal Day 19 (P19). Chronic application of the sodium channel blocker, tetrodotoxin (TTX), to the sciatic nerve in neonatal animals reduces the percentage of Cat-301-positive motor neurons found at P21 by one-third. This reduction is not due to a nonspecific inhibition of all protein synthesis, because the expression of two other motor neuron antigens proceeds normally in TTX-treated neonates. Blockade of neuromuscular transmission in neonates by Botulinus toxin A also reduces the percentage of Cat-301-positive motor neurons. Cat-301 expression is not tied simply to neuronal activity, because chronic application of TTX to the sciatic nerve, or Botulinus toxin A to muscles, in the adult does not reduce Cat-301 expression. These findings indicate that electrical activity generated within the neuromuscular unit in early postnatal life can influence the acquisition of mature molecular properties by motor neurons.