MOTOR UNIT BEHAVIOR IN CANINE MOTOR-NEURON DISEASE

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomally do minant disease of motor neurons that shares many pathological features with human motor neuron disease, A particularly striking feature of t he 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 thes e 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 ac tivate muscle fibers, The tetanic forces of innervated motor units in young homozygotes tended to be smaller than those in closely age-match ed clinically normal animals, In older homozygotes (approximate to 4.5 months, postnatal), all motor neurons sampled were capable of activat ing muscle fibers, but many motor units displayed abnormal behavior in cluding an inability to sustain force output during high frequency act ivation, Motor units exhibiting tetanic failure also showed proportion ately greater twitch potentiation than nonfailing units of similar unp otentiated twitch amplitude, Tetanic failure and large potentiation te nded to occur in motor units that possessed the slowest contraction sp eeds, These results indicate that motor neuron functional defects in H CSMA appear initially in the most distal parts of the motor axon and i nvolve defective neurotransmission, The possible roles of distal nerve degeneration, motor terminal sprouting, and synaptic transmission in causing these deficits are considered.