Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Neuropharmacology. 2020 May 15;168:108028. doi: 10.1016/j.neuropharm.2020.108028. Epub 2020 Mar 6.
Itch is an unpleasant feeling that triggers scratching behavior. Much progress has been made in identifying the mechanism of itch at the peripheral and spinal levels, however, itch circuits in the brain remain largely unexplored. We previously found that anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) inputs modulated histamine-induced itch sensation, but how itch information was transmitted to ACC remained unclear. Here, we demonstrated that the anteromedial thalamic nucleus (AM) was activated during histaminergic itch, and there existed reciprocal neuronal projections between AM and ACC. Disconnection between AM and ACC resulted in a significant reduction of histaminergic, but not nonhistaminergic, itch-related scratching behavior. Optogenetic activation of AM-ACC, but not ACC-AM, projections evoked histaminergic itch sensation. Thus, our studies firstly reveal that AM is critical for histaminergic itch sensation and AM-ACC projections modulate histaminergic itch-induced scratching behavior.
痒是一种不愉快的感觉，会引发搔抓行为。在外周和脊髓水平上，人们在识别痒的机制方面已经取得了很大的进展，然而，大脑中的痒回路在很大程度上仍未被探索。我们之前发现，扣带前皮质（ACC）到背内侧纹状体（DMS）的输入调节组胺诱导的痒感，但痒信息如何传递到 ACC 仍不清楚。在这里，我们证明了在前丘脑核（AM）在组胺能性痒时被激活，并且 AM 和 ACC 之间存在相互的神经元投射。AM 和 ACC 之间的断开导致组胺能性，但不是非组胺能性，与痒相关的搔抓行为显著减少。光遗传学激活 AM-ACC，但不是 ACC-AM，投射引发组胺能性痒感。因此，我们的研究首次表明，AM 对组胺能性痒感至关重要，并且 AM-ACC 投射调节组胺能性痒诱导的搔抓行为。
