Reward prediction is encoded by orexin neuron activity during motivated behavior
Abstract
Orexin neurons regulate physiological functions, such as energy homeostasis, wakefulness, and motivated behaviors. However, studies linking orexin neuron activity to behavior via selectively activating/inactivating these inputs in a temporally controlled manner in rats are scarce. Here, we examined the role that orexin neurons play in motivated behavior in transgenic rats using cell type–specific fiber photometry and optogenetic manipulation. Using chemogenetics, we found that motivation for a reward increased when orexin neurons were activated. Furthermore, during motivated behavior, orexin neuron activity changed dynamically: Activity increased during reward prediction and decreased after reward receipt. When an unexpected event occurred (i.e., not obtaining an expected reward), increased orexin activity was sustained. Notably, orexin activity strengthened with increasing effort. Optogenetic inhibition of orexin neuron activation during reward prediction and treatment with an orexin 1-receptor antagonist reduced reward-seeking behavior. Therefore, orexin is crucial for linking predicted expectations with motivated behavior. Moreover, optimization of orexin activity is necessary to overcome difficulties during motivated behaviors.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Yutao Dong
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Sheikh Mizanur Rahaman
Stress Recognition and Response, Research Institute of Environmental Medicine, Nagoya University
Wenjun Zhu
Ayumu Inutsuka
Department of Physiology, Aichi Medical University
Daisuke Ono
Stress Recognition and Response, Research Institute of Environmental Medicine, Nagoya University
Rinako Tanaka
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Tetsuo Matsuzaki
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Eiji Shibata
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Madoka Isobe
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Shuntaro Izawa
Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research
Akihiro Yamanaka
Chinese Institute for Brain Research
Kiyofumi Yamada
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
Hiroyuki Mizoguchi
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine