Abstract
A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus-coeruleus norepinephrine (LC-NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction of NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Importantly, minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced
the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.
the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.
Original language | English |
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Article number | eaaz4232 |
Journal | Science Advances |
Volume | 6 |
Issue number | 15 |
DOIs | |
Publication status | Published - 8 Apr 2020 |
Research Groups and Themes
- Anaesthesia Pain and Critical Care
Keywords
- Auditory
- LC
- noradrenaline
- arousal threshold
- NREM
- REM
- optogenetics
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Dive into the research topics of 'Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep'. Together they form a unique fingerprint.Student theses
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Theoretical, electrophysiological and optogenetic interrogation of Locus Coeruleus contributions to cognition
Sales, A. C. (Author), Pickering, A. E. (Supervisor), Jones, M. W. (Supervisor) & Moran, R. J. (Supervisor), 24 Mar 2020Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)
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Profiles
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Professor Anthony Edward Pickering
- School of Physiology, Pharmacology & Neuroscience - Professor of Neuroscience and Anaesthesia
- Bristol Neuroscience
Person: Academic , Member