DEVELOPMENTAL CONTROL OF THE DIAPHRAGM AND UPPER AIRWAYS

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DESCRIPTION (Adapted from the applicant's abstract): This proposal will characterize the postnatal development of the genioglossal and phrenic motoneurons, by correlating physiological changes in membrane conductance and spiking properties with changes in anatomy. The strength of respiratory muscle contraction is determined by the number of respiratory motoneurons activated and their rate of discharge. Both the order in which the neurons are activated and their discharge rates are a function of their resting conductance, that is, the number of membrane channels open at any given time. Most membrane channels are controlled by neurotransmitters and/or by the intrinsic electrical state of the cell membrane. The change in the balance of these two processes are most dramatic during postnatal development. The applicant is interested in these processes that occur in the two respiratory motoneurons that affect the performance of the diaphragm and genioglossus. Activation of these two muscles must be coordinated to move air into the lungs with the least effort; this may be particularly relevant to the pathophysiology of Sudden Infant Death Syndrome (SIDS). In the past period, the applicant established that glycine significantly contributed to the increase in resting membrane conductance that occurs at 3 weeks, and that these age-related increases in resting conductance result from an increase in the number of open potassium channels. The proposed studies will be performed on genioglossal and phrenic motoneurons in slice preparations of the rat brainstem and spinal cord. Visually identified motoneurons will be studied from four different age groups (1-2, 5-7, 13-15 and 19-22 days) with a combination of patch-clamp recording, three-dimensional neuronal reconstruction and immunocytochemical localization of certain receptors and ion channels. The application will: 1) examine the anatomy and physiology of glycine, GABA, and glutamate neurotransmitter systems at the four stages during postnatal development; 2) identify specific potassium channels that contribute to the increase in membrane conductance and spike characteristics; and 3) explore the intracellular pathways mediating the enhanced potassium conductance.