Abstract:
C-nociceptors (C-Ncs) and non-nociceptive C-low threshold mechanoreceptors (C-LTMRs) are two subpopulations of small unmyelinated non-peptidergic C-type neurons of the dorsal root ganglia (DRGs) with central projections displaying a specific pattern of termination in the spinal cord dorsal horn. Although these two subpopulations exist in several animals, remarkable neurochemical differences occur between mammals, particularly rat/humans from one side and mouse from the other. Mouse is widely investigated by transcriptomics. Therefore, we here studied the immunocytochemistry of murine C-type DRG neurons and their central terminals in spinal lamina II at light and electron microscopic levels. We used a panel of markers for peptidergic (CGRP), non-peptidergic (IB4), nociceptive (TRPV1), non-nociceptive (VGLUT3) C-type neurons and two strains of transgenic mice: the TAFA4Venus knock-in mouse to localize the TAFA4+ C-LTMRs, and a genetically engineered ginip mouse that allows an inducible and tissue-specific ablation of the DRG neurons expressing GINIP, a key modulator of GABABR-mediated analgesia. We confirmed that IB4 and TAFA4 did not coexist in small non-peptidergic C-type DRG neurons and separately tagged the C-Ncs and the C-LTMRs. We then showed that TRPV1 was expressed in only about 7% of the IB4+ non-peptidergic C-Ncs and their type Ia glomerular terminals within lamina II. Notably, the selective ablation of GINIP did not affect these neurons, whereas it reduced IB4 labeling in the medial part of lamina II and the density of C-LTMRs glomerular terminals to about one half throughout the entire lamina. We discuss the significance of these findings for interspecies differences and functional relevance.
摘要:
C-伤害感受器(C-Ncs)和非伤害性C-低阈值机械感受器(C-LTMR)是背根神经节(DRG)的两个小的无髓鞘非肽能C型神经元亚群,其中央投影显示出特定的模式脊髓背角终止。尽管这两个亚群存在于几种动物中,哺乳动物之间存在显著的神经化学差异,特别是一侧的大鼠/人和另一侧的小鼠。通过转录组学广泛研究小鼠。因此,我们在这里研究了小鼠C型DRG神经元的免疫细胞化学及其在脊髓层II中的中央末端。我们使用了一组肽能标记物(CGRP),非肽能(IB4),伤害性(TRPV1),非伤害性(VGLUT3)C型神经元和两株转基因小鼠:TAFA4Venus敲入小鼠定位TAFA4C-LTMR,和一个基因工程的ginip小鼠,可以诱导和组织特异性消融表达GINIP的DRG神经元,GABABR介导的镇痛的关键调节剂。我们证实IB4和TAFA4在小的非肽能C型DRG神经元中不共存,并分别标记了C-Ncs和C-LTMR。然后,我们发现TRPV1仅在II层的IB4非肽能C-Ncs及其Ia型肾小球末端的约7%中表达。值得注意的是,GINIP的选择性消融不会影响这些神经元,而它将II层内侧的IB4标记和C-LTMR肾小球末端的密度降低到整个层的一半。我们讨论了这些发现对种间差异和功能相关性的意义。