Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09770-1
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Funding
- NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) awards [OT2OD023848, OT2OD23864]
- NIH National Heart, Lung, and Blood Institute (NHLBI) grant [R01HL084261]
- NIH SPARC award [U01EB025138-01]
- NIH Director's New Innovator Award [DP2NS087949]
- NIH Presidential Early Career Award for Scientists and Engineers
- NIH National Institute on Aging grant [R01AG047664]
- NIH BRAIN Initiative award [U01NS090577]
- Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office
- National Science Foundation NeuroNex Technology Hub [1707316]
- Curci Foundation
- Beckman Institute
- Rosen Bioengineering Center at Caltech
- Heritage Medical Research Institute
- NIH NHLBI F31 Predoctoral Fellowship [F31HL127974]
- American Heart Association [17POST33410404]
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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.
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