A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system

Abstract

We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion - the right atrial ganglionic plexus (RAGP) that is a critical mediator of vagal control of the sinoatrial node (SAN) activity. We developed a 3D representation of RAGP with extensive mapping of neurons and used neuronal tracing to identify the spatial distribution of the subset of neurons that project to the SAN. RNAseq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to CNS neuronal subtypes. High-throughput qPCR of hundreds of laser capture microdissected single neurons led to a surprising finding that cholinergic and catecholaminergic neuronal markers Th and Chat were correlated, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. Interestingly, no single gene or module was an exclusive marker of RAGP neuronal connectivity to SAN. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP, informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.

3D single cell scale anatomical map of sex-dependent variability of the rat intrinsic cardiac nervous system

“…The ICNS neurons utilize a variety of neurotransmitters and modulators and receive the inputs of both local afferent and extrinsic autonomic (parasympathetic and sympathetic) nerves, performing very complicated integration in controlling cardiac functions ( Achanta et al., 2020 ; Ardell and Armour, 2016 ; Hanna et al., 2021 ; Moss et al., 2021 ). We previously identified multiple clusters of ICNS neurons on the epicardium of the superior surface of the heart and on the posterior left atrium ( Achanta et al., 2020 ; Ai et al., 2007 ; Cheng et al., 1999 ; Lin et al., 2008 ; Pauza et al., 2000 ; Richardson et al., 2003 ).…”