Reflex regulation of breathing by the paratrigeminal nucleus via multiple bulbar circuits
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Sensory neurons of the jugular vagal ganglia innervate the respiratory tract and project to the poorly studied medullary paratrigeminal nucleus. In the present study, we used neuroanatomical tracing, pharmacology and physiology in guinea pig to investigate the paratrigeminal neural circuits mediating jugular ganglia-evoked respiratory reflexes. Retrogradely traced laryngeal jugular ganglia neurons were largely (> 60%) unmyelinated and expressed the neuropeptide substance P and calcitonin gene-related peptide, although a population (~ 30%) of larger diameter myelinated jugular neurons was defined by the expression of vGlut1. Within the brainstem, vagal afferent terminals were confined to the caudal two-thirds of the paratrigeminal nucleus. Electrical stimulation of the laryngeal mucosa evoked a vagally mediated respiratory slowing that was mimicked by laryngeal capsaicin application. These laryngeal reflexes were modestly reduced by neuropeptide receptor antagonist microinjections into the paratrigeminal nucleus, but abolished by ionotropic glutamate receptor antagonists. d,l-Homocysteic acid microinjections into the paratrigeminal nucleus mimicked the laryngeal-evoked respiratory slowing, whereas capsaicin microinjections evoked a persistent tachypnoea that was insensitive to glutamatergic inhibition but abolished by neuropeptide receptor antagonists. Extensive projections from paratrigeminal neurons were anterogradely traced throughout the pontomedullary respiratory column. Dual retrograde tracing from pontine and ventrolateral medullary termination sites, as well as immunohistochemical staining for calbindin and neurokinin 1 receptors, supported the existence of different subpopulations of paratrigeminal neurons. Collectively, these data provide anatomical and functional evidence for at least two types of post-synaptic paratrigeminal neurons involved in respiratory reflexes, highlighting an unrecognised complexity in sensory processing in this region of the brainstem.
KeywordsLaryngeal reflexes Jugular vagal ganglia Airway afferents Neural crest Respiratory sensation
This research was supported by Grants to Dr. SB Mazzone and Dr MJ Farrell from the National Health and Medical Research Council (NHMRC) of Australia .
AKD conducted experiments, contributed to drafting and editing the manuscript. MJF contributed to experimental design and manuscript editing. AEM conducted experiments, contributed to drafting and editing manuscript. SBM conceived experiments, contributed to writing and editing of the manuscript. All authors contributed to the interpretation of the data.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
Animals were housed in a standard environment and given ad libitum access to water and food. All animal experiments were approved by an accredited institutional Animal Ethics Committee.
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