The cerebellum contains three deep nuclei, i.e., the fastigial, interposed and lateral nucleus. Recent studies demonstrate that these nuclei play different roles in respiratory modulation. Activation of fastigial nuclear neurons predominantly increases ventilation via elevation of respiratory frequency and/or tidal volume. Ablation of the fastigial nucleus did not significantly alter eupneic breathing, but did markedly attenuate the respiratory response to medium and severe hypercapnia as well as hypoxia. The fastigial nucleus contains respiratory-modulated neurons and about 25% of these neurons do not show their respiratory-related phasic activity until exposed to hypercapnia. The fastigial nucleus also contains CO2/H+ chemosensitive sites that contributed to the respiratory response to hypercapnia. Therefore, it is concluded that fastigial nuclear facilitatory influence on chemoreflexes emerges during hypercapnia via recruiting intrinsic chemoreception and respiratory-modulated neurons. Full expression of the fastigial nucleus-mediated respiratory responses depends on the integrity of the medullary gigantocellular nucleus at least partially via monosynaptic projections. Additionally, the fastigial nucleus receives inhibitory inputs primarily from Purkinje cells located in the medial vermis and recent observations indicate that simulation of these Purkinje cells inhibits respiration. As compared to chemoreflexes, fastigial nuclear role in the respiratory mechanoreflexes is not significant. The studies related to the role of the interposed and lateral nucleus in eupneic breathing are limited and the results appear controversial. However, there is evidence to show that the interposed nucleus contains respiratory-modulated neurons and is involved in coughing motor control.

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3-5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7-1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.

The present study was undertaken to determine what roles the various cerebellar deep nuclei (CDN) play in modulation of respiration, especially during chemical challenges. Experiments were carried out in 12 anesthetized, tracheotomized, paralyzed, and ventilated rats. The integrated phrenic nerve activity (integralPN) was recorded as an index of respiratory motor output. A stimulating electrode was sequentially placed into the fastigial nucleus (FN), the interposed nucleus, and the lateral nucleus. Only stimulation of the FN significantly altered respiration, primarily via increasing respiratory frequency associated with a pressor response. The evoked respiratory responses persisted after blocking the pressor response via pretreatment with phenoxybenzamine or use of transient stimulation (<2 s) but were abolished by microinjection of kainic acid into the FN. To test the involvement of FN neurons in respiratory chemoreflexes, ventilation with hypercapnic gases mixture and intravenous injection of sodium cyanide were applied before and after CDN lesions induced by kainic acid. CDN lesions did not significantly alter eupneic breathing, but FN lesions attenuated the respiratory response to hypercapnia and sodium cyanide. We conclude that, with respect to the CDN in the rat, FN neurons uniquely modulate respiration independent of cardiovascular effects and facilitate respiratory responses mediated by activation of CO(2) and O(2) receptors.

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