Luis de Lecea

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

© 2021 The Author(s)
Published by S. Karger AG, Basel

• Chapter 1 graphical abstract

The discovery of the hypocretins/orexins (HCRTs) has revolutionized sleep science in the last two decades. A combination of anatomical tracing methods, optogenetics, and pharmacology is delineating a blueprint of functional inputs and outputs of the HCRT system. Here, we discuss several models of HCRT action that involve the integration between physiological variables, circadian output, and sleep homeostasis. Generation of activity maps during the sleep-wake cycle at the cellular level will allow investigators to decipher computational frameworks modeling operations of HCRT networks.

• Ample evidence supports the notion that release of HCRT peptides stabilizes arousal.
• Integration of multiple variables at multiple timescales in HCRT neurons appears essential for HCRT function.
• Computational models of neuronal inputs to HCRT neurons based on hierarchy, redundancy, and feedback control may predict sleep-wake transitions with high accuracy.

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