Zhuang J, Xu F, Frazier DT. Hyperventilation evoked by activation of the vicinity of the caudal inferior olivary nucleus depends on the fastigial nucleus in anesthetized rats. J Appl Physiol 104: 1351-1358, 2008. First published March 20, 2008 doi:10.1152 doi:10. /japplphysiol.00824.2007eral studies have demonstrated that cerebellar deep nuclei, particularly the rostral fastigial nucleus (FNr), are involved in respiratory modulation. These nuclei receive inputs from the contralateral caudal inferior olivary nuclei of the medulla. The objectives of this study were to determine whether electrical and chemical activation of the vicinity of the caudal inferior olivary nuclei (vIOc) affected respiration and, if true, whether the FNr was involved in the vIOc stimulation-evoked ventilatory responses. Experiments were conducted in 30 anesthetized and spontaneously breathing rats. Our results showed that 1) electrical (25 or 100 A at 10 or 20 Hz for 10 s) and chemical (1 or 100 mM, 25-50 nl N-methyl-D-aspartate) stimulation of the vIOc augmented ventilation predominantly via increasing tidal volume; 2) the responses to the electrical stimulation were almost eliminated by lesion of the contralateral FNr via microinjection of ibotenic acid; and 3) the respiratory responses to electrical stimulation in the vicinity of the rostral IO were 65-70% smaller compared with that evoked by vIOc stimulation. These findings strongly suggest that vIOc neurons play a significant role in modulation of respiratory activity, largely depending on their projections to the FNr. cerebellum; sudden infant death syndrome; inferior olive projections; hypertension THE INFERIOR OLIVARY NUCLEUS (IO), a nucleic complex located ventromedially in the medulla oblongata, has been amply documented to play important roles in motor functions, e.g., motor coordination and motor learning (2, 14) and visceral renal functions (28,40). Recent evidence from clinical observations has implied a possible IO involvement in cardiorespiratory dysfunction. First, victims of sudden infant death syndrome, a sleep apnea syndrome precipitated by defective control of involuntary respiration, often show neurotransmitter receptor deficiencies (10), developmental abnormalities (16), and prominent neuropathological changes in the IO (15). Second, a specific neuronal loss in the IO was found in infants with severe perinatal asphyxia (36). Third, a tremendous alteration of c-Fos immunoreactivity was found in the IO of asphyxia rather than nonasphyxia cases, with the effects more specific than in any other region related to respiration (29). Expression of the fos gene in neuronal nuclei has been proposed to reflect second-messenger activation and, hence, serves as a sensitive indicator of cellular responses induced by various stimuli. In concert with the clinical observations, the possible role of the caudal IO (IOc) in cardiorespiratory modulation has also been reported in animals. For example, electrical stimulation to the IOc was reported to cause an apnea in anesthetized cats ...