# Mechanisms of Cataplexy

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $382,813

## Abstract

Muscle paralysis is a normal aspect of REM sleep, but dysfunction in the paralysis system gives rise to
cataplexy, sudden episodes of paralysis in people with narcolepsy. Just the opposite occurs in REM sleep
behavior disorder (RBD) in which people act out their dreams, often resulting in injury. With both cataplexy and
RBD, the events are frequently brought on by strong emotions: cataplexy is often triggered when laughing at a
joke with friends, and people with RBD often lash out when dreaming about fighting a foe. To develop better
therapies for these disorders, it is essential to understand how the brain circuitry that underlies emotions
regulates muscle tone.
 Cataplexy is mainly triggered by strong positive emotions, usually when socially interacting with close
friends and family. The amygdala mediates behavioral responses to emotions, and prior research plus our pilot
data suggest that cataplexy is triggered by neurons in the central nucleus of the amygdala that express the
oxytocin receptor (CeAOTR). Specifically, with positive emotions, CeAOTR neurons may promote cataplexy by
activating brainstem pathways that regulate the paralysis of REM sleep.
 Our long-term objectives are to determine the role of the CeAOTR neurons in regulating cataplexy, to
define the brainstem mechanisms through which they trigger paralysis, and to identify the upstream signals
through which they are activated. First, we will determine whether the CeAOTR neurons promote cataplexy by
activating and inhibiting these neurons using chemogenetics. We will then record the activity of these neurons
across cataplexy and sleep states using calcium imaging in freely moving mice. Next, we will define the neural
targets through which the CeAOTR neurons promote cataplexy by mapping their connections to brainstem
circuits that regulate muscle tone. We will establish if these neural pathways activate or inhibit these brainstem
regions using brain slice recordings, and we will test the necessity of these projections using optogenetic
activation or inhibition. Last, we will define the neural inputs to the CeAOTR neurons that promote cataplexy
using conditional and conventional pathway tracing, and we will test if rewarding social interaction triggers
cataplexy and whether this is mediated by oxytocin.
 Collectively, these multidisciplinary experiments will define the neural mechanisms through which
positive emotions including social signals activate amygdala neurons and brainstem paralysis mechanisms. An
improved understanding of how emotions regulate muscle tone should shed light on the normal regulation of
muscle paralysis during REM sleep, and ultimately lead to better treatments for narcolepsy, RBD, and other
disorders of muscle tone.

## Key facts

- **NIH application ID:** 10133752
- **Project number:** 5R01NS106032-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** THOMAS E SCAMMELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,813
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133752

## Citation

> US National Institutes of Health, RePORTER application 10133752, Mechanisms of Cataplexy (5R01NS106032-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133752. Licensed CC0.

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