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Single nuclei sequencing of the nodose ganglia

ABSTRACT: The vagus nerves are important carriers of sensory information from the viscera to the brain. Emerging evidence suggests that sensory signaling through the right, but not the left, vagus nerve evokes striatal dopamine release and reinforces appetitive behaviors. However, the extent to which differential gene expression within vagal sensory neurons may underlie this asymmetric reward-related signaling is unknown. Here, we use single-nucleus RNA sequencing, in situ hybridization, and calcium imaging to identify a single cluster of neurons, defined by co-expression of Chrna3 (nicotinic acetylcholine receptor subunit 3) and Cckar (cholecystokinin 1 receptor), that is preferentially expressed in the right nodose ganglia of rats. This neuronal population also expresses several genes implicated in digestive signaling, including Glp1r and Sctr, consistent with a gut-innervating subtype. Our results suggest that right-biased expression of this unique chemosensing vagal cell type may contribute to asymmetric encoding of interoceptive rewards by the vagus nerves.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE280062 | GEO | 2024/11/01

REPOSITORIES: GEO

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Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.

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Single nuclei sequencing of the nodose ganglia

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