Distinct Organization of Upper Airway Nodose and Jugular Vagal Circuits in the Brain: Evidence from Conditional Anterograde Transneuronal Tracing and Physiology

Abstract

Irritations of the airways evoke brainstem‐mediated reflex changes in breathing and complex sensorimotor responses dependent upon ascending inputs to higher brain centers. Airway vagal afferents terminate in the nucleus of the solitary tract (Sol) and the paratrigeminal nucleus (Pa5) however, whether these nuclei are comparable in terms of afferent inputs, central ascending projections or physiological function is unknown. In Sprague‐Dawley rats (n=4) retrograde tracing with fluorescently tagged cholera toxin B revealed neurons in the jugular vagal ganglia project predominately to the Pa5, while nodose vagal ganglia neurons terminate in the Sol. Electrical stimulation of the trachea in urethane anesthetized rats evoked stimulus dependent apneic responses (control n=4; Emax reduction in respiratory rate = 3±2 breaths/min) which were abolished after inhibition of the Sol by microinjection of GABAA agonist, muscimol (n=4, Emax = 62±5, p=0.001), but only partially inhibited from the Pa5 (n=5; Emax = 36±6, p=0.01). To determine the ascending projections of airway specific Sol and Pa5 neurons we constructed a conditional HSV‐1 H129 virus that switches fluorescent reporters in the presence of Cre allowing the connectivity of subsets of neurons to be visualized. Following inoculation of the airways with HSV‐1 H129, the Sol (n=8) projected to the zona incerta, paraventricular and lateral hypothalamic nuclei, while Pa5 (n=7) neurons terminated in the submedius and ventrobasal thalamus. Taken together, these data suggest distinct pathways governing airway sensations exist, likely playing differing roles in the processing of respiratory responses.