PDF(Pubmed)
Abstract：
Dopamine and orexins (hypocretins) play important roles in regulating reward-seeking behaviors. It is known that hypothalamic orexinergic neurons project to dopamine neurons in the ventral tegmental area (VTA), where they can stimulate dopaminergic neuronal activity. Although there are reciprocal connections between dopaminergic and orexinergic systems, whether and how dopamine regulates the activity of orexin neurons is currently not known. Here we implemented an opto-Pavlovian task in which mice learn to associate a sensory cue with optogenetic dopamine neuron stimulation to investigate the relationship between dopamine release and orexin neuron activity in the lateral hypothalamus (LH). We found that dopamine release can be evoked in LH upon optogenetic stimulation of VTA dopamine neurons and is also naturally evoked by cue presentation after opto-Pavlovian learning. Furthermore, orexin neuron activity could also be upregulated by local stimulation of dopaminergic terminals in the LH in a way that is partially dependent on dopamine D2 receptors (DRD2). Our results reveal previously unknown orexinergic coding of reward expectation and unveil an orexin-regulatory axis mediated by local dopamine inputs in the LH.
摘要：
多巴胺和食欲素（hyprocretins）在调节奖励寻求行为中起重要作用。已知下丘脑氧化神经元投射到腹侧被盖区（VTA）的多巴胺神经元，它们可以刺激多巴胺能神经元活动。尽管多巴胺能系统和奥利克能系统之间存在相互联系，目前尚不清楚多巴胺是否以及如何调节食欲素神经元的活性。在这里，我们实施了一项opto-Pavlovian任务，其中小鼠学习将感觉提示与光遗传学多巴胺神经元刺激相关联，以研究多巴胺释放与下丘脑外侧（LH）中食欲素神经元活性之间的关系。我们发现，在光遗传学刺激VTA多巴胺神经元后，LH中的多巴胺释放可以被诱发，并且在opto-Pavlovian学习后通过提示呈现自然诱发。此外，通过局部刺激LH中的多巴胺能终末，食欲素神经元的活性也可能被上调，其方式部分依赖于多巴胺D2受体（DRD2）。我们的结果揭示了以前未知的奖赏期望的食欲素编码，并揭示了LH中局部多巴胺输入介导的食欲素调节轴。
