Motor Control of Diaphragm Muscle

Our laboratory is generally interested in the area of neuromotor control of skeletal muscle contraction, with particular emphasis on neural control of the diaphragm muscle. As in other skeletal muscles, the diaphragm is composed of functional units (motor units),each comprised of a motoneuron and the muscle fibers innervated by the motoneuron. In our studies, we have shown that diaphragm motor units vary considerably in their physiological and metabolic properties. This functional diversity among motor units ensures that a variety of motor behaviors can be accomplished by controlling how and when motor units are recruited. For example, in effective breathing movements, the nervous system must be very selective as to which units are recruited since some motor units are very susceptible to fatigue. In situations requiring greater force generation by the diaphragm, such as gagging, sneezing and vomitting, the nervous system recruits larger motor units which are more fatigable. Based on the repertoire of available motor units, we have modelled how the nervous system controls motor unit recruitment during different ventilatory and non-ventilatory behaviors of the diaphragm.

The neural control of skeletal muscle is fine-tuned through interactions between the motoneuron and innervated muscle fibers. For example, a motoneuron exerts a direct trophic influence over the enzymatic properties of muscle fibers, thus influencing muscle fiber metabolism and the expression of contractile proteins. In addition, muscle fibers adapt to alterations in activation by either increasing or decreasing their metabolic capacities. This metabolic plasticity is the basis for muscle adaptations to exercise or inactivity. In the case of ventilatory muscles such as the diaphragm, adaptations to altered use can have very important clinical implications. For example, patients with emphysema are exposed to a chronic mechanical load which imposes a form of endurance exercise on the ventilatory muscles. In other cases where patients are maintained on mechanical ventilators, the activity of breathing muscles is decreased. In Duchenne muscular dystrophy, there is a selective loss of larger, fatigable diaphragm muscle fibers, which necessitates motor unit reorganization, and thus a restructuring of the recrutiment pattern of the diaphragm. Our laboratory is examining the bases for such plasticity in diaphragm neuromotor control in response to conditions of altered use.

In other studies, we are examining plasticity in diaphragm neuromotor control associated with postnatal development. The pattern of diaphragm muscle innervation changes markedly during postnatal development. Furthermore, the functional demands placed on the breathing muscles also vary considerably, requiring adaptations in the recruitment pattern of diaphragm motor units as the animal matures. The adaptations in diaphragm neuromotor control somehow match these rapidly changing functional demands.Overall, the laboratory makes use of a number of animal models to address the issue of plasticity in neuromotor control:

  • Spinal Cord Injury
  • Nerve Blockade
  • Denervation
  • Compensatory Loading
  • Postnatal development
  • Corticosteroid Treatment
  • Hypothyroidism
  • Muscular Dystrophy
Our studies evaluate plasticity at every level of neuromotor control: the diaphragm muscle, the neuromuscular junction on diaphragm muscle fibers, and the phrenic motoneurons that control the diaphragm. In these studies, we make use of a number of state-of-the-art techniques:
  • Multicolor Immunocytochemistry
  • 3D Confocal Microscopy of the Neuromuscular Junctions and Motoneurons
  • Real-Time 4D Confocal Imaging of Cellular Events
  • Real-Time Fluorescence Imaging of Intracellular Calcium, pH and ATPase Activity
  • Computer-based Microphotometry to Measure Muscle Metabolism
  • Neurophysiological Procedures to Study Muscle Contraction and Fatigue, and Neuromuscular Transmission Failure
  • Intracellular Electrophysiology
  • Isometric and Isotonic Properties of Single Muscle Fibers
  • Gel Electrophoresis and Western Analysis
  • Molecular Biology of Muscle Proteins

See samples of recent work