Genetic sleep deprivation: using sleep mutants to study sleep functions

Abstract

Sleep is a fundamental conserved physiological state in animals and humans. It may serve multiple functions, ranging from energy conservation to higher brain operation. Understanding sleep functions and the underlying mechanisms requires the study of sleeplessness and its consequences. The traditional approach to remove sleep is sleep deprivation ( SD ) by sensory stimulation. However, stimulation‐induced SD can be stressful and can cause non‐specific side effects. An emerging alternative method is “genetic SD ”, which removes sleep using genetics or optogenetics. Sleep requires sleep‐active neurons and their regulators. Thus, genetic impairment of sleep circuits might lead to more specific and comprehensive sleep loss. Here, I discuss the advantages and limits of genetic SD in key genetic sleep model animals: rodents, zebrafish, fruit flies and roundworms, and how the study of genetic SD alters our view of sleep functions. Genetic SD typically causes less severe phenotypes compared with stimulation‐induced SD , suggesting that sensory stimulation‐induced SD may have overestimated the role of sleep, calling for a re‐investigation of sleep functions.

Sleep deprivation and stress: a reciprocal relationship

“…This re-normalization of synaptic strength could favour memory acquisition, consolidation and integration during sleep [6]. These interrelated phenomena have been described as vital for the organism, both ontogenetically and phylogenetically [7].…”

“…After light-sensitive ion channels, or designer receptors exclusively activated by designer drugs, are expressed in targeted cells, optogenetics allows neuronal depolarization or hyperpolarization with pulses of light while chemogenetics provides the royalsocietypublishing.org/journal/rsfs Interface Focus 10: 20190092 ability to modulate neuronal firing for several hours with the single administration of a designer drug. With the advancements in mapping brain sleep circuitry [1], 'genetic sleep deprivation' can now be accomplished without stress-associated sensory stimulation via the inhibition of sleep-promoting neurons or the activation of wake-promoting neurons [7]. This could be done by directly targeting sleep-or wake-active neurons, or through the manipulation of neuronal populations that stimulate wake-promoting, or inhibit sleepinducing, neurons.…”

Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

“…It is difficult to keep animals awake for a long time because a powerful homeostatic mechanism drives recovery of lost sleep; this compensatory mechanism is not well understood but is evident in rebound sleep seen after a night of sleep deprivation (i.e., animals sleep instead of being active) (Allada et al, 2017;Hendricks et al, 2000;Huber et al, 2004;Shaw et al, 2000). As can be intuited (Bringmann, 2019), to reveal the full consequence of sleep loss, it is likely necessary to bypass the mechanisms that drive rebound sleep. Crucially, lack of such drive should not eliminate the physiological need for sleep, the same way that a lack of appetite would not eliminate the need for nutrients.…”

Salvianolic Acid B improves cognitive impairment by inhibiting neuroinflammation and decreasing Aβ level in Porphyromonas gingivalis-infected mice

“…It has been well documented that inadequate sleep is detrimental to human health [4,5]. The traditional way to study sleeplessness and its consequences is sleep deprivation through sensory stimulation [6]. Sleep deprivation has long been known to impair neurobehavior.…”