The muscles of humans undergo atrophy under the reduced load-bearing conditions of limb immobilization. Little is known about the effects of such atrophy on the overall operation of the functional unit of muscle, that is, the segmental motor-control system. The latter comprises four basic elements: the motoneurons supplying the atrophied musculature, the muscle units and muscle receptors (spindles and tendon organs) within the musculature and the feedback from these sensory receptors to spinal interneurons and motoneurons. Whole-muscle response to limb immobilization has been demonstrated to depend upon both muscle length and immobilization duration. The intent of the proposal is to determine the nature of the manifestation of the whole-muscle changes among its muscle-unit types and in relation to its functional associates (segmental motor-control system). The experimental animal will be the adult cat, with atrophy induced by immobilization of both hindlimbs. The test muscle will be tibialis posterior whose fiber-type composition, motor-unit properties and anatomic relationships with the spinal cord make it an ideal model for the study of atrophy. Using both control and immobilized animals, an electrophysiologic analysis will be made of: select properties of motoneurons, muscle units and muscle receptors (Aims 1-3); and, the """"""""strength"""""""" of synaptic connections between the muscle's spindle receptors and select spinal motoneurons and interneurons (Aim 4). These studies will provide information required for a better understanding of the motor-control problems of otherwise healthy subjects during and after a period of limb immobilization for an orthopedic injury. In addition, such information should give insight into the motor-control problems of patients suffering from a variety of atrophy-inducing diseases such as Duchenne Dystrophy, Limbgirdle Dystrophy, Motoneuron Disease, Myasthenia Gravis, Myotonic Dystrophy, Thyrotoxicosis, Progressive Muscular Atrophy and Spinal Muscular Atrophy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Orthopedics and Musculoskeletal Study Section (ORTH)
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University of Arizona
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Callister, Robert J; Sesodia, Sanjay; Enoka, Roger M et al. (2004) Fatigue of rat hindlimb motor units: biochemical-physiological associations. Muscle Nerve 30:714-26
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