Summary
We normally regard sleep and wake as two distinct opposing brain states, where sleep requires silence of wake-promoting structures such as the locus coeruleus (LC)-norepinephrine (NE) system. We set out to investigate how cortical NE dynamics and NE-related astrocytic activity relates to LC population activity during sleep states.
We show that LC displays regular phasic activity bouts during NREM sleep leading to a slow oscillatory pattern of prefrontal NE levels of which the majority of NE increases does not lead to awakening. NE troughs link to sleep spindles and continued NE decline transitions into REM sleep. Last, we show that prefrontal astrocytes have reduced sensitivity towards NE during sleep.
Our results suggest that dynamic changes in the activity of wake-promoting systems during sleep create alternation between crucial sleep processes and broadening of sensitivity towards incoming sensory input.
Highlights
Extracellular levels of norepinephrine display dynamic changes during NREM and REM sleep
Phasic activity of locus coeruleus neurons during NREM underlies slow norepinephrine oscillations
Spindles occur at norepinephrine troughs and are abolished by norepinephrine increases
Increased spindles prior to REM reflect the beginning of a long-lasting norepinephrine decline
REM episodes are characterized by a sub-threshold continuous norepinephrine decline
The responsiveness of astrocytic Ca2+ to norepinephrine is reduced during sleep
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Lead Contact: Maiken Nedergaard (nedergaard{at}sund.ku.dk)
Further information should be directed to and will be fulfilled by the Lead Contact, Maiken Nedergaard (nedergaard{at}sund.ku.dk).
