Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies

• Published in: Nature communications 2019-04, Vol.10 (1), p.1944-1944, Article 1944
• Main Authors: Rajendran, Pradeep S., Challis, Rosemary C., Fowlkes, Charless C., Hanna, Peter, Tompkins, John D., Jordan, Maria C., Hiyari, Sarah, Gabris-Weber, Beth A., Greenbaum, Alon, Chan, Ken Y., Deverman, Benjamin E., Münzberg, Heike, Ardell, Jeffrey L., Salama, Guy, Gradinaru, Viviana, Shivkumar, Kalyanam
• Format: Article
• Language: English
• Subjects: 13/51; 14/19; 14/34; 14/35; 42/41; 42/44; 631/378/1959; 631/378/2632/1664; 631/378/3920; 64/110; 64/60; 9/25; Animals; Autonomic nervous system; Cholinergic Neurons - metabolism; Cholinergic Neurons - physiology; Cholinergics; Circuits; Electrical stimuli; Electrocardiography; Electrophysiology; Female; Ganglia; Heart rate; Heart Rate - physiology; Humanities and Social Sciences; Innervation; Male; Mice; Motor Neurons - physiology; multidisciplinary; Neural networks; Neurons; Norepinephrine; Organs; Parasympathetic nervous system; Peripheral Nervous System - metabolism; Peripheral Nervous System - physiology; Science; Science (multidisciplinary); Stellate ganglion; Sympathetic nervous system; Vagus nerve; Vagus Nerve - metabolism; Vagus Nerve - physiology; Wiring
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09770-1

Heart rate is under the precise control of the autonomic nervous system. However, the wiring of peripheral neural circuits that regulate heart rate is poorly understood. Here, we develop a clearing-imaging-analysis pipeline to visualize innervation of intact hearts in 3D and employed a multi-technique approach to map parasympathetic and sympathetic neural circuits that control heart rate in mice. We identify cholinergic neurons and noradrenergic neurons in an intrinsic cardiac ganglion and the stellate ganglia, respectively, that project to the sinoatrial node. We also report that the heart rate response to optogenetic versus electrical stimulation of the vagus nerve displays different temporal characteristics and that vagal afferents enhance parasympathetic and reduce sympathetic tone to the heart via central mechanisms. Our findings provide new insights into neural regulation of heart rate, and our methodology to study cardiac circuits can be readily used to interrogate neural control of other visceral organs. The wiring of peripheral neural circuits that regulate heart rate is poorly understood. In this study, authors used tissue clearing for high-resolution characterization of nerves in the heart in 3D and transgenic and novel viral vector approaches to identify peripheral parasympathetic and sympathetic neuronal populations involved in heart rate control in mice.