Amygdala GABAergic neuron activity dynamic during cataplexy of narcolepsy

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Abstract

Recent studies showed activation of the GABAergic neurons in the central nucleus of the amygdala (CeA) triggered cataplexy of sleep disorder narcolepsy. However, there is still no direct evidence on CeA GABAergic neurons' real-time dynamic during cataplexy. We used a deep brain calcium imaging tool to image the intrinsic calcium transient as a marker of neuronal activity changes in the narcoleptic VGAT-Cre mice by expressing the calcium sensor GCaMP6 into genetically defined CeA GABAergic neurons. Two distinct GABAergic neuronal groups involved in cataplexy were identified: spontaneous cataplexy-ON and predator odor-induced cataplexy-ON neurons. Majority in the latter group were inactive during regular sleep/wake cycles but were specifically activated by predator odor and continued their intense activities into succeeding cataplexy bouts. Furthermore, we found that CeA GABAergic neurons became highly synchronized during predator odor-induced cataplexy. We suggest that the abnormal activation and synchronization of CeA GABAergic neurons may trigger emotion-induced cataplexy.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Ying Sun

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States

Competing interests
The authors declare that no competing interests exist.
Emmaline Bendell

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States

Competing interests
The authors declare that no competing interests exist.
Meng Liu

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States

For correspondence
liumen@musc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1394-5014

Funding

National Institute of Neurological Disorders and Stroke (1R01NS096151)

Meng Liu

National Institute of Neurological Disorders and Stroke (1R21NS101469)

Meng Liu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All manipulations done to the mice followed the policies established in the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Medical University of South Carolina Institutional Animal Care and Use Committee (protocol # IACUC-2019-00723). All surgery was performed under isoflurane inhalation, and every effort was made to minimize suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.