Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons
Natalie J. Michael, Joel K. Elmquist
Natalie J. Michael, Joel K. Elmquist
Published August 17, 2020
Citation Information: J Clin Invest. 2020;130(9):4540-4542. https://doi.org/10.1172/JCI140585.
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Commentary

Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons

Abstract

Orexin/hypocretin neurons located in the lateral hypothalamus play a critical role in the maintenance of arousal and contribute to the regulation of multiple homeostatic and behavioral processes. In this issue of the JCI, Tan and Hang et al. report that feeding a high-fat diet to mice compromised the function of the orexin system, leading to impairments in reward-seeking and active coping mechanisms. The researchers observed changes at the cellular and circuit levels suggesting that reduced excitability of orexin neurons affects behavior through induction of a hypoarousal state.

Authors

Natalie J. Michael, Joel K. Elmquist

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Figure 1

Obesity-induced cellular and circuit level changes in the orexin system are associated with maladaptive behavioral responses.

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Obesity-induced cellular and circuit level changes in the orexin system ...
Chronic HFF alters glutamatergic inputs to orexin/hypocretin neurons (Ox/Hcrt), thereby increasing overall inhibitory tone and inducing a state of hypoarousal. Altered cellular activity of orexin neurons influences the activity of downstream neural networks in the lateral hypothalamus and hippocampus and decreases reward-seeking and coping behaviors. Chemogenetic activation of orexin neurons reverses changes in network activity and corrects the behavioral consequences of HFF (14). GluR, glutamate receptor; D1R, dopamine 1 receptor; hM3Dq, chemogenic receptor.