Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

Hanna Hayat, Noa Regev, Noa Matosevich, Anna C Sales, Elena Paredes, Aaron Krom, Lottem Bergman, Yong Li, Marina Lavigne, Eric J Kremer, Ofer Yizhar, Anthony E Pickering, Yuval Nir*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

109 Citations (Scopus)
145 Downloads (Pure)


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.
Original languageEnglish
Article numbereaaz4232
JournalScience Advances
Issue number15
Publication statusPublished - 8 Apr 2020

Structured keywords

  • Anaesthesia Pain and Critical Care


  • Auditory
  • LC
  • noradrenaline
  • arousal threshold
  • NREM
  • REM
  • optogenetics


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