Research & Publications
Like the splendid external world, the environment inside our body is constantly changing. The ability to monitor internal organ status by the nervous system is essential, ensuring an appropriate regulation of physiology and behavior to diverse body needs. What signals are critical for this communication between body organs and the brain? How are different organ cues being detected and processed? Are these pathways altered under certain disease conditions? The Chang lab uses state-of-the-art molecular, genetic, and imaging approaches including single-cell gene expression profiling, virus-based anatomical tracing, in vivo imaging, optogenetics, and chemogenetics to functionally dissect out diverse organ-to-brain circuits. Our goal is to better understand the important body-brain interface, and to develop novel neuronal-based therapeutic strategies for disease intervention.
Extensive Research Description
The vagus nerve is a major conduit between body and brain that relays critical sensory information from the neck, chest, and abdomen, and controls basic autonomic functions of the respiratory, cardiovascular, digestive, and immune systems. Surgical, electrical, or pharmacological control of vagus nerve activity impacts numerous diseases. Our previous studies demonstrated that the vagus nerve contains intermingled sensory neurons constituting genetically definable labeled lines with different anatomical connections and physiological roles. Sensory neuron populations that control breathing and digestion were identified using a molecular deconstruction of the vagus nerve, and such information facilities our understanding of molecular mechanisms for physiological reflexes.
The Chang lab is currently focusing on the neural pathways that control cardiovascular physiology. We approach this topic from three different angles.
1. Vagal Cardiovascular neurons and disease.
Vagal neurons represent gatekeepers in the neural regulation of cardiovascular functions, yet their physiological roles in health and disease remain elusive. We use AAV-guided anatomical mapping, in vivo calcium imaging, and optogenetics to genetically define and characterize vagal neurons that interact with the cardiovascular system.
2. Central sensory mechanisms that regulate cardiovascular physiology.
A molecular and cellular dissection of neural circuits for diverse cardiovascular reflexes is a first step towards understanding the neural mechanisms of cardiovascular regulation. We use state-of-the-art genetic tools to establish a complete circuit-wiring paradigm for cardiovascular reflexes.
3. Dissect neural circuits for cardiovascular reflexes.
Sensory neurons in the circumventricular organs (CVOs) that lack a normal blood-brain barrier are excellent candidates for receiving body vital signals like hormones, electrolytes, and metabolites from the bloodstream. We use genetic approaches to functionally dissect sensory CVO neurons, with a focus on neuron types that control cardiovascular physiology.
Cardiovascular System; Cranial Nerves; Heart; Neural Pathways; Physiology; Vagus Nerve; Peripheral Nervous System; Ganglia, Sensory; Optogenetics