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Functional Response of Perfused Hearts to Optogenetic Activation of Cholinrgic Neurons Open Access

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Parasympathetic cholinergic neurons produce acetylcholine and are found in the central and peripheral nervous system. The structure and function of parasympathetic cholinergic neurons that innervate the heart remains incompletely understood. It was hypothesized that cardiac cholinergic neurons have a significant influence on ventricular function by reducing heart rate (HR) and increasing coronary vasodilation, measured by increased coronary flow rate (CFR). The response of optogenetic activation of cholinergic neurons in the right atrium was studied using Langendorff perfused mice hearts followed by periods of optical stimulation. Hearts were also cleared with CUBIC to further study the structure of cardiac cholinergic neurons. Results of a paired t-test indicated significant drops in HR when cholinergic neurons were activated, as hypothesized. Significant drops in CFR during stimulation were observed, contrary to our hypothesis. However, HR was a confounding variable in the experiments, which may have contributed to reductions in CFR. Next steps include isolating CFR measurements from HR influence to determine if, independently, CFR increases in the presence of exogenous acetylcholine. This correlation should provide more evidence for cholinergic neurons as the mechanism for parasympathetic control on the heart, leading to a decreased HR and changes in CFR. A better understanding of the anatomy of cholinergic neurons and their functionality will provide an overall better understanding of the human heart and its abnormalities, thereby also improving targets for disease treatment.

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