Liu Lab @ HHMI Janelia
Molecular and functional diversity of lung interoceptors
As we vividly precieve the external world through the canoical five senses, our nervous system also continuously monitors our internal organs and environment. This internal monitoring is in part carried out by organ interoceptors, which are sensory neurons innervating internal organs and transmit information from the organs to the central nervous system. Sensory information transmitted by these neurons is enssential for homeostatic regulation of body physiology and for generating the higher-order brain perception of internal states, called "interoception".
As the essential organ for gas exchange, the lungs are extensively innervated by interoceptors residing in the cranial ganglia on the vagal nerve (Xth cranial nerve). Our previous work generated a comprehensive molecular atlas of lung interoceptors and defined ten molecular subtypes that differ in sensory and signaling repertoires. Intial characterizations of a few subtypes also revealed their different anatomical features and physiological functions in breathing regulation. We are going to continue this direction by generating new genetic tools and combine them with recording, imaging, opto/chemogenetic manipulations, and whole animal physiology to understand how this diverse group of interoceptors encode sensory information from the lungs and regulate breathing and cardiorespiratory physiology.
Central processing of lung sensory input
The central projections of majority, if not all, of vagal lung interoceptors target the nucleus of the solitary tract (NTS) in the brainstem, where they synapse with second-order neurons that further connect to downstream neural circuits, including the respiratory centers, the autonomic centers, and higher-order brain regions that control emotions and generate perception. With the new level of cellular diversity among lung interoceptors revealed, next questions are how is information conveyed by these neurons processed and integrated in the NTS and how is the integrated information transmitted through downstream circuits to eventually generate physiological, behavioral, and perceptual outputs. We are going to combine subtype-specific labeling and manipulations of lung interoceptors and systems neuroscience approaches to tackle these questions.
Lung-brain interaction in pulmonary diseases
When the lung is under diseased conditions, such as asthma, COPD, viral or bacterial infections, and cancer, the internal environment and signal molecules present in the organ alter substantially. This leads to activity and property changes in lung interoceptors, contributing to symptoms that affect the quality of life, such as cough and dyspnea. Moreover, this altered sensory input may also affect autonomic outputs to the cardiorespiratory system, regulating the disease progression and pathophysiology. We are interested in identifying subtypes of lung interoceptors that are affected or mediate the pathophysiology in a given disease, the critical temporal windows they function, and the underlying molecular mechanisms. We also seek to explore if and how the downstream circuits of these subtypes alter their architectures and properties.