Local network regulation of orexin neurons in the lateral hypothalamus

Abstract

Obesity and inadequate sleep are among the most common causes of health problems in modern society. Thus, the discovery that orexin (hypocretin) neurons play a pivotal role in sleep/wake regulation, energy balance, and consummatory behaviors has sparked immense interest in understanding the regulatory mechanisms of these neurons. The local network consisting of neurons and astrocytes within the lateral hypothalamus and perifornical area (LH/PFA), where orexin neurons reside, shapes the output of orexin neurons and the LH/PFA. Orexin neurons not only send projections to remote brain areas but also contribute to the local network where they release multiple neurotransmitters to modulate its activity. These neurotransmitters have opposing actions, whose balance is determined by the amount released and postsynaptic receptor desensitization. Modulation and negative feedback regulation of excitatory glutamatergic inputs as well as release of astrocyte-derived factors, such as lactate and ATP, can also affect the excitability of orexin neurons. Furthermore, distinct populations of LH/PFA neurons express neurotransmitters with known electrophysiological actions on orexin neurons, such as melanin-concentrating hormone, corticotropin-releasing factor, thyrotropin-releasing hormone, neurotensin, and GABA. These LH/PFA-specific mechanisms may be important for fine tuning the firing activity of orexin neurons to maintain optimal levels of prolonged output to sustain wakefulness and stimulate consummatory behaviors. Building on these exciting findings should shed further light onto the cellular mechanisms of energy balance and sleep-wake regulation.

The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

“…The ARC and VMN are well known for the regulation of satiety, metabolic homeostasis, and hypoglycemic counter-regulation responses, especially the control of glucose release, among other functions (43–46). The LHA is an orexigenic center involved in appetite, wakefulness, and energy expenditure (47). As such, it is intuitive that specific neuronal circuitry within these regions may also have a direct influence on pancreatic islet physiology, especially the secretion of insulin and glucagon.…”

The orexin neuropeptide system: physical activity and hypothalamic function throughout the aging process

“…It must be emphasized that orexin neurons are part of a local (intra-hypothalamic) and global (across the brain) network involved in the control of behavior and energy balance (Peyron et al, 1998; Burt et al, 2011; Kotz et al, 2012). Thus, when considering specific mechanisms that contribute to obesity, orexin signaling is but one part of an interconnected system influenced by multiple genetic and environmental factors.…”

Alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness

“…The MCH neuron population has been implicated in feeding behavior, locomotor activity, autonomic nervous functions, and sleep regulation (Guyon et al, 2009;Peyron et al, 2009;Tsunematsu et al, 2014). In particular, MCH neurons exert an inhibitory influence on OX-A neurons, fine-tuning their final output (Adamantidis et al, 2008;Rao et al, 2008;Burt et al, 2011), and can counteract the wake-promoting activity of arousal neurons (Konadhode et al, 2013), promoting sleep (Jones and Hassani, 2013).…”