In a new study published in Journal of Comparative Neurology, researchers in Dr. Cheng’s lab at the University of Central Florida (UCF) have for the first time mapped the spinal afferent innervation of the rat heart. Cardiac sensory information is transmitted through two primary pathways: vagal afferents from the nodose ganglia and spinal afferents from the dorsal root ganglia. While spinal afferents are crucial for detecting and relaying pain signals, they are less studied than their vagal counterparts (Cheng et al., 1997). Previously, this team used a novel anterograde tracing technique to label spinal afferent innervation of the rat stomach (Ma et al., 2023). Now, this advanced tracing method has been adapted to label spinal afferent projection to the heart.
Detailed imaging showed the axons forming simple to complex terminal structures in various layers, including the epicardium and myocardium but rarely the endocardium, while structurally interacting with cardiac muscles, blood vessels, and fat tissues. These findings enable researchers to compare terminal structures and their targets of spinal and vagal afferents in different layers of the atrium, which increases our understanding of the distinct innervation patterns of these sensory pathways.
This detailed map of cardiac spinal afferent innervation establishes an anatomical foundation for further functional studies of this pathway and its remodeling in heart diseases. Furthermore, the use of this anterograde tracer technique opens new possibilities to explore spinal afferent innervation in other visceral organs.
Figure 1: Anterograde labeling of a single spinal afferent axon with extensive branch arborization in the left atrium. (a) Contour of a representative left atrium and the location of a single axon within the atrium. (a’) Neurolucida tracing of the axon. The parent axon (PA) is indicated with a black arrow. (a’1) A rotational view of the Neurolucida tracing in (a’) (a’1; counterclockwise y: 800). The red circles in (a’) and (a’1) mark the first bifurcation point of this PA. Landmarks, including red arrowheads, red arrows and red circles, designate the exact corresponding positions of the tracing from different angles in (a’) and (a’1), respectively. (b,c,d) Partial projections corresponding to the same letters in (a’) showed the parent axon near epicardial adipose tissue (b) and its varicose branches innervating the cardiac muscle (c and d). Free terminals are observed in (d) (black arrows), and in (a’) and a’1) (red arrowheads). LAu, left-atrium auricle; PV, pulmonary vein; AT, adipose tissue; CM, cardiac muscle; Epi, epicardium; Myo, myocardium.
Figure 2: Schematic representation of terminal structures and targets of spinal and vagal afferents in different layers of the rat atrium. Both spinal and vagal afferents project to all three layers: epicardium (Epi), myocardium (Myo), and endocardium (Endo). In the Epi, spinal afferents make some close contacts with cardiac ganglionic neurons and adipose tissue, whereas vagal afferents selectively form pericellular terminal structures around small intensely fluorescent (SIF) cells without innervating any cardiac ganglionic neurons. In the Myo, spinal afferents display a range of axonal structures, from simple to complex branching patterns, whereas vagal afferents form specialized intramuscular endings. In the Endo, some spinal afferents branch into free nerve endings, whereas vagal afferents form many distinct terminal “flower-sprays” and end-nets. The illustration was partially created with Biorender components (https://www.biorender.com/).
References:
Cheng Z, Powley TL, Schwaber JS, Doyle FJ 3rd. Vagal afferent innervation of the atria of the rat heart reconstructed with confocal microscopy. J Comp Neurol. 1997 Apr 28;381(1):1-17. doi: 10.1002/(sici)1096-9861(19970428)381:1<1::aid-cne1>3.0.co;2-5. PMID: 9087415.
Ma J, Nguyen D, Madas J, Kwiat AM, Toledo Z, Bizanti A, Kogut N, Mistareehi A, Bendowski K, Zhang Y, Chen J, Li DP, Powley TL, Furness JB, Cheng Z. Spinal afferent innervation in flat-mounts of the rat stomach: anterograde tracing. Sci Rep. 2023 Oct 18;13(1):17675. doi: 10.1038/s41598-023-43120-y. PMID: 37853008; PMCID: PMC10584867.
