Optogenetic Control of Cardiac Autonomic Neurons in Transgenic Mice

Optogenetic technology has enabled unparalleled insights into cellular and organ physiology by providing exquisite temporal and spatial control of biological pathways. Here, an optogenetic approach is presented for selective activation of the intrinsic cardiac nervous system in excised perfused mouse hearts. The breeding of transgenic mice that have selective expression of channelrhodopsin in either catecholaminergic or cholinergic neurons is described. An approach for perfusing hearts excised from those animals, recording the ECG to measure heart rate changes, and an illumination technique using a custom micro-LED light source to activate channelrhodopsin is explained. We have used these methods in ongoing studies of the kinetics of autonomic control of cardiac electrophysiology and contractility, demonstrating the proven utility of optogenetic technology to enable unparalleled spatiotemporal anatomic-functional probing of the intrinsic cardiac nervous system.