Decoding the Molecular, Cellular, and Functional Heterogeneity of Zebrafish Intracardiac Nervous System

The proper functioning of the heart relies on the intricate interplay between the central nervous system and the local neuronal networks within the heart itself. While the central innervation of the heart has been extensively studied, the organization and functionality of the intracardiac nervous system (IcNS) remain largely unexplored. Here, we present a comprehensive taxonomy of the IcNS, utilizing single-cell RNA sequencing, anatomical studies, and electrophysiological techniques. Our findings reveal a diverse array of neuronal types within the IcNS, exceeding previous expectations. We identify a subset of neurons exhibiting characteristics akin to pacemaker/rhythmogenic neurons similar to those found in Central Pattern Generator networks of the central nervous system. Our results underscore the heterogeneity within the IcNS and its key role in regulating the heart's rhythmic functionality. The classification and characterization of the IcNS presented here serve as a valuable resource for further exploration into the mechanisms underlying heart functionality and the pathophysiology of associated cardiac disorders.