A multidimensional coding architecture of the vagal interoceptive system

• Published in: Nature (London) Vol. 603; no. 7903; pp. 878 - 884
• Main Authors: Zhao, Qiancheng, Yu, Chuyue D., Wang, Rui, Xu, Qian J., Dai Pra, Rafael, Zhang, Le, Chang, Rui B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-03-2022; Nature Publishing Group
• Subjects: 14/19; 14/32; 14/35; 14/63; 14/69; 45/91; 631/378/1959/1315; 631/378/3917; 631/443/376; 64/60; Animals; Bar codes; Brain; Brain - metabolism; Brain stem; Calcium - metabolism; Calcium imaging; Combinatorial analysis; Communications systems; Computer architecture; Gene expression; Humanities and Social Sciences; Infections; Mammals - metabolism; Mice; Modules; multidisciplinary; Neural coding; Neuroimaging; Organs; Perception; Physiology; Psychophysiology; Science; Science (multidisciplinary); Sensory neurons; Sensory Receptor Cells - metabolism; Small intestine; Stomach; Topography; Transcriptomics; Vagus Nerve; Viral infections; Vomeronasal Organ
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-022-04515-5

Interoception, the ability to timely and precisely sense changes inside the body, is critical for survival
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. Vagal sensory neurons (VSNs) form an important body-to-brain connection, navigating visceral organs along the rostral–caudal axis of the body and crossing the surface–lumen axis of organs into appropriate tissue layers
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. The brain can discriminate numerous body signals through VSNs, but the underlying coding strategy remains poorly understood. Here we show that VSNs code visceral organ, tissue layer and stimulus modality—three key features of an interoceptive signal—in different dimensions. Large-scale single-cell profiling of VSNs from seven major organs in mice using multiplexed projection barcodes reveals a ‘visceral organ’ dimension composed of differentially expressed gene modules that code organs along the body’s rostral–caudal axis. We discover another ‘tissue layer’ dimension with gene modules that code the locations of VSN endings along the surface–lumen axis of organs. Using calcium-imaging-guided spatial transcriptomics, we show that VSNs are organized into functional units to sense similar stimuli across organs and tissue layers; this constitutes a third ‘stimulus modality’ dimension. The three independent feature-coding dimensions together specify many parallel VSN pathways in a combinatorial manner and facilitate the complex projection of VSNs in the brainstem. Our study highlights a multidimensional coding architecture of the mammalian vagal interoceptive system for effective signal communication.
Single-cell profiling of vagal sensory neurons from seven organs in mice and calcium-imaging-guided spatial transcriptomics reveal that interoceptive signals are coded through three distinct dimensions, allowing efficient processing of multiple signals in parallel using a combinatorial strategy.