Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”

An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs.

How does your brain recognize when it’s time to take a breath, when your blood pressure has fallen, or when your body is fighting an infection? The key lies in interoception, a little-known process through which the nervous system constantly monitors and interprets internal signals to keep essential body functions stable.

Researchers from Scripps Research and the Allen Institute have been awarded the National Institutes of Health (NIH) Director’s Transformative Research Award to develop the first comprehensive map, or atlas, of this internal sensory network.

The project will be led by Nobel Prize–winning neuroscientist Ardem Patapoutian, in collaboration with Li Ye, the N. Paul Whittier Chair in Chemistry and Chemical Biology at Scripps Research, and Bosiljka Tasic, Director of Molecular Genetics at the Allen Institute. Xin Jin, Associate Professor at Scripps Research, will serve as co-investigator and head the genomic and cell-type identification portion of the project. The initiative is supported by $14.2 million in NIH funding over the next five years.

“My team is honored that the NIH is supporting the kind of collaborative science needed to study such a complex system,” says Patapoutian, the Presidential Endowed Chair in Neurobiology at Scripps Research.

Decoding the Signals Within

Patapoutian, who shared the 2021 Nobel Prize in Physiology or Medicine for discovering cellular sensors of touch, will use the NIH award with his team to decode interoception.

“We hope our results will help other scientists ask new questions about how internal organs and the nervous system stay in sync,” adds Ye. Like Patapoutian, he’s also a Howard Hughes Medical Institute Investigator.

Established in 2009, the Transformative Research Award supports interdisciplinary projects that cross conventional boundaries and open new directions in science. This accolade is part of the NIH Common Fund’s High-Risk, High-Reward Research program, which promotes ideas aimed at filling major gaps in our understanding of human health—the kind of endeavors that might struggle to gain funding through traditional channels.

Unlike classic senses, such as smell, sight, and hearing—which are external and rely on specialized sensory organs—interoception operates through a network of neural pathways that monitor functions like circulation, digestion, and immune activity. Because these signals come from deep within the body and are often processed outside conscious awareness, interoception is often described as our “hidden sixth sense.”

Despite its importance, interoception has been historically neglected because of its complexity. Signals from internal organs spread widely, often overlap, and are difficult to isolate and measure. Sensory neurons that carry these messages weave through tissues—ranging from the heart and lungs to the stomach and kidneys—without clear anatomical boundaries.

Building the First Interoceptive Atlas

With support from the NIH, the team will chart how sensory neurons connect to a wide range of internal organs, including the heart and gastrointestinal tract. Using their findings, the researchers aim to build a comprehensive atlas that anatomically and molecularly catalogs these neural pathways.

The anatomical part of the project will label sensory neurons and then apply whole-body imaging to follow their paths from the spinal cord into different organs, generating a detailed 3D map of the routes and branching patterns. In the molecular component, the team will use genetic profiling to identify the various cell types of sensory neurons—for example, showing how neurons that send signals from the gut differ from those linked to the bladder or fat. Together, these complementary datasets will produce the first standardized framework for mapping the body’s internal sensory wiring.

By decoding interoception, the team also hopes to uncover core principles of body-brain communication that could guide new approaches to treating disease. Dysregulation of interoceptive pathways has been implicated in conditions ranging from autoimmune disorders and chronic pain to neurodegeneration and high blood pressure.

“Interoception is fundamental to nearly every aspect of health, but it remains a largely unexplored frontier of neuroscience,” says Jin, who’s a Howard Hughes Medical Institute Freeman Hrabowski Scholar. “By creating the first atlas of this system, we aim to lay the foundation for better understanding how the brain keeps the body in balance, how that balance can be disrupted in disease, and how we might restore it.”

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