title: Distinct brainstem and forebrain circuits receiving tracheal sensory neuron inputs revealed using a novel conditional anterograde transsynaptic viral tracing system.
abstract: Sensory nerves innervating the mucosa of the airways monitor the local environment for the presence of irritant stimuli and, when activated, provide input to the nucleus of the solitary tract (Sol) and paratrigeminal nucleus (Pa5) in the medulla to drive a variety of protective behaviors. Accompanying these behaviors are perceivable sensations that, particularly for stimuli in the proximal end of the airways, can be discrete and localizable. Airway sensations likely reflect the ascending airway sensory circuitry relayed via the Sol and Pa5, which terminates broadly throughout the CNS. However, the relative contribution of the Sol and Pa5 to these ascending pathways is not known. In the present study, we developed and characterized a novel conditional anterograde transneuronal viral tracing system based on the H129 strain of herpes simplex virus 1 and used this system in rats along with conventional neuroanatomical tracing with cholera toxin B to identify subcircuits in the brainstem and forebrain that are in receipt of relayed airway sensory inputs via the Sol and Pa5. We show that both the Pa5 and proximal airways disproportionately receive afferent terminals arising from the jugular (rather than nodose) vagal ganglia and the output of the Pa5 is predominately directed toward the ventrobasal thalamus. We propose the existence of a somatosensory-like pathway from the proximal airways involving jugular ganglia afferents, the Pa5, and the somatosensory thalamus and suggest that this pathway forms the anatomical framework for sensations arising from the proximal airway mucosa.
authors.affiliation: School of Biomedical Sciences and.
authors.forename: Alice E
authors.initials: AE
authors.lastname: McGovern
authors.affiliation: School of Biomedical Sciences and.
authors.forename: Alexandria K
authors.initials: AK
authors.lastname: Driessen
authors.affiliation: School of Biomedical Sciences and.
authors.forename: David G
authors.initials: DG
authors.lastname: Simmons
authors.affiliation: Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland, Australia 4072.
authors.forename: Joseph
authors.initials: J
authors.lastname: Powell
authors.affiliation: Clinical Medical Virology Centre/Queensland Children's Medical Research Centre, the University of Queensland and Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Queensland, Australia 4029, and.
authors.forename: Nicholas
authors.identifier: http://orcid.org/0000-0001-7368-1925
authors.initials: N
authors.lastname: Davis-Poynter
authors.affiliation: Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, Victoria, Australia 3800.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0003-4126-8911
authors.initials: MJ
authors.lastname: Farrell
authors.affiliation: School of Biomedical Sciences and s.mazzone@uq.edu.au.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Mazzone
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000737:chemistry / Q000502:physiology*; D018259:Herpesvirus 1, Human; D008297:Male; D009415:Nerve Net / Q000737:chemistry / Q000502:physiology*; D056347:Neuroanatomical Tract-Tracing Techniques / Q000379:methods*; D016548:Prosencephalon / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000737:chemistry / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D014132:Trachea / Q000737:chemistry / Q000294:innervation / Q000502:physiology*
keywords: HSV-1 H129; airway sensations; neuroanatomical tracing; nucleus of the solitary tract; paratrigeminal; visceral sensation