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An atlas of vagal sensory neurons and their molecular specialization

ABSTRACT: An atlas of vagal sensory neurons and their molecular specialization

PROVIDER: PRJNA511592 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8367081.fastq.gz	Fastqsanger.gz
	SRR8367082.fastq.gz	Fastqsanger.gz
	SRR8367083.fastq.gz	Fastqsanger.gz
	SRR8367084.fastq.gz	Fastqsanger.gz

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An atlas of vagal sensory neurons and their molecular specialization

Project description:Sensory functions of the vagus nerve are critical for specific aware perceptions and for monitoring visceral functions in the cardio-pulmonary and gastrointestinal systems. Here we present a comprehensive identification, classification, and validation of the neuron types in the neural crest (jugular) and placode (nodose) derived vagal ganglia by single cell transcriptomic (scRNA-seq) analysis. Our results reveal major differences between neurons derived from different embryonic origins. Jugular neurons exhibit fundamental similarities to the somatosensory spinal neurons, including major types such as C-low threshold mechanoreceptors (C-LTMRs), A-LTMRs, Aδ-nociceptors, cold-, and mechano-heat C-nociceptors. In contrast, the nodose ganglion contains 18 distinct types dedicated to surveying the physiological state of the internal body. Our results reveal a vast diversity of vagal neuron types including many previously unanticipated types as well as proposed types that are consistent with chemoreceptors, nutrient detectors, baroreceptors, and stretch and volume mechanoreceptors of the respiratory, gastrointestinal, and cardiovascular systems.

2019-05-20 | GSE124312 | GEO

Transcriptional profiling of individual airway projecting vagal sensory neurons

Project description:Mammalian airways and lungs are richly innervated by bronchopulmonary sensory neurons, the vast majority of which are derived from the vagal sensory ganglia. In the present study we set out to perform high coverage single cell RNA sequencing on a population of identified murine bronchopulmonary sensory neurons collected from the vagal sensory ganglia to better define the molecular expression profiles of these cell types. Given the importance of P2X2 in differentiating nodose from jugular sensory neurons, we further aimed to investigate the relationship between transcriptional expression of identified genes and P2X2 expression.

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Project description:Influenza A virus (IAV) is rapidly detected in the airways by the immune system, with resident parenchymal cells and leukocytes orchestrating viral sensing and the induction of antiviral inflammatory responses. The airways are innervated by heterogenous populations of vagal sensory neurons which also play an important role in pulmonary defense. How these neurons respond to IAV respiratory infection remains unclear. Here, we use a murine model to provide the first evidence that vagal sensory neurons undergo significant transcriptional changes following a respiratory IAV infection. RNA sequencing on vagal sensory ganglia showed that IAV infection induced the expression of many genes associated with an antiviral and pro-inflammatory response

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Project description:Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.

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Project description:The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In a mouse model of colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication.

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