Narcolepsy is a disorder of unstable wake and sleep states caused by the lack of orexin neurons which degenerate most likely as a consequence of an autoimmune process. The state instability of narcolepsy includes rapid eye movement (REM) sleep intruding into wake in the form of dream-like hallucinations and cataplexy, muscle paralysis (atonia) much like occurs in REM sleep. In mice lacking orexin peptides, cataplexy is also observed with similar presentation as in humans of muscle paralysis during wakefulness which is often triggered by positive emotions. Prior research showed that the activation of the central amygdala is sufficient to promote cataplexy in a mouse model of narcolepsy. The central amygdala (CeA) contains a variety of neuronal types, and we hypothesize that γ-aminobutyric acid (GABA)-ergic neurons expressing the oxytocin receptor (OTR) mediate cataplexy as these neurons project to a known REM sleep atonia-regulating region, the ventrolateral periaqueductal gray (vlPAG)/lateral pontine tegmentum (LPT), and, as oxytocin (OT) sensitive neurons in the amygdala, likely participate in emotional processing and social behavior. In this study, we used fiber photometry to investigate the behavior of these neurons in response to social and rewarding stimuli, during emotion-triggered cataplexy, and across arousal states in an effort to define their potential role in emotion-triggered cataplexy. Initial recordings were conducted at too low an excitation light power to stimulate the green fluorescent calcium indicator, GCaMP6s, but were useful in optimizing MATLAB analysis and behavioral tests later done at higher LED power. The second series of recordings with higher excitation light power and better signal to noise ratio, showed increased activity in response to social interaction and reward, prior to REM transitions, and decreased activity during cataplexy confirming patterns seen in initial recordings. In recordings with higher excitation light, these responses appear to occur before interaction with stimulus mice or reward stimulus. In the future, additional recordings with a higher signal to noise ratio will be needed to confirm these results. In conclusion, responses of CeA-OTR neurons to social and rewarding stimuli, cataplexy, and at REM transitions are in support of a possible role of these neurons in emotion-triggered cataplexy which can be tested using additional methods, such as optogenetics.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36300 |
| Date | 11 June 2019 |
| Creators | Begovic, Jelena |
| Contributors | Franzblau, Carl, Scammell, Thomas E. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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