Long Jun-Hui, Wang Pu-Jun, Li Zhi-Fang, Yao Juan, Li Xuan, Wu Bing, Sui Jian-Feng, Liao Jun, Wang Ping, Li Xiao-Feng, Liu Shu-Lei
Department of Dermatology, The 958th Army Hospital of the Chinese People's Liberation Army, China.
Department of Foreign Languages, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China.
Behav Brain Res. 2023 Apr 12;443:114306. doi: 10.1016/j.bbr.2023.114306. Epub 2023 Jan 20.
Itch is an unpleasant sensation followed by an intense desire to scratch. Previous researches have advanced our understanding about the role of anterior cingulate cortex and prelimbic cortex in itch modulation, whereas little is known about the effects of retrosplenial cortex (RSC) during this process. Here we firstly confirmed that the neuronal activity of dysgranular RSC (RSCd) is significantly elevated during itch-scratching processing through c-Fos immunohistochemistry and fiber photometry recording. Then with designer receptors exclusively activated by designer drugs approaches, we found that pharmacogenetic inhibition of global RSCd neurons attenuated the number of scratching bouts as well as the cumulative duration of scratching bouts elicited by both 5-HT or compound 48/80 injection into rats' nape or cheek; selective inhibition of the pyramidal neurons in RSCd, or of the excitatory projections from caudal anterior cingulate cortex (cACC) to RSCd, demonstrated the similar effects of decreasing itch-related scratching induced by both 5-HT or compound 48/80. Pharmacogenetic intervention of the neuronal or circuitry activities did not affect rats' motor ability. This study presents direct evidence that pyramidal neurons in RSCd, and the excitatory projection from cACC to RSCd are critically involved in central regulation of both histaminergic and nonhistaminergic itch.
瘙痒是一种令人不适的感觉，随后会产生强烈的搔抓欲望。先前的研究增进了我们对前扣带回皮质和前边缘皮质在瘙痒调节中作用的理解，而关于 retrosplenial 皮质（RSC）在此过程中的作用知之甚少。在这里，我们首先通过 c-Fos 免疫组化和光纤光度记录证实，在瘙痒 - 搔抓过程中，颗粒减少的 RSC（RSCd）的神经元活动显著升高。然后，通过设计药物特异性激活的设计受体方法，我们发现对整体 RSCd 神经元的药物遗传学抑制减弱了 5 - HT 或化合物 48/80 注射到大鼠颈部或脸颊所引发的搔抓发作次数以及搔抓发作的累积持续时间；对 RSCd 中的锥体神经元或从尾侧前扣带回皮质（cACC）到 RSCd 的兴奋性投射的选择性抑制，显示出对 5 - HT 或化合物 48/80 诱导的与瘙痒相关的搔抓减少的类似效果。对神经元或神经回路活动的药物遗传学干预并未影响大鼠的运动能力。这项研究提供了直接证据，表明 RSCd 中的锥体神经元以及从 cACC 到 RSCd 的兴奋性投射在组胺能和非组胺能瘙痒的中枢调节中起关键作用。
