Abstract
The hypocretin (Hcrt) system has been implicated in a wide range of physiological functions from sleep-wake regulation to cardiovascular, behavioral, metabolic, and thermoregulagtory control. These wide-ranging physiological effects have challenged the identification of a parsimonious function for Hcrt. A compelling hypothesis suggests that Hcrt plays a role in the integration of sleep-wake neurophysiology with energy metabolism. For example, Hcrt neurons promote waking and feeding, but are also sensors of energy balance. Loss of Hcrt function leads to an increase in REM sleep propensity, but a potential role for Hcrt linking energy balance with REM sleep expression has not been addressed. Here we examine a potential role for Hcrt and the lateral hypothalamus (LH) in state-dependent resource allocation as a means of optimizing resource utilization and, as a result, energy conservation. We review the energy allocation hypothesis of sleep and how state-dependent metabolic partitioning may contribute toward energy conservation, but with additional examination of how the loss of thermoregulatory function during REM sleep may impact resource optimization. Optimization of energy expenditures at the whole organism level necessitates a top-down network responsible for coordinating metabolic operations in a state-dependent manner across organ systems. In this context, we then specifically examine the potential role of the LH in regulating this output control, including the contribution from both Hcrt and melanin concentrating hormone (MCH) neurons among a diverse LH cell population. We propose that this hypothalamic integration system is responsible for global shifts in state-dependent resource allocations, ultimately promoting resource optimization and an energy conservation function of sleep-wake cycling.
Highlights
In the 20 years since the discovery of the hypocretin/orexin (Hcrt) system, a growing diversity of physiological and neurobehavioral responses under Hcrt control has challenged identification of a unifying function
We examine the potential role of the lateral hypothalamus (LH) in regulating this output control, including the contribution from both Hcrt and melanin concentrating hormone (MCH) neurons among a diverse LH cell population. We propose that this hypothalamic integration system is responsible for global shifts in state-dependent resource allocations, promoting resource optimization and an energy conservation function of sleep-wake cycling
We recently proposed that rapid eye movement (REM) sleep cycles with NREM sleep based on thermoregulatory constraints as a means of optimizing REM sleep expression and resource allocations [37]
Summary
In the 20 years since the discovery of the hypocretin/orexin (Hcrt) system, a growing diversity of physiological and neurobehavioral responses under Hcrt control has challenged identification of a unifying function. Several important principles emerge from this mathematical modeling, including why sleep may be a better behavioral strategy than quiet wakefulness with respect to resource optimization and energy savings This modeling suggests that metabolic partitioning by state is constrained if energy deployment toward waking-related processes is maintained during the rest phase, whereas energy savings are amplified if waking-related allocations during the rest phase are eliminated [38]. This mechanism of energy conservation requires a system capable of monitoring the energy status of the organism, and integrating many key physiological variables including core and ambient temperature to provide a coordinated output to a wide range of central and peripheral tissues
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