The overall research goal is to investigate postnatal development of fast synaptic transmission to hypoglossal motoneurons (HMs) and modulation of this transmission by serotonin (5-HT). HMs innervate the tongue muscle and therefor are critically important in regulation of upper airway patency. The upper airway is a site of airway obstruction; thus a comprehensive understanding of the development of systems that synaptically excite and inhibit HMs may provide new insights into certain pathologic states, including apnea of prematurity, Sudden Infant Death Syndrome and obstructive sleep apnea. Preliminary data show that during the postnatal period marked changes occur in both excitatory (primarily involving N-methyl-D-aspartate - NMDA) and inhibitory (glycinergic) synaptic responses of HMs. It is hypothesized that these changes are due to postsynaptic mechanisms involving alterations in the respective ligand-gated channels. This proposal focuses on in vitro studies of visualized rat HMs in brainstem slices, and uses whole-cell and single-channel recordings from HMs. The first three specific aims investigate developmental changes in NMDA synaptic current.
The first aim i s to quantify changes in evoked, spontaneous and postsynaptic NMDA currents, as well as in single NMDA channel properties.
The second aim i s to investigate the mechanism(s) for the reduction in NMDA synaptic current in older versus younger HMs. It is hypothesized that various factors including NMDA, Mg++ and glycine sensitivities account for these differences.
The third aim i nvestigates postnatal developmental changes in 5-HT1B receptor activated inhibition of glutamatergic synaptic transmission. The final two specific aims investigate developmental changes in glycinergic synaptic currents.
Aim four quantifies the developmental changes that occur in evoked, spontaneous and postsynaptic glycinergic currents in HMs, as well as in single glycine channel properties. The fifth aim investigates postnatal changes in 5-HT1B receptor activated inhibition of glycinergic synaptic transmission. A knowledge of these developmental changes in synaptic inputs may have important functional and pathological implications for control of tongue muscle and therefore upper airway patency.
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