Abstract
The role of the hypothalamic preoptic area (POA) in arousal state regulation has been studied since Constantin von Economo first recognized its importance in the early twentieth century. Over the intervening decades, the POA has been shown to modulate arousal in both natural (sleep and wake) as well as drug-induced (anesthetic-induced unconsciousness) states. While the POA is well known for its role in sleep promotion, populations of wake-promoting neurons within the region have also been identified. However, the complexity and molecular heterogeneity of the POA has made distinguishing these two populations difficult. Though multiple lines of evidence demonstrate that general anesthetics modulate the activity of the POA, the region’s heterogeneity has also made it challenging to determine whether the same neurons involved in sleep/wake regulation also modulate arousal in response to general anesthetics. While a number of studies show that sleep-promoting POA neurons are activated by various anesthetics, recent work suggests this is not universal to all arousal-regulating POA neurons. Technical innovations are making it increasingly possible to classify and distinguish the molecular identities of neurons involved in sleep/wake regulation as well as anesthetic-induced unconsciousness. Here, we review the current understanding of the POA’s role in arousal state regulation of both natural and drug-induced forms of unconsciousness, including its molecular organization and connectivity to other known sleep and wake promoting regions. Further insights into the molecular identities and connectivity of arousal-regulating POA neurons will be critical in fully understanding how this complex region regulates arousal states.
Highlights
Prior to the twentieth century, sleep was considered to be a passive process, caused not by specific neural circuits but rather by reduced sensory input that led to low levels of brain activity
This study found that sleep-active median preoptic area (MnPO) neurons are more responsive to sleep deprivation at post-natal day 30 (P30) compared to P22 (Gvilia et al, 2017)
Because the ventrolateral preoptic area (VLPO) and MnPO contain the highest densities of sleep-active neurons, the majority of work investigating the role of the preoptic area (POA) in anesthetic hypnosis has focused on these two regions, the VLPO
Summary
Prior to the twentieth century, sleep was considered to be a passive process, caused not by specific neural circuits but rather by reduced sensory input that led to low levels of brain activity. This led him to propose the existence of a “sleep center” in the anterior hypothalamus and a corresponding “wake center” in the posterior hypothalamus that act in opposition to actively regulate arousal state (von Economo, 1930) Since these original findings, the existence of hypothalamic circuits involved in regulating arousal state has been repeatedly confirmed across a variety of mammalian species. Failure to properly regulate arousal state can have serious costs, including increased risk of obesity, cardiovascular disease, and impaired cognition from improper sleep/wake regulation (Everson, 1993; Taheri, 2006; Gallicchio and Kalesan, 2009; Vgontzas et al, 2009; Buxton and Marcelli, 2010; Cappuccio et al, 2010; Besedovsky et al, 2012)., as well as intraoperative awareness and delayed emergence from anesthesia (Mesa et al, 2000; Sebel et al, 2004; Mashour and Avidan, 2015; Sanders et al, 2017). New technical innovations are highlighted that should enable more refined targeting of POA neuronal subtypes and greatly enhance our understanding of how this complex region regulates arousal states
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