痒觉是重要的躯体感觉，但痒觉传递的中枢神经环路还很不清楚。脊髓是感觉信息初级整合中枢，痒觉信息在脊髓的传递受到来自脑干的5-HT、去甲肾上腺素等递质的下行调节。下丘脑A11区多巴胺（DA）能神经元存在向脊髓的投射，但是否参与痒觉调控还知之甚少。我们预实验结果显示鞘内注射多巴胺D1受体（D1R）拮抗剂或特异性消除D1R阳性神经元缓解了急性痒，具体的神经环路值得深入研究。为此，本项目将采用急慢性痒模型结合化学遗传、光遗传、形态学、药理学、分子生物学、电生理学、钙成像、神经示踪等方法，研究（1）脊髓中D1R和D1R阳性神经元在急慢性痒中的作用及D1R阳性神经元的分布和电生理特征；（2）脊髓D1R参与痒觉调控的局部神经环路和分子机制；（3）投射到脊髓的DA能神经元的定位及上游神经环路。本研究不但系统阐明脊髓D1R参与痒觉调控的神经环路和分子基础，也将为临床发展治疗慢性痒的新方法提供策略和理论依据。

Itch is a vital somatic sensation. However, the neurocircuits involved in itch transmission in central nervous system are far from clear. The spinal cord is the primary center for the integration of sensory information. The transmission of itch in the spinal cord is modulated by descending systems such as 5-HT and NE pathways from the brainstem. Hypothalamus A11 dopaminergic (DAergic) neurons project to the spinal cord, but it remains largely unknown whether these DAergic neurons are involved in itch modulation. Our preliminary experimental data show that intrathecal injection of D1 receptor (D1R) antagonist or ablation of D1R-positive (D1R+) neurons in the spinal cord alleviated acute itch. Therefore, it is valuable to deeply investigate the involved neurocircuits. This project will utilize the acute and chronic itch model combining with the chemogenetics, optogenetics, morphology, pharmacology, molecular biology, electrophysiology, calcium imaging, and neuronal tracing methods to investigate: (1) The role of spinal D1R and D1R+ neurons in acute and chronic itch, and the location and electrophysiological characteristics of D1R+ neurons; (2) The local neurocircuits and molecular mechanisms of spinal dorsal horn D1R in the itch regulation; (3) The location of the DAergic neurons projecting to the spinal cord, and the input regions to these DAergic neurons in the brain. This project will not only systemically demonstrate the neurocircuits and molecular basis involved in spinal D1R-modulating itch transmission, but also provide new strategies and theoretical foundations for the development of novel antipruritic therapy in clinic.