Cited by 83Sleep and Wakefulness ResearchNeuroscience of respiration and sleepRegulation of Appetite and Obesity

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Hypocretin as a Hub for Arousal and Motivation

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Tyree, Susan M., Borniger, Jeremy C., de Lecea, Luis·2018·Frontiers in Neurology

DOI 10.3389/fneur.2018.00413PMC PMC5997825

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Abstract

The lateral hypothalamus is comprised of a heterogeneous mix of neurons that serve to integrate and regulate sleep, feeding, stress, energy balance, reward, and motivated behavior. Within these populations, the hypocretin/orexin neurons are among the most well studied. Here, we provide an overview on how these neurons act as a central hub integrating sensory and physiological information to tune arousal and motivated behavior accordingly. We give special attention to their role in sleep-wake states and conditions of hyper-arousal, as is the case with stress-induced anxiety. We further discuss their roles in feeding, drug-seeking, and sexual behavior, which are all dependent on the motivational state of the animal. We further emphasize the application of powerful techniques, such as optogenetics, chemogenetics, and fiber photometry, to delineate the role these neurons play in lateral hypothalamic functions.

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Figure 1 The hypocretin system: inputs and outputs. Hypocretin neurons receive information regarding nutritional state, emotional state, and environmental cues regarding temperature, time of day, and recent sleep history, the weight that these inputs have is very likely variable and interrelated. Hypocretin-expressing neurons are very heterogeneous, they are known to co-express numerous other genes. Additionally, hypocretin-expressing neurons are modulated by the activity of surrounding neuron populations present in the lateral hypothalamus, including melanin-concentrating hormone, leptin receptor-expressing neurons, and corticotropin releasing factor neurons. Hypocretin neurons project to many neuron populations throughout the brain, including norepinephrine, dopaminergic, and cholinergic neurons. It is via these pathways that the hypocretin system modulates the wide range of outputs related to arousal and motivated behavior. In turn, the consequences of these behaviors go on to inform the hypocretin system as to the newly updated status of the animal, and thus determine the next hypocretin-driven behavioral output.CC BY · PubMed Central

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Authors: Tyree, S. M., Borniger, J. C., & de Lecea, L.
Affiliations: Stanford University (US)
ORCID: Tyree, Susan M.
Borniger, Jeremy C.
Venue: Frontiers in Neurology
Publisher: Frontiers Media SA
Published: 2018-06-06
Volume: 9
Pages: 413-413
ISSN: 1664-2295 (ISSN-L)
DOI: 10.3389/fneur.2018.00413
PMC: PMC5997825
OpenAlex: W2806993167
Cited by: 83
References: 236
Citations by year: 2026: 5 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 15 · 2021: 12 · 2020: 19 · 2019: 10 · 2018: 3
FWCI: 1.47
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Frontiers in Neurology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Neurological Foundation of New Zealand
Foundation for the National Institutes of Health (F32MH11543, 5R01MH087592, R01MH1026380, 1R01AG047671)
Boehringer Ingelheim
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: hypocretin/orexin neurons, lateral hypothalamus, arousal, motivation, sleep-wake regulation, hyperarousal, stress-induced anxiety, feeding behavior, drug-seeking behavior, sexual behavior, optogenetics, chemogenetics, fiber photometry

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Hypocretin as a Hub for Arousal and Motivation

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