“The Coding and Circuitry of Interoception”

Chen Ran, PhD
Assistant Professor
Department of Neuroscience
The Scripps Research Institute

Our senses of sight, smell, taste, touch and hearing allow us to perceive the external physical world. The internal sensory systems, by contrast, enable the brain to receive signals from within the body to generate our internal senses, such as hunger, satiety, thirst, nausea, hypoxia and visceral pain. How does the brain differentiate hunger pangs from the feeling of fullness? Or the sense of nausea when toxins are ingested? Why does stomach stretch lead to satiety while bladder stretch produces the urge to urinate?

To understand these questions, the Chan Lab developed a novel in vivo two-photon mouse brainstem calcium imaging platform. This system allowed them, for the first time, to record the activities of thousands of neurons, with single-cell resolution, in the brain’s gateway to the internal organs. The lab delivered different types of stimuli in the animal’s internal organs, mimicking the stretch of the stomach, ingestion of nutrients, pain in the organs and many others, and watched how different populations of neurons respond to these stimuli. The lab’s previous work revealed that internal organs are topographically represented in the brainstem, forming a “visceral homunculus.”

Combining in vivo functional imaging, electrophysiological recordings and mouse genetics, neuronal activity manipulation (optogenetics, chemogenetics), animal behavior, neural circuit tracing and others, the lab will unravel how the nervous system detects mechanical, chemical and thermal stimuli from the periphery to synthesize our internal sensations, such as satiety, hunger, nausea, hypoxia and visceral pain. Discoveries from the lab’s research will reveal basic principles of how the brain encodes and processes information and shed light on the development of novel therapeutics for treating hypertension, obesity, diabetes, indigestion, eating disorders, pulmonary diseases, nausea, visceral pain, infection-induced sickness behaviors and many others.