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This review summarizes recent work on two basic processes of central nervous system (CNS) control of cholinergic outflow to the airways: 1) transmission of bronchoconstrictive signals from the airways to the airway-related vagal preganglionic neurons (AVPNs) and 2) regulation of AVPN responses to excitatory inputs by central GABAergic inhibitory pathways. In addition, the autocrine-paracrine modulation of AVPNs is briefly discussed. CNS influences on the tracheobronchopulmonary system are transmitted via AVPNs, whose discharge depends on the balance between excitatory and inhibitory impulses that they receive. Alterations in this equilibrium may lead to dramatic functional changes. Recent findings indicate that excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second-order neurons within the nucleus of the solitary tract (NTS), via a glutamate-AMPA signaling pathway. These neurons, using the same neurotransmitter-receptor unit, transmit information to the AVPNs, which in turn convey the central command to airway effector organs: smooth muscle, submucosal secretory glands, and the vasculature, through intramural ganglionic neurons. The strength and duration of reflex-induced bronchoconstriction is modulated by GABAergic-inhibitory inputs and autocrine-paracrine controlling mechanisms. Downregulation of GABAergic inhibitory influences may result in a shift from inhibitory to excitatory drive that may lead to increased excitability of AVPNs, heightened airway responsiveness, and sustained narrowing of the airways. Hence a better understanding of these normal and altered central neural circuits and mechanisms could potentially improve the design of therapeutic interventions and the treatment of airway obstructive diseases.

The present study was carried out to determine whether dorsal raphe serotonergic neurons are involved in the regulation of suckling-induced PRL release. Neurotoxin lesions were placed stereotaxically in lactating rats on day 1 of lactation by 5,7-dihydroxytryptamine microinjection into the dorsal raphe (DR), median raphe (MR), or superior colliculus (SC), an area devoid of serotonergic perikarya. Litters were adjusted to eight pups each and weighed daily to determine litter growth rates. On day 7 of lactation, litters were separated from mothers for 8 h, after which six healthy foster pups were provided for a 30-min suckling stimulus. Animals were killed by decapitation immediately after suckling, plasma was collected for RIA of PRL, and brains were frozen and dissected for determination of hypothalamic, caudate, and hippocampal serotonin (5-HT) using the enzymatic-isotopic assay procedure. Litter growth rates from days 1-7 of lactation were significantly different among lesion groups (P less than 0.005), with litters from SC-lesioned animals (SCL) growing similarly to the sham group (sham, 0.924; SCL, 0.941 g/pup . day). In contrast, growth rates of litters from both DR-lesioned (DRL) and MR-lesioned (MRL) animals were significantly depressed (DRL, 0.596; MRL, 0.449 g/pup . day; P less than 0.05 and P less than 0.01, respectively). 5-HT levels in hypothalamus, caudate nuclei, and hippocampus were similar in the sham and SCL groups, whereas hypothalamic 5-HT was depleted by 63% and 55%, respectively, in the DRL and MRL groups. Despite impairments in growth rate and litter survival in both the DRL and MRL groups, only DRL animals showed significant decrements in suckling-induced PRL release (DRL, 288 +/- 107; sham, 837 +/- 134 ng NIAMDD rat PRL RP-1/ml; P less than 0.05) after 5-HT-depleting lesions. The results suggest a specificity of function within the raphe system during lactation; DR 5-HT neurons which project to the hypothalamus provide stimulatory inputs to suckling-induced PRL release, whereas MR 5-HT neurons influence litter growth and survival via their role in maternal behavior.