Reflex increases in genioglossus (GG) muscle activity in response to negative pharyngeal pressure are important for maintenance of upper airway patency in humans. However, little is known of the central circuitry that mediates this negative pressure reflex (NPR). We used two approaches to determine which GG premotoneurons relay negative pressure-related information to the hypoglossal motor nucleus. First, to identify GG premotoneurons, we injected pseudorabies virus (PRV152) into the GG muscle. We found that medullary GG premotoneurons were concentrated mainly in the reticular formation adjacent to the hypoglossal motor nucleus. Second, in order to determine whether these perihypoglossal neurons were involved in the NPR, we quantified GG EMG responses to negative pressure applied to the isolated upper airway in anaesthetized rats before and after microinjection of muscimol (9 nl; 0.25 m m), a GABA-A receptor agonist, into the perihypoglossal premotor field. Pressures as low as - 4 cmH2O increased inspiratory phase-related GG activity. The NPR was abolished following bilateral injections of muscimol into the perihypoglossal premotor field at and up to 500 μm rostral to the obex. Muscimol in this location also increased the amplitude of basal, unstimulated phasic GG activity. By contrast, inhibition of neurons caudal to the obex decreased phasic GG activity but had no impact on the NPR. These results suggest that perihypoglossal GG premotoneurons near the obex mediate the NPR and those caudal to the obex are important mediators of respiratory-related GG activity but are not involved in the NPR.
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