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Foundational Mapping of the Neural Circuits that Control Intrinsic Lung Function
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A4655 - Foundational Mapping of the Neural Circuits that Control Intrinsic Lung Function
Author Block: J. Verheyden1, J. Xu1, T. Zhang1, W. Paltzer1, Y. Xu2, X. Sun3; 1Pediatrics, UC San Diego, La Jolla, CA, United States, 2Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH, United States, 3Pediatrics, University of California, San Diego, San Diego, CA, United States.
RATIONALE: The lung is a highly innervated organ. In addition to controlling breathing, by driving the contraction of the diaphragm, the neural circuits also regulate other essential aspects of lung function including airway tone, pulmonary vascular pressure and immune responses. These physiological outcomes are constantly modified by the contents of the air we breathe, which can vary in concentration of oxygen, pollutants, allergens, etc. It has been shown that these signals can activate sensory neurons with cell bodies located in the vagal ganglia and dorsal root ganglia. These signals are then relayed to the brainstem and spinal cord where they are processed into responses that control the function of pulmonary neuroendocrine cells (PNECs) in the airway epithelium and two types of smooth muscle cells (airway and vascular). The spatial organization, morphology, and molecular characteristics of these neurons, as well as precisely which functions they control, remain poorly understood.
METHODS: We used a retrograde adeno-associated virus (AAV) expressing Cre recombinase to specifically infect lungs of mice carrying a tdTomato reporter. This allowed us to infect axon projections in the lung and retrograde label the innervating neuron cell bodies in the vagal ganglia. We then performed single nuclei RNA-seq on vagal ganglia from these labeled mice. In a separate experiment, we treated mice with allergen challenge and isolated total RNA from their vagal ganglia and performed RNA-seq and qRT-PCR analysis.
RESULTS: We mapped neurons of the vagal ganglia and identified their molecular signature. The transcriptome data segregated the neurons into multiple populations, including the ones that innervate the lung. There are several categories of genes that are altered in the vagal ganglia neurons in response to allergen compared to control.
CONCLUSIONS: Our data lay the foundation for determining the characteristics and specific function of the neural circuit that innervates the lung. The long-term goal is to use this knowledge to precisely modulate lung function through these neuronal pathways.
Author Block: J. Verheyden1, J. Xu1, T. Zhang1, W. Paltzer1, Y. Xu2, X. Sun3; 1Pediatrics, UC San Diego, La Jolla, CA, United States, 2Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH, United States, 3Pediatrics, University of California, San Diego, San Diego, CA, United States.
RATIONALE: The lung is a highly innervated organ. In addition to controlling breathing, by driving the contraction of the diaphragm, the neural circuits also regulate other essential aspects of lung function including airway tone, pulmonary vascular pressure and immune responses. These physiological outcomes are constantly modified by the contents of the air we breathe, which can vary in concentration of oxygen, pollutants, allergens, etc. It has been shown that these signals can activate sensory neurons with cell bodies located in the vagal ganglia and dorsal root ganglia. These signals are then relayed to the brainstem and spinal cord where they are processed into responses that control the function of pulmonary neuroendocrine cells (PNECs) in the airway epithelium and two types of smooth muscle cells (airway and vascular). The spatial organization, morphology, and molecular characteristics of these neurons, as well as precisely which functions they control, remain poorly understood.
METHODS: We used a retrograde adeno-associated virus (AAV) expressing Cre recombinase to specifically infect lungs of mice carrying a tdTomato reporter. This allowed us to infect axon projections in the lung and retrograde label the innervating neuron cell bodies in the vagal ganglia. We then performed single nuclei RNA-seq on vagal ganglia from these labeled mice. In a separate experiment, we treated mice with allergen challenge and isolated total RNA from their vagal ganglia and performed RNA-seq and qRT-PCR analysis.
RESULTS: We mapped neurons of the vagal ganglia and identified their molecular signature. The transcriptome data segregated the neurons into multiple populations, including the ones that innervate the lung. There are several categories of genes that are altered in the vagal ganglia neurons in response to allergen compared to control.
CONCLUSIONS: Our data lay the foundation for determining the characteristics and specific function of the neural circuit that innervates the lung. The long-term goal is to use this knowledge to precisely modulate lung function through these neuronal pathways.
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