Sleep and Restorative Processes
May 4-11, 2024
Director: Chiara Cirelli
University of Madison-Wisconsin, Madison, USA
Faculty:
Luis de Lecea, Stanford University, USA
Stephan Sigrist, Freie Universität Berlin, Germany
Giulio Tononi, University of Madison-Wisconsin, Madison, USA
Jason Rihel, University College, London, UK
Janet Mullington, Harvard Medical School, Cambridge, USA
Kenneth Wright, University of Colorado, Boulder, USA
Chiara Cirelli, University of Madison-Wisconsin, Madison, USA
Every time we fall asleep, we lose the ability to monitor what is happening around us and respond promptly to a potential threat. The mere fact that we still sleep every day, and likewise all animal species that have been carefully studied so far, suggests that sleep serves essential functions. During the Advanced Course, we will discuss many of the benefits that sleep provides for the brain and the body. Cirelli, Rihel and Sigrist will discuss new evidence in mice, zebrafish and flies, linking the need to sleep to neuronal activity and plasticity during waking and the role of sleep in promoting synaptic homeostasis. De Lecea will examine how ageing affects sleep, its restorative effects, and the use of noninvasive ultrasound methods for sleep interventions. Tononi will review the role of specific sleep waves in restorative processes and non-pharmacological methods to enhance them. Mullington will discuss how sleep lowers the risk of infections and the mechanisms by which sleep loss affects the innate and adaptive immune system. Wright will analyze how circadian misalignment and insufficient sleep may contribute to dysregulated metabolic physiology and metabolic diseases.
Kenneth Wright
The Role of Sleep and Circadian Rhythms in Metabolic Physiology and Health
Sleep and circadian rhythms are fundamentally involved in metabolic physiology and health. Disruptions to sleep and circadian rhythms result in dysregulated physiology that can contribute to metabolic diseases (e.g., Obesity, Type-2 Diabetes). Talks will 1) discuss integrative aspects of sleep, circadian rhythms and metabolic physiology; 2) highlight how circadian misalignment and insufficient sleep may contribute to dysregulated metabolic physiology and metabolic diseases and discuss contributing mechanisms, including changes in the transcriptome, proteome, metabolome, microbiome and endocrine physiology; 3) describe the potential for countermeasures to improve metabolic health outcomes under conditions were sleep and circadian disturbance cannot be avoided.
Jason Rihel
The Pressure to Sleep: Physiological Drivers, Encoders, and Executing Circuits
Sleep need is a function of prior wakefulness, but the molecular and circuit mechanisms involved in regulating sleep pressure mostly remain a mystery. I will discuss recent genetic and imaging evidence from animal models such as zebrafish that 1) implicate brain-wide neuronal and glial activity in the modulation of sleep pressure; 2) identify molecular signaling components involved in conveying sleep need; and 3) localize the output of sleep homeostasis to specific neuronal circuits. I will also discuss recent evidence that suggests that sleep pressure serves as a regulatory gate for synaptic renormalization during sleep. Finally, I will examine how molecules associated with neurodegenerative disease may interact with these sleep-regulatory systems in both normal and disease states to perturb sleep behavior.
Luis de Lecea
Sleep Fragmentation and Neuromodulation
The sequence of vigilance states is tightly regulated, and sleep continuity is likely an essential feature of its function. Work over the past two decades has demonstrated that the neuropeptide Hypocretin (also known as Orexin) has a critical role in controlling the boundaries between arousal states and sleep architecture. I will discuss how sleep continuity affects learning and social memory in mammals and will describe a new mechanism underlying sleep fragmentation associated with aging. I will also present data from multiple laboratories suggesting that DNA repair is an important cellular function for sleep and a likely link to neurodegeneration. Finally, I will describe attempts to non-invasively modulate arousal circuits and optimize sleep quality.
Chiara Cirelli
Sleep and Synpatic Plasticity
Partial sensorimotor disconnection is a defining feature of sleep and one of the strongest indicators that sleep fulfils some essential restorative functions that require the brain to be offline. If these functions were independent of sensory disconnection, evolution would have found a way to carry them out more safely during waking, when we can promptly react to the environment. Thus, sensory disconnection puts specific constraints on any idea about its restorative functions. Topics of discussion will include 1) the many open questions regarding the mechanisms underlying sensorimotor disconnection during sleep; 2) the evidence that a key function of sleep is to maintain synaptic homeostasis; 3) the relative roles of neuronal activity and plasticity in determining sleep need; 4) the specific roles of NREM sleep and REM sleep in sleep-dependent synaptic homeostasis; 5) the homeostatic regulation of sharp waves in the hippocampus.
Janet Mullington
Sleep and the Immune System
Sleep supports immune regulation. If people don’t get adequate sleep, they are at increased risk of developing respiratory infections. If adequate sleep is not obtained following vaccination, antibody titers do not develop as well as when sleep is permitted. Sleep partially supports host defenses through regulation of the endocrine and metabolic pathways, particularly the hypothalamic-pituitary-adrenal axis, as well as through physiological and psychological stress reduction mechanisms. We will discuss what is known about the role of sleep in host defense mechanisms from an integrative physiology perspective and then discuss key gaps in knowledge.
SARS-CoV-2 has presented the world with a tragic challenge to health. Long COVID is a term used to describe the continuation or resurgence of symptoms after more than three months. This presentation of post-viral sequelae brought with it an opportunity to study the risks associated with the lack of resolution of symptomatic illness, as seen in Long COVID. We will examine lessons learned through the pandemic about the role of sleep in recovery from COVID. Sleep as a window into the brain in post-viral disease and what it can reveal about the integrity of the defense against neurodegenerative disease will also be discussed.
Stephan Sigrist
Widespread and diverse phenomenon of sleep: local and brain-wide plasticity and activity integrate into the coding of sleep need and cognitive function
Sleep, as a highly conserved animal and human behaviour, 1) is likely an integrated behavioural output of a global and widespread origin, and 2) has broader and diverse effects on synaptic plasticity and function. How global and brain-wide synaptic plasticity and activity couple to integrate into specific circuits for the execution of sleep remains largely unknown. I will discuss 1) recent progress in brain molecular signatures monitoring sleep needs, 2) new genetic evidence in the regulation of sleep homeostasis, and 3) recent convergent mechanisms of the execution of sleep and sleep homeostasis by circuit-specific and brain-wide plasticity. I will also talk about the role of presynaptic vesicle release properties in sleep regulation. Finally, I will discuss the new evidence for understanding the molecular mechanisms of the interaction between sleep regulation and memory formation, especially in the context of healthy brain ageing.
Giulio Tononi
Sleep Waves and Their Restorative Role in Cognition
To be published shortly