Memory-enhancing properties of sleep depend on the oscillatory amplitude of norepinephrine

Abstract

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 Ca 2+ to norepinephrine is reduced during sleep

Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease

“…Noradrenaline plays a key role in modulating selective attention 71 and with serotonin, modulates behavioural responses to incoming visual information 61 . The noradrenergic system is also likely to play a key role in mediating functional state transitions: noradrenaline-mediated apical amplification of pyramidal cells differentiates waking and anaesthesia 72 , extracellular noradrenaline is associated with sleep-state transitions 73 and locus coeruleus activity flexibly mediates the recruitment of other neural circuits particularly the prefrontal cortex 74 , leading to dynamic changes in functional networks, specifically transitioning between motor and tasknegative networks 75 . Changes within the noradrenergic system may be involved in altered state transitions in PDhallucinations by modulating the activity of sensory cortices and thalamocortical neurocircuitry 76 .…”

Noradrenergic cross-modular reciprocal inhibition within the locus coeruleus

“…Such infra-slow LC oscillations have recently been linked to the microarchitecture of non-REM sleep with a periodicity of around 50-70s (Matosevich & Nir, 2021;Osorio-Forero et al, 2021;Kjaerby et al, 2022;Morici & Girardeau, 2022) and the causal involvement of LC-prefrontal and LC-thalamic projections which operate in synchrony.…”

“…This activity oscillation had a relatively slow time-course (frequency ∼0.007 Hz) and this may be related to the infra-slow oscillation that has previously been observed in the LC in vivo (Totah et al ., 2018). Such infra-slow LC oscillations have recently been linked to the microarchitecture of non-REM sleep with a periodicity of around 50-70s (Matosevich & Nir, 2021; Osorio-Forero et al ., 2021; Kjaerby et al ., 2022; Morici & Girardeau, 2022) and the causal involvement of LC-prefrontal and LC-thalamic projections which operate in synchrony. It may be that the opponency between these two and the remaining LC modules may account for these oscillations.…”

“…LC neurons extend remarkable axonal projection trees to much of the brain to release noradrenaline. In behaving animals, the LC neurons display tonic ‘pacemaker’ firing at rates of ∼0.5-5Hz, with the rate of this tonic activity broadly correlating with levels of alertness (Aston-Jones & Bloom, 1981; Aston-Jones & Cohen, 2005) and this activity ceases during rapid eye movement (REM) sleep (Hayat et al ., 2020; Kjaerby et al ., 2022). In addition to ongoing tonic activity, LC neurons also display a burst-firing mode of activity, known as phasic, in response to novel or emotionally salient stimuli.…”

Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport

“…Second, how sleep cycle-dependent vascular dynamics are regulated. For instance, one potential effector for vascular dynamics could be fluctuations in norepinephrine levels across the sleep cycle 17 and its interplay with astrocytic endfeet, that were recently shown to generate ultra-slow arteriole oscillations in awake mice 18 . Third, how vascular dynamics affect intraparenchymal waste clearance.…”