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Molecular Disambiguation of Heart Rate Control by the Nucleus Ambiguus

ABSTRACT: The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. Yet, how these cardiovagal nAmb neurons differ from other nAmb neurons in the adult brain remains unclear. We therefore classified adult male and female mouse nAmb neurons molecularly, anatomically, and functionally. First, our integrated analysis of single-nucleus RNA-sequencing data predicted multiple molecular subtypes of nAmb neurons. Mapping the axon projections of one nAmb neuron subtype, Npy2r-expressing nAmb neurons, showed that they innervate cardiac ganglia but not the upper airways or esophagus. Chemogenetically stimulating Npy2r+ nAmb neurons robustly decreased heart rate through peripheral muscarinic acetylcholine receptors. Finally, voluntary underwater diving decreases heart rate and activates Npy2r+ nAmb neurons, consistent with a cardiovagal function for this nAmb subtype. These results together reveal the molecular organization of nAmb neurons and its control of heart rate.

ORGANISM(S): Mus musculus

PROVIDER: GSE348348 | GEO | 2026/09/27

REPOSITORIES: GEO

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