Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep
| Autor: | Ofer Yizhar, Lottem Bergman, Noa Regev, Aaron J Krom, Noa Matosevich, Yuval Nir, Anna C Sales, Marina Lavigne, Eric J. Kremer, Elena Paredes-Rodriguez, Anthony E. Pickering, Yong Li, Hanna Hayat |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
medicine.diagnostic_test business.industry Sensory system Gating Optogenetics Electroencephalography Arousal 03 medical and health sciences Electrophysiology 0302 clinical medicine Pupillary response Medicine Locus coeruleus business Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/539502 |
| Popis: | A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms gating 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, liminal 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. |
| Databáze: | OpenAIRE |
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