Sleep is an active state critical for processing emotional memories encoded during waking in both humans and animals. There is a remarkable overlap between the brain structures and circuits active during sleep, particularly rapid eye-movement (REM) sleep, and the those encoding emotions. Accordingly, disruptions in sleep quality or quantity, including REM sleep, are often associated with, and precede the onset of, nearly all affective psychiatric and mood disorders. In this context, a major biomedical challenge is to better understand the underlying mechanisms of the relationship between (REM) sleep and emotion encoding to improve treatments for mental health. This lecture will summarize our investigation of the cellular and circuit mechanisms underlying sleep architecture, sleep oscillations, and local brain dynamics across sleep-wake states using electrophysiological recordings combined with single-cell calcium imaging or optogenetics. The presentation will detail the discovery of a 'somato-dendritic decoupling'in prefrontal cortex pyramidal neurons underlying REM sleep-dependent stabilization of optimal emotional memory traces. This decoupling reflects a tonic inhibition at the somas of pyramidal cells, occurring simultaneously with a selective disinhibition of their dendritic arbors selectively during REM sleep. Recent findings on REM sleep-dependent subcortical inputs and neuromodulation of this decoupling will be discussed in the context of synaptic plasticity and the optimization of emotional responses in the maintenance of mental health.

Alterations in sleep are hallmarks of the ageing process and emerges as risk factors for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD-related processes is not fully established. We investigated whether sleep arousals and the coupling of spindles and slow waves, key elements of sleep microstructure, are associated with early amyloid-beta (Aβ) brain burden, hallmark of AD neuropathology, and cognitive change at 2 years in 100 late-midlife healthy individuals. We first found that arousals interrupting sleep continuity were positively linked to Aβ burden, while, by contrast, the more prevalent arousals upholding sleep continuity were associated with lower Aβ burden and better cognition. We further found that young-like co-occurrence of spindles and slow-depolarisation slow waves is associated to lower burden of Aβ over the medial prefrontal cortex and is predictive of memory decline at 2-year follow-up. We provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. We further show the altered coupling of sleep microstructure elements that are key to its mnesic functions may contribute to poorer brain and cognitive trajectories. The presentation will end with preliminary data show that activity of the locus coeruleus, essential to sleep and showing some of the earliest signs of AD-related pathological processes, is associated with sleep quality. These preliminary findings are the first of a project ailed at link sleep and AD through the locus coeruleus.

Daily caffeine consumption and chronic sleep restriction are highly prevalent in society. It is well established that acute caffeine intake under controlled conditions enhances vigilance and promotes wakefulness but can also delay sleep initiation and reduce electroencephalographic (EEG) markers of sleep intensity, particularly in susceptible individuals. To investigate whether these effects are also present during chronic consumption of coffee/caffeine, we recently conducted several complementary studies. We examined whether repeated coffee intake in dose and timing mimicking ‘real world’ habits maintains simple and complex attentional processes during chronic sleep restriction, such as during a busy work week. We found in genetically caffeine-sensitive individuals that regular coffee (300 mg caffeine/day) benefits most attentional tasks for 3-4 days when compared to decaffeinated coffee. Genetic variants were also used in the population-based HypnoLaus cohort, to investigate whether habitual caffeine consumption causally affects time to fall asleep, number of awakenings during sleep, and EEG-derived sleep intensity. The multi-level statistical analyses consistently showed that sleep quality was virtually unaffected when >3 caffeine-containing beverages/day were compared to 0-3 beverages/day. This conclusion was further corroborated by quantifying the sleep EEG in the laboratory in habitual caffeine consumers. Compared to placebo, daily intake of 3 x 150 mg caffeine over 10 days did not strongly impair nocturnal sleep nor subjective sleep quality in good sleepers. Finally, we tested whether an engineered delayed, pulsatile-release caffeine formula can improve the quality of morning awakening in sleep-restricted volunteers. We found that 160 mg caffeine taken at bedtime ameliorated the quality of awakening, increased positive and reduced negative affect scores, and promoted sustained attention immediately upon scheduled wake-up. Such an approach could prevent over-night caffeine withdrawal and provide a proactive strategy to attenuate disabling sleep inertia. Taken together, the studies suggest that common coffee/caffeine intake habits can transiently attenuate detrimental consequences of reduced sleep virtually without disturbing subjective and objective markers of sleep quality. Nevertheless, coffee/caffeine consumption cannot compensate for chronic sleep restriction.

Sleep is generally associated with the brain but poor sleep impacts the entire body - many diseases are caused or exacerbated by sleep loss. Our work is uncovering ways in which sleep and the body interact. We found a special, two-way relationship between sleep and the gut: the gut is uniquely impacted by sleep loss, and it actively controls sleep quality. These findings could help us understand the origins of sleep as well as develop strategies to offset the negative consequences of inadequate sleep.