Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, CA, USA.
Atlantia Clinical Trials, Cork, Ireland.
Commun Biol. 2023 Jan 19;6(1):74. doi: 10.1038/s42003-023-04409-w.
Neurons in the lateral hypothalamus expressing the neuropeptide Hypocretin, also known as orexin, are known critical modulators of arousal stability. However, their role in the different components of the arousal construct such as attention and decision making is poorly understood. Here we study Hypocretin neuronal circuit dynamics during stop action impulsivity in a Go/NoGo task in mice. We show that Hypocretin neuronal activity correlates with anticipation of reward. We then assessed the causal role of Hypocretin neuronal activity using optogenetics in a Go/NoGo task. We show that stimulation of Hypocretin neurons during the cue period dramatically increases the number of premature responses. These effects are mimicked by amphetamine, reduced by atomoxetine, a norepinephrine uptake inhibitor, and blocked by a Hypocretin receptor 1 selective antagonist. We conclude that Hypocretin neurons have a key role in the integration of salient stimuli during wakefulness to produce appropriate and timely responses to rewarding and aversive cues.
外侧下丘脑表达神经肽 Hypocretin（也称为食欲素）的神经元是已知的觉醒稳定性的关键调节剂。然而，它们在觉醒结构的不同成分（如注意力和决策制定）中的作用知之甚少。在这里，我们研究了在小鼠 Go/NoGo 任务中停止动作冲动时 Hypocretin 神经元回路的动态。我们发现 Hypocretin 神经元活动与奖励的预期相关。然后，我们使用光遗传学在 Go/NoGo 任务中评估 Hypocretin 神经元活动的因果作用。我们发现，在提示期刺激 Hypocretin 神经元会极大地增加过早反应的数量。这些作用类似于安非他命，被去甲肾上腺素摄取抑制剂托莫西汀减弱，并被 Hypocretin 受体 1 选择性拮抗剂阻断。我们得出结论，Hypocretin 神经元在整合觉醒期间的显著刺激方面起着关键作用，以对奖励和厌恶线索产生适当和及时的反应。
