Muscimol inhibition of medullary raphé neurons decreases the CO2 response and alters sleep in newborn piglets.

Medullary raphé neurons are chemosensitive in vitro (Wang et al., J. Physiol. Lond. 511 (1998)), are involved in the ventilatory response to CO(2) in vivo (Dreshaj et al., Respir. Physiol. 111 (1998); Nattie and Li, J. Appl. Physiol. 90 (2001)), and are abnormal in many Sudden Infant Death Syndrome (SIDS) victims (Panigrahy et al., J. Neuropathol. Exp. Neurol. 59 (2000)). In this study we determine whether the ventilatory response to CO(2) is altered when medullary raphé neuronal function is focally and reversibly inhibited in chronically instrumented newborn piglets. Ventilation was measured by whole body plethysmography in room air and in 5% CO(2) before and during microdialysis of muscimol, a gamma-amino butyric acid (GABA(A)) receptor agonist, into the medullary raphé. Muscimol (10 mM in the dialysate), had no effect on eupneic ventilation, but reduced significantly the CO(2) response by 17% during wakefulness. Sleep cycling was also disrupted, as characterized by a significant increase in the percentage of time spent awake and a significant decrease in the percentage of time spent in NREM sleep. Disturbances of medullary raphé function can alter central chemoreception and normal sleep architecture, which may contribute to the pathogenesis of SIDS.