Sci Adv:陆军军医大学吴广延团队发现皮层编码痒觉的神经元群

2022-08-03 周科 “神经周K”公众号

腹外侧眶皮层(VLO)是调控痛觉的关键脑区。2022年7月29日陆军军医大学基础医学院吴广延研究团队发现了VLO存在一类编码痒觉的神经元群。

胃泌素释放肽 (GRP) 作为一种重要的神经递质,可将非组胺能瘙痒从背根神经节(DRG)的初级感觉神经元传递到脊髓中表达 GRP 受体 (GRPR) 的神经元。在脊髓水平,表达 GRPR 的神经元是被认为选择性参与处理瘙痒信息而不是疼痛。

但是,脊髓 GRP 中间神经元接受来自疼痛和瘙痒初级感觉神经元的单突触输入,清除这些 GRP 神经元后减弱痒觉,但增加了疼痛反应,这与上文存在矛盾之处。多个假说能够解释这个矛盾:区分痒觉-痛觉强度理论认为同一群神经元在受到刺激后在脊髓和DRG分别产生痒觉和痛觉。详细:Nature:诺奖得主揭示离子通道分子Piezo 1转导机械性痒觉信息Neuron:研究发现脑内痒觉调控神经元

腹外侧眶皮层(VLO)是调控痛觉的关键脑区。2022年7月29日陆军军医大学基础医学院吴广延研究团队发现了VLO存在一类编码痒觉的神经元群。

1

VLO可同时编码痒觉和痛觉信息

研究人员发现化学遗传学慢性抑制或光遗传学抑制VLO区域神经元后能够抑制氯喹或内皮素-1引起的瘙痒行为,也能减弱暴露在化合物异硫氰酸烯丙酯(AITC)诱发痛觉反应。这就表明VLO脑区可同时编码痒觉和痛觉信息。

光纤钙成像技术记录到在痒觉诱发的瘙痒和痛觉诱发的舔舐行为中,VLO区域兴奋性神经元活性增强,抑制性神经元活性降低。慢性抑制VLO区域兴奋性神经元后可减弱痒觉和痛觉,而在抑制该区域抑制性神经元后增强痒觉和痛觉。

图1:抑制VLO区域神经元后能够同时减弱痒觉和痛觉

2

痒觉特异性和痛觉抑制性神经元

功能和结构的差异性

5-羟色胺(5-HT)注射到大鼠颈部可诱发痒觉,并激活VLO脑区神经元。他们进一步通过四环素关闭系统结合病毒载体工具实现对5-HT 激活的VLO脑区神经元进行标记,这类神经元被称为痒觉特异性神经元。

化学遗传学特异性抑制上述痒觉特异性神经元后可明显降低5-HT诱发的痒觉,但不影响AITC或福尔马林等化合物诱发痛觉反应。在没有瘙痒原和过敏原情况下,光激活这类痒觉神经元并不会引起瘙痒行为,但存在瘙痒原和过敏原下,激活这类神经元能够进一步增强痒觉。

通过上述类似的方法对AITC诱发痛觉响应的神经元进行标记,称为痛觉特异性神经元,化学抑制或光抑制能够这类痛觉神经元可明显减弱痛觉相关行为,但不影响痒觉。光激活这类痛觉神经元后可增强AITC或辣椒素诱发的痛觉。

光纤钙成像技术记录到在5HT诱发痒觉过程中,仅VLO脑区痒觉神经元活性增加,痛觉神经元活性几乎无变化。在AITC诱发痛觉反应中仅痛觉神经元活性增加,痒觉神经元几乎无变化,这表明这两类神经元功能差异性。

进一步通过Tet-Off/On系统对痒觉特定神经元和痛觉特定神经元进行同时标记,结果发现这两类神经元重叠的比例仅为2.86%。此外,病毒示踪实验揭示痒觉特定神经元主要投射到梨状皮层,而痛觉特异性神经元主要投射到岛叶皮层,这表明这两类神经元解剖学结构差异性。

VLO区域由抑制性神经元和兴奋性锥体神经元组成,免疫荧光实验发现上述70%痒觉特异性神经元为兴奋性神经元,9.57%为抑制性神经元,而上述78%痛觉神经元为兴奋性神经元,8%为抑制性神经元。

图2:痒觉神经元与痛觉神经元存在明显差异性

总结

本文通过病毒载体工具揭示了腹外侧眶皮层存在两类结构、功能差异的神经元群,分别编码痒觉和痛觉信息。

原始出处:

Jiang Shan, et al. Itch-specific neurons in the ventrolateral orbital cortexselectively modulate the itch processing,Jiang et al., Sci. Adv. 8, eabn4408 (2022).

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