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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Meng Liu
- Meng Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Yang Dan, University of California, Berkeley, United States
© 2019, Sun et al.
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.
An animal entering a new environment typically faces three challenges: explore the space for resources, memorize their locations, and navigate towards those targets as needed. Here we propose a neural algorithm that can solve all these problems and operates reliably in diverse and complex environments. At its core, the mechanism makes use of a behavioral module common to all motile animals, namely the ability to follow an odor to its source. We show how the brain can learn to generate internal “virtual odors” that guide the animal to any location of interest. This endotaxis algorithm can be implemented with a simple 3-layer neural circuit using only biologically realistic structures and learning rules. Several neural components of this scheme are found in brains from insects to humans. Nature may have evolved a general mechanism for search and navigation on the ancient backbone of chemotaxis.