We propose to continue studies that examine the functional and structural organization of the hypoglossal (XIIth) nucleus with reference to the contractile properties (as measured by a strain gauge system) and electromyography (EMG) of the individual tongue muscles (i.e., the extrinsic genioglossus, styloglossus and hypoglossus muscles, plus the various intrinsic tongue muscles). The experiments will consist of three basic phases and are to be performed on totally anesthetized rats. 1) Anatomical studies using isolated nerve/muscle preparations will be done. Each of the three surgically isolated extrinsic muscles, in separate experiments, will be injected with the highly specific cholera toxin horseradish peroxidase conjugate (CTHRP) in order to retrogradely label the motoneuron (MN) pools for each muscle. These MNs will be classified according to their specific location within the XIIth nucleus, the total number of cells labeled and size as measured by cell body diameter. The final labeling study will involve the intrinsic muscles. The detailed findings from this approach should alleviate the current lack of knowledge and confusion regarding the myotopic organization of the hypoglossal nucleus. 2) Whole muscle and motor unit contractile properties will be studied, again using our isolated nerve/muscle preparations. Localized stimulation of antidromically identified MNs within a particular area of the hypoglossal nucleus will elicit contractions of one of the muscles while EMG recordings of the other extrinsic (or intrinsic) muscles will serve as controls to indicate which MN pool we are examining. The contractile characteristics studied will include twitch contraction time, fusion frequency, twitch tension, maximum tetanic tension and fatigue so that motor units can be classified according to type. 3) In conjunction with """"""""2"""""""" above, hypoglossal motor unit recruitment will be assessed through stimulation of cortical sites known to evoke various tongue movements. The response hierarchy of antidromically identified motoneurons (within particular motoneuron pools), and their muscle units, to cortical stimulation will be assessed. These studies should lay a foundation for understanding how the XIIth nucleus is organized with respect to the forces produced in the tongue. Informed patient treatment and an understanding of the tongue muscle's complex movement patterns are possible only after its neuromuscular components have been delineated.
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