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Publication : Optogenetic Control of Airway Cholinergic Neurons In Vivo.

First Author  Pincus AB Year  2020
Journal  Am J Respir Cell Mol Biol Volume  62
Issue  4 Pages  423-429
PubMed ID  31899655 Mgi Jnum  J:365870
Mgi Id  MGI:6690786 Doi  10.1165/rcmb.2019-0378MA
Citation  Pincus AB, et al. (2020) Optogenetic Control of Airway Cholinergic Neurons In Vivo. Am J Respir Cell Mol Biol 62(4):423-429
abstractText  Dysregulation of airway nerves leads to airway hyperreactivity, a hallmark of asthma. Although changes to nerve density and phenotype have been described in asthma, the relevance of these changes to nerve function has not been investigated due to anatomical limitations where afferent and efferent nerves run in the same nerve trunk, making it difficult to assess their independent contributions. We developed a unique and accessible system to activate specific airway nerves to investigate their function in mouse models of airway disease. We describe a method to specifically activate cholinergic neurons using light, resulting in immediate, measurable increases in airway inflation pressure and decreases in heart rate. Expression of light-activated channelrhodopsin 2 in these neurons is governed by Cre expression under the endogenous choline acetyltransferase promoter, and we describe a method to decrease variability in channelrhodopsin expression in future experiments. Optogenetic activation of specific subsets of airway neurons will be useful for studying the functional relevance of other observed changes, such as changes to nerve morphology and protein expression, across many airway diseases, and may be used to study the function of subpopulations of autonomic neurons in lungs and other organs.
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