Activity dynamics of amygdala GABAergic neurons during cataplexy of narcolepsy.

Ying Sun,Meng Liu,Siwei Luo,Carlos Blanco-Centurion,Emmaline Bendell,Aurelio Vidal-Ortiz

doi:10.7554/elife.48311

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.

Highlights

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep fragmentation, and hypnogogic/hypnopompic hallucinations
GCaMP6s predominantly expressed within the central nucleus of the amygdala (CeA) area (>80%), but some scattered expression was observed within the basolateral amygdala (BLA) and the basomedial amygdala (BMA) (Figure 1D)
We found that in both control and narcoleptic mice, CeA GABAergic neurons showed their maximal activities during active waking (AW) and rapid eye movement sleep (REMS)

Summary

Introduction

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep fragmentation, and hypnogogic/hypnopompic hallucinations. Even though it is known that the loss of the neuropeptide orexin (hypocretin, HCRT) system causes narcolepsy with cataplexy (Lin et al, 1999; Nishino et al, 2000a), the entire brain circuitry responsible for the presentation of all narcoleptic symptoms is not fully understood. The intrinsic technical limitations of the singleunit recordings prevented the identification of the phenotypes of those neurons activated during cataplexy. To overcome this limitation, in the present study, we took advantage of molecular genetic tools to both tag and measure the in vivo activity of CeA GABAergic neurons from transgenic narcoleptic mice.

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Discussion

Conclusion