Phenotypic traits of the hypothalamic PVN cells innervating airway-related vagal preganglionic neurons.

The paraventricular nucleus of the hypothalamus (PVN) integrates multiple inputs via projections from arginine vasopressin (AVP)- and oxytocin (OXT)-containing neurons to the brain stem and spinal cord as well as regulates respiratory and cardiovascular stress-related responses, which also affect airway function. In the present study, we used immunocytochemistry and the retrograde transneuronal tracer, Bartha strain of pseudorabies virus expressing green fluorescent protein (PRV-GFP), to localize AVP- and OXT-producing neurons that project to airway-related vagal preganglionic neurons (AVPNs) innervating intrapulmonary airways. PRV-GFP was microinjected into the upper right lung lobe, and after 4 days survival, hypothalamic tissue sections were processed for co-expression of PRV-GFP and AVP or PRV-GFP and OXT. In addition, in a separate group of five rats, Phaseolus vulgaris leucoagglutinin (PHAL), an anterograde tracer, was injected unilaterally into the PVN and cholera toxin beta subunit was microinjected into the tracheal wall. Analysis of five successfully infected animals showed that 14% of PRV-GFP labeled neurons express AVP traits and 18% of transneuronally-labeled neurons contain OXT. Furthermore, the identified AVPNs innervating extrathoracic trachea receive axon terminals of the PVN neurons. The results indicate that AVP- and OXT-producing PVN cells, via direct projections to the AVPNs, could modulate cholinergic outflow to the airways, as a part of overall changes in response to stress.

CNS determinants of sleep-related worsening of airway functions: implications for nocturnal asthma.

This review summarizes the recent neuroanatomical and physiological studies that form the neural basis for the state-dependent changes in airway resistance. Here, we review only the interactions between the brain regions generating quiet (non-rapid eye movement, NREM) and active (rapid eye movement, REM) sleep stages and CNS pathways controlling cholinergic outflow to the airways. During NREM and REM sleep, bronchoconstrictive responses are heightened and conductivity of the airways is lower as compared to the waking state. The decrease in conductivity of the lower airways parallels the sleep-induced decline in the discharge of brainstem monoaminergic cell groups and GABAergic neurons of the ventrolateral periaqueductal midbrain region, all of which provide inhibitory inputs to airway-related vagal preganglionic neurons (AVPNs). Withdrawal of central inhibitory influences to AVPNs results in a shift from inhibitory to excitatory transmission that leads to an increase in airway responsiveness, cholinergic outflow to the lower airways and consequently, bronchoconstriction. In healthy subjects, these changes are clinically unnoticed. However, in patients with bronchial asthma, sleep-related alterations in lung functions are troublesome, causing intensified bronchopulmonary symptoms (nocturnal asthma), frequent arousals, decreased quality of life, and increased mortality. Unquestionably, the studies revealing neural mechanisms that underlie sleep-related alterations of airway function will provide new directions in the treatment and prevention of sleep-induced worsening of airway diseases.