The projection from the prelimbic cortex to the ventral tegmental area negatively regulates 5-HT-induced itch-scratching and positively regulates itch-related aversion in rats

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-02-28 DOI:10.1016/j.brainresbull.2025.111283

Xing-Yu Lu , Jun-Fei Teng , Juan Yao , Xuan Li , Bing Wu , Xue-Qiang Hu , Ping Wang , Xiao-Qian Jiang , Jian-Feng Sui , Ke-Hui Hu , Yue-Ming Xu , Shu-Lei Liu

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引用次数: 0

Abstract

Direct and indirect evidence suggests that the prelimbic cortex (PrL) and the ventral tegmental area (VTA) are the key brain regions involved in the regulation of itch sensation and itch-related emotions. The PrL projects widely to various cortical and subcortical brain regions, with the VTA being one of the main targets of PrL descending projections. However, the differential roles of the PrL-VTA pathway in the regulation of itch sensation and itch-related emotion remain unclear. In this study, we investigated 5-HT-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of PrL-VTA projection activity. Pharmacogenetic inhibition of a subpopulation of PrL glutamatergic neurons projecting to the VTA increased 5-HT-induced itch-scratching behavior but alleviated the conditioned place aversion behavior accompanying acute itch, indicating that the descending pathway from the PrL to the VTA negatively controls itch sensation but positively regulates itch-related negative emotion. GABAergic and DAergic neurons in the VTA are potentially responsible for mediating the opposite regulatory effects of PrL-VTA projections on itch sensation and emotion, respectively. These results are helpful for further understanding the neuroregulatory mechanisms of different components of itch.

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直接和间接证据表明，前边缘皮层（PrL）和腹侧被盖区（VTA）是参与调节痒觉和痒相关情绪的关键脑区。PrL广泛投射到大脑皮层和皮层下的各个脑区，其中VTA是PrL下降投射的主要目标之一。然而，PrL-VTA通路在调控痒觉和痒相关情绪中的不同作用仍不清楚。在这项研究中，我们研究了药物基因抑制 PrL-VTA 投射活动后 5-HT 诱导的大鼠条件性场所厌恶（CPA）和抓痒痒行为。药物抑制投射到VTA的PrL谷氨酸能神经元亚群会增加5-HT诱导的抓痒行为，但会减轻伴随急性痒的条件性场所厌恶行为，这表明从PrL到VTA的下行通路对痒感有负面控制，但对痒相关的负面情绪有正面调节。VTA中的GABA能神经元和DA能神经元可能分别负责介导PrL-VTA投射对痒感和情绪的相反调节作用。这些结果有助于进一步了解痒的不同成分的神经调节机制。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.