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The ability to forget fear-inducing situations is essential for adapting to our environment, but the neural mechanisms underlying 'fear forgetting' remain unclear. Novel findings reveal that the activity of the infralimbic cortex - specifically during REM sleep - contributes to the extinction of fear memory., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Stress disrupts sleep, but the neural mechanisms underlying this relationship remain unclear. Novel findings in mice reveal a hypothalamic circuit that fragments sleep and promotes arousal after stress., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Waking behaviors such as sitting or standing require suitable levels of muscle tone. But it is unclear how arousal and motor circuits communicate with one another so that appropriate motor tone occurs during wakefulness. Cataplexy is a peculiar condition in which muscle tone is involuntarily lost during normal periods of wakefulness. Cataplexy therefore provides a unique opportunity for identifying the signaling mechanisms that synchronize motor and arousal behaviors. Cataplexy occurs when hypothalamic orexin neurons are lost in narcolepsy; however, it is unclear if motor-arousal decoupling in cataplexy is directly or indirectly caused by orexin cell loss. Here, we used genomic, proteomic, chemogenetic, electrophysiological, and behavioral assays to determine if grafting orexin cells into the brain of cataplectic (i.e., orexin -/- ) mice restores normal motor-arousal behaviors by preventing cataplexy. First, we engineered immortalized orexin cells and found that they not only produce and release orexin but also exhibit a gene profile that mimics native orexin neurons. Second, we show that engineered orexin cells thrive and integrate into host tissue when transplanted into the brain of mice. Next, we found that grafting only 200-300 orexin cells into the dorsal raphe nucleus-a region densely innervated by native orexin neurons-reduces cataplexy. Last, we show that real-time chemogenetic activation of orexin cells restores motor-arousal synchrony by preventing cataplexy. We suggest that orexin signaling is critical for arousal-motor synchrony during wakefulness and that the dorsal raphe plays a pivotal role in coupling arousal and motor behaviors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite intensive research efforts, biologists still do not have a clear picture of the brain circuitry that controls behavioural arousal. However, new research has identified a novel septo-hypothalamic circuit that functions to promote wakefulness., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Interview with John Peever, who studies the brain mechanisms that control REM sleep and how their dysfunction underlies sleep disorders at the University of Toronto., (Copyright © 2020.)

Dangerous or alerting stimuli typically trigger arousal from sleep; however, the brain circuitry responsible for threat detection during sleep remains unclear. New research in mice identified a specific class of neuron in the basal forebrain that causes arousal from sleep by responding to threatening stimuli., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Appropriate levels of muscle tone are needed to support waking behaviors such as sitting or standing. However, it is unclear how the brain functions to couple muscle tone with waking behaviors. Cataplexy is a unique experiment of nature in which muscle paralysis involuntarily intrudes into otherwise normal periods of wakefulness. Cataplexy therefore provides the opportunity to identify the circuit mechanisms that couple muscle tone and waking behaviors. Here, we tested the long-standing hypothesis that muscle paralysis during cataplexy is caused by recruitment of the brainstem circuit that induces muscle paralysis during REM sleep. Using behavioral, electrophysiological, and chemogenetic strategies, we found that muscle tone and arousal state can be decoupled by manipulation of the REM sleep circuit (the sublaterodorsal tegmental nucleus [SLD]). First, we show that silencing SLD neurons prevents motor suppression during REM sleep. Second, we show that activating these same neurons promotes cataplexy in narcoleptic (orexin -/- ) mice, whereas silencing these neurons prevents cataplexy. Most importantly, we show that SLD neurons can decouple motor activity and arousal state in healthy mice. We show that SLD activation triggers cataplexy-like attacks in wild-type mice that are behaviorally and electrophysiologically indistinguishable from cataplexy in orexin -/- mice. We conclude that the SLD functions to engage arousal-motor synchrony during both wakefulness and REM sleep, and we propose that pathological recruitment of SLD neurons could underlie cataplexy in narcolepsy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Skin and body warming help initiate sleep, but the underlying neural mechanisms remain unclear. New research in mice shows that skin warming recruits a previously unidentified hypothalamic circuit that functions to promote sleep and body cooling., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

During REM sleep, skeletal muscles are paralyzed in one moment but twitch and jerk in the next. REM sleep twitches are traditionally considered random motor events that result from momentary lapses in REM sleep paralysis [1-3]. However, recent evidence indicates that twitches are not byproducts of REM sleep, but are in fact self-generated events that could function to promote motor learning and development [4-6]. If REM twitches are indeed purposefully generated, then they should be controlled by a coordinated and definable mechanism. Here, we used behavioral, electrophysiological, pharmacological, and neuroanatomical methods to demonstrate that an inhibitory drive onto skeletal motoneurons produces a temporally coordinated pattern of muscle twitches during REM sleep. First, we show that muscle twitches in adult rats are not uniformly distributed during REM sleep, but instead follow a well-defined temporal trajectory. They are largely absent during REM initiation but increase steadily thereafter, peaking toward REM termination. Next, we identify the transmitter mechanism that controls the temporal nature of twitch activity. Specifically, we show that a GABA and glycine drive onto motoneurons prevents twitch activity during REM initiation, but progressive weakening of this drive functions to promote twitch activity during REM termination. These results demonstrate that REM twitches are not random byproducts of REM sleep, but are instead rather coherently generated events controlled by a temporally variable inhibitory drive., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

How does the brain control dreams? New science shows that a small node of cells in the medulla - the most primitive part of the brain - may function to control REM sleep, the brain state that underlies dreaming., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

How much would we sleep if we lived without the pressures and distractions associated with industrialized lifestyles? New research shows that hunter-gatherer societies sleep for 6-7 hours a night--a level similar to industrialized societies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

During rapid eye movement sleep, the forelimb muscles of newborn rats jerk and twitch in an organized pattern, the fidelity of which improves with time. The coordinated nature of such sleep movements may instruct the developing brain how to more effectively execute movements during wakefulness., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Appropriate levels of skeletal muscle tone are needed to support routine motor behaviors. But, the brain mechanisms that function to couple muscle tone with waking behaviors are unknown. We addressed this question by studying mice with cataplexy--a condition caused by a decoupling of motor and arousal behaviors. Cataplexy is characterized by involuntary loss of muscle tone during wakefulness, which results in postural collapse during otherwise normal consciousness. Cataplexy is caused by loss of hypocretin (orexin) cells, but it is unknown how this loss triggers motor inactivity during cataplexy. Here, we used hypocretin knockout mice to identify the neurochemical cause of cataplexy and to determine the biochemical mechanisms that normally function to couple arousal and motor systems., Results: Using genetic, behavioral, electrophysiological, and pharmacological approaches, we show that the noradrenergic system acts to synchronize motor and arousal systems. Specifically, we show that an excitatory noradrenergic drive maintains postural muscle tone during wakefulness by activating α1 receptors on skeletal motoneurons. Loss of this normal excitatory drive triggers motor inactivity during cataplexy by reducing motoneuron excitation. However, loss of this drive does not affect arousal since mice remain awake during cataplexy, suggesting the noradrenergic system is not required for maintaining wakefulness. Artificial restoration of noradrenergic drive to motoneurons prevents motor inactivity and rescues cataplexy., Conclusions: We conclude that hypocretin deficiency causes cataplexy by short-circuiting the noradrenergic drive to skeletal motoneurons. We suggest that the noradrenergic system functions to couple the brain systems that control postural muscle tone and behavioral arousal state., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The barrel cortex and whisker thalamus preferentially respond to whisker movements during REM sleep in infant rats. Understanding why the brain tunes into sensory signals while it's tuned out in sleep may provide clues about the functions of REM sleep., (Copyright © 2012 Elsevier Ltd. All rights reserved.)