Optogenetic vagotomy inhibits reflex bronchoconstriction and cardiac chronotropy

Abstract Optogenetics involves genetic insertion of light-sensitive ion channels into nerves, such as with cre-based recombination. The recent increase in cre-based mouse lines has expanded our ability to test the roles of peripheral nerves in homeostasis and in disease models. Here, we generated an optogenetic mouse line in which hyperpolarizing inhibitory halorhodopsin channels were inserted into vagal cholinergic (parasympathetic) nerves using choline acetyltransferase (ChAT)-cre, enabling targeted inhibition of parasympathetic nerves. Halorhodopsin expression in parasympathetic neurons was confirmed by RT-PCR and confocal microscopy. Nerve reflex responses were generated with aerosolized serotonin or methacholine, during which mice were exposed to hyperpolarizing 645 nm or control 454 nm and 570 nm light. Inhibition of parasympathetic nerves by halorhodopsin attenuated airway hyperreactivity in house dust mite challenged mice while inhibition of cardiac cholinergic nerves increased heart rate. Our findings demonstrate the utility of halorhodopsin as a tool for testing the roles of parasympathetic nerves in cardiopulmonary function.