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.

瘙痒是一种令人不愉快的感觉，会触发抓挠行为。在确定周围和脊髓水平的瘙痒机制方面已经取得了很大进展，但是，大脑中的瘙痒回路仍未开发。我们先前发现前扣带回皮质（ACC）到背侧纹状体（DMS）输入调节了组胺引起的瘙痒感觉，但是如何将瘙痒信息传递到ACC尚不清楚。在这里，我们证明了在组织胺能性瘙痒过程中丘脑前丘脑核（AM）被激活，并且在AM和ACC之间存在相互的神经元投射。AM和ACC之间的断开导致与组织胺有关的瘙痒行为明显减少，但与非组织胺有关的瘙痒行为却没有明显减少。AM-ACC的光遗传激活，而不是ACC-AM的预测引起组胺能痒感。