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Updated: May 7, 2026
Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity
Published on: March 5, 2020
Optogenetic vagotomy inhibits reflex bronchoconstriction and cardiac chronotropy
Aubrey B Pierce1, Alexandra B Pincus2, James Kornfield1
1Division of Pulmonary, Allergy, and Critical Care Medicine, Oregon Health & Science University.
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.
Insights
Optogenetics using halorhodopsin in vagal nerves can inhibit parasympathetic activity. This approach successfully reduced airway hyperreactivity and altered heart rate, demonstrating its utility in studying cardiopulmonary function.
Area of Science:
- Neuroscience
- Physiology
- Genetics
Background:
- Optogenetics enables targeted control of neural activity.
- Cre-based mouse lines facilitate studying peripheral nerve roles.
- Parasympathetic nerves significantly influence homeostasis and disease.
Purpose of the Study:
- To develop a novel optogenetic tool for inhibiting vagal parasympathetic nerves.
- To investigate the role of parasympathetic nerves in airway hyperreactivity and cardiac function.
Main Methods:
- Generated a Choline acetyltransferase (ChAT)-cre mouse line for targeting parasympathetic neurons.
- Expressed inhibitory halorhodopsin channels in vagal cholinergic nerves.
- Utilized light stimulation (645 nm) to inhibit nerve activity and assessed responses.
Main Results:
- Confirmed halorhodopsin expression in parasympathetic neurons via RT-PCR and microscopy.
- Inhibition of parasympathetic nerves attenuated airway hyperreactivity in house dust mite challenged mice.
- Inhibition of cardiac cholinergic nerves led to an increased heart rate.
Conclusions:
- Halorhodopsin is an effective tool for inhibiting parasympathetic nerve activity.
- This optogenetic strategy aids in dissecting the role of parasympathetic nerves in cardiopulmonary regulation.
- The developed mouse line offers new possibilities for research in autonomic nervous system disorders.
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