Mapping of sensory nerve subsets within the vagal ganglia and the brainstem using reporter mice for Pirt, TRPV1, 5HT3 and Tac1 expression

Abstract

Vagal afferent sensory nerves, originating in jugular and nodose ganglia, are comprised of functionally distinct subsets whose activation evokes distinct thoracic and abdominal reflex responses. We used Cre-expressing mouse strains to identify specific vagal afferent populations and map their central projections within the brainstem. We show that Pirt is expressed in virtually all vagal afferents; whereas 5HT3 is expressed only in nodose neurons, with little expression in jugular neurons. TRPV1, the capsaicin receptor, is expressed in a subset of small nodose and jugular neurons. Tac1, the gene for tachykinins, is expressed predominantly in jugular neurons, some of which also express TRPV1. Vagal fibers project centrally to the nucleus tractus solitarius (nTS), paratrigeminal complex, area postrema and to a limited extent the dorsal motor nucleus of the vagus. nTS subnuclei preferentially receive projections by specific afferent subsets, with TRPV1+ fibers terminating in medial and dorsal regions predominantly caudal of obex, whereas TRPV1-negative fibers terminate in ventral and lateral regions throughout the rostral-caudal aspect of the medulla. Many vagal Tac1+ afferents (mostly derived from the jugular ganglion) terminate in the nTS. The paratrigeminal complex was the target of multiple vagal afferent subsets. Importantly, lung-specific TRPV1+ and Tac1+ afferent terminations were restricted to the caudal medial nTS, with no innervation of other medulla regions. In summary, this study identifies the specific medulla regions innervated by vagal afferent subsets. The distinct terminations provide a neuroanatomic substrate for the diverse range of reflexes initiated by vagal afferent activation.

Significance statement Vagal afferents transmit sensory information from visceral organs to the brainstem, where their activity alters sensation and visceral reflexes. Vagal afferents are comprised of distinct subsets which serve distinct functions. Little is known of the neuroanatomy of central projections of distinct vagal subsets, thus there remains an incomplete understanding of how visceral events evoke appropriate behavioral and reflex responses. This precludes rationally-developed pharmacological or electroceutical interventions to modify aberrant sensations/reflexes. Here, we used cell-specific reporter expression to identify the brainstem pathways of distinct vagal afferent subsets. We show that TRPV1+ vagal afferents innervate ipsilateral and contralateral dorsal/medial nTS subnuclei and the ipsilateral paratrigeminal complex, whereas TRPV1-negative vagal afferents innervate the ipsilateral rostral/ventral/lateral nTS subnuclei and the ipsilateral paratrigeminal complex.