Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery

Trends in Pharmacological Sciences, Journal Year: 2019, Volume and Issue: 40(7), P. 464 - 481

Published: May 27, 2019

Language: Английский

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Hypothalamic Circuits for Predation and Evasion

Neuron, Journal Year: 2018, Volume and Issue: 97(4), P. 911 - 924.e5

Published: Feb. 1, 2018

Language: Английский

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Arousal and sleep circuits

Neuropsychopharmacology, Journal Year: 2019, Volume and Issue: 45(1), P. 6 - 20

Published: June 19, 2019

Language: Английский

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Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

Science Advances, Journal Year: 2020, Volume and Issue: 6(15)

Published: April 8, 2020

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that locus coeruleus (LC) norepinephrine (NE) activity during mediates unresponsiveness, and its action promotes awakenings. tested this using electrophysiological, behavioral, pharmacological, optogenetic techniques alongside auditory stimulation in freely behaving rats. found systemic reduction NE signaling lowered probability sound-evoked awakenings (SEAs). The level tonic LC anticipated SEAs. Optogenetic activation promoted as evident sleep-wake transitions, EEG desynchronization, pupil dilation. Minimal excitation before sound presentation increased SEA probability. silencing a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed spiking constricted pupils. Brief periods opto-silencing Thus, LC-NE determines likelihood awakenings, constitutes key factor behavioral unresponsiveness.

Language: Английский

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Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Sept. 25, 2017

Abstract Sleep control is ascribed to a two-process model, widely accepted concept that posits homoeostatic drive and circadian process as the major sleep-regulating factors. Cognitive emotional factors also influence sleep–wake behaviour; however, precise circuit mechanisms underlying their effects on sleep are unknown. Previous studies suggest adenosine has role affecting behavioural arousal in nucleus accumbens (NAc), brain area critical for reinforcement reward. Here, we show chemogenetic or optogenetic activation of excitatory A 2A receptor-expressing indirect pathway neurons core region NAc strongly induces slow-wave sleep. Chemogenetic inhibition prevents induction, but does not affect rebound. In addition, motivational stimuli inhibit activity ventral pallidum-projecting suppress Our findings reveal prominent contribution this associated with motivation.

Language: Английский

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VTA GABA Neurons at the Interface of Stress and Reward

Frontiers in Neural Circuits, Journal Year: 2019, Volume and Issue: 13

Published: Dec. 5, 2019

The ventral tegmental area (VTA) is best known for its robust dopaminergic projections to forebrain regions and their critical role in regulating reward, motivation, cognition, aversion. However, the VTA not only made of dopamine (DA) cells, as approximately 35% cells are GABA neurons. These neurons play a dual role, provide both local inhibition DA long-range several distal brain regions. have increasingly been recognized potent mediators reward aversion own right, well potential targets treatment addiction, depression, other stress-linked disorders. In this review, we dissect circuit architecture, physiology, behavioral roles suggest gaps be addressed.

Language: Английский

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Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice

Journal of Neuroscience, Journal Year: 2016, Volume and Issue: 37(5), P. 1352 - 1366

Published: Dec. 30, 2016

The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation PPT region during sleep leads to awakening, whereas lesions cats reduce REM Though these effects have linked with cholinergic neurons, also includes intermingled glutamatergic GABAergic cell populations, precise roles cholinergic, glutamatergic, groups regulating state remain unknown. Using a chemogenetic approach three Cre-driver mouse lines, we found that selective activation neurons induced prolonged wakefulness, inhibition reduced wakefulness increased non-REM (NREM) Activation suppressed lower-frequency electroencephalogram rhythms NREM Last, slightly These findings reveal differentially influence sleep/wake states. SIGNIFICANCE STATEMENT More than 40 million Americans suffer from chronic disruption, development effective treatments requires more detailed understanding neuronal mechanisms controlling arousal. considered key site for This is mainly because contained nucleus. However, contains likely contribute sleep–wake experiments present study each distinct on behavior, improving our how regulates

Language: Английский

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Dopamine and Noradrenaline in the Brain; Overlapping or Dissociate Functions?

Frontiers in Molecular Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: Jan. 21, 2020

Dopamine and noradrenaline are crucial neuromodulators controlling brain states, vigilance, action, reward, learning, memory processes. Ventral tegmental area (VTA) Locus Coeruleus (LC) canonically described as the main sources of dopamine (DA) (NA) with dissociate functions. A comparison diverse studies shows that these largely overlap in multiple domains such shared biosynthetic pathway co-release from LC terminals, convergent innervations, non-specificity receptors transporters, intracellular signaling pathways. DA-NA interactions mainly studied prefrontal cortex hippocampus, yet it can be extended to whole given diversity catecholamine innervations. simultaneously broadcast both across brain. Here, we briefly review molecular, cellular, physiological overlaps between DA NA systems point their functional implications. We suggest may function parallel facilitate learning maintain states required for normal cognitive Various modules have been targeted developing therapeutics. Understanding two is more effective interventions a range neuropsychiatric conditions.

Language: Английский

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The Temperature Dependence of Sleep

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: April 24, 2019

Mammals have evolved a range of behavioural and neurological mechanisms that coordinate cycles thermoregulation sleep. Whether diurnal or nocturnal, sleep onset reduction in core temperature occur together. Non-rapid eye movement (NREM) episodes are also accompanied by brain cooling. Thermoregulatory behaviours, like nest building curling up, accompany this circadian decline preparation for sleeping. This could be matter simply comfort as animals seek warmth to compensate lower temperatures. However, both humans other mammals, direct skin warming can shorten sleep-latency promote NREM We discuss the evidence body cooling more fundamentally connected thermoregulatory prior sleep, form warm microclimates accelerate directly through neuronal circuits. Paradoxically, might induce vasodilation In way, seeking nesting behaviour enhance cycle activating specific circuits link initiation suggest these explain why is most likely when at its steepest rate transitions decrease temperature. connection may implications energy homeostasis function

Language: Английский

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A Motor Theory of Sleep-Wake Control: Arousal-Action Circuit

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 27 - 46

Published: Jan. 30, 2019

Wakefulness, rapid eye movement (REM) sleep, and non-rapid (NREM) sleep are characterized by distinct electroencephalogram (EEG), electromyogram (EMG), autonomic profiles. The circuit mechanism coordinating these changes during sleep-wake transitions remains poorly understood. past few years have witnessed progress in the identification of REM NREM neurons, which constitute highly distributed networks spanning forebrain, midbrain, hindbrain. Here we propose an arousal-action for control wakefulness is supported separate arousal action while neurons part central somatic motor circuits. This model well currently known wake neurons. It can also account EEG, EMG, profiles wake, REM, states several key features their transitions. intimate association between autonomic/somatic circuits suggests that a primary function to suppress activity.

Language: Английский

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