Journal of Neuroscience, Vol 15, 3447-3457, Copyright © 1995 by Society for Neuroscience
Motor unit behavior in canine motor neuron disease
MJ Pinter, RF Waldeck, N Wallace and LC Cork
Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Hereditary canine spinal muscular atrophy (HCSMA) is an autosomally
dominant disease of motor neurons that shares many pathological features
with human motor neuron disease. A particularly striking feature of the
affected, accelerated phenotype (homozygous HCSMA) is that profound
weakness develops before appreciable motor neuron cell death occurs (Cork
et al., 1989a), implying that motor unit functional defects occur
initially. The purpose of this study was to identify the site of these
defects and characterize their nature. In most young homozygotes (2-3
months postnatal), motor neurons were encountered that could support
orthodromic action potential propagation to the muscle but did not activate
muscle fibers. The tetanic forces of innervated motor units in young
homozygotes tended to be smaller than those in closely age-matched
clinically normal animals. In older homozygotes (approximately 4.5 months,
postnatal), all motor neurons sampled were capable of activating muscle
fibers, but many motor units displayed abnormal behavior including an
inability to sustain force output during high frequency activation. Motor
units exhibiting tetanic failure also showed proportionately greater twitch
potentiation than nonfailing units of similar unpotentiated twitch
amplitude. Tetanic failure and large potentiation tended to occur in motor
units that possessed the slowest contraction speeds. These results indicate
that motor neuron functional defects in HCSMA appear initially in the most
distal parts of the motor axon and involve defective neurotransmission. The
possible roles of distal nerve degeneration, motor terminal sprouting, and
synaptic transmission in causing these deficits are considered.
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