Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8577, Japan.
Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan; Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, Niigata 950-3198, Japan.
Exp Neurol. 2021 Jan;335:113493. doi: 10.1016/j.expneurol.2020.113493. Epub 2020 Oct 2.
We used the immunotoxin 192 immunoglobulin G-saporin to produce a selective cholinergic lesion in the nucleus basalis of Meynert (NBM) of rats and investigated whether the NBM lesion led to tactile hypersensitivity in the forepaw. The paw mechanical threshold test showed that the lesioned rats had a decreased threshold compared to the control. Surprisingly, there was a significant positive correlation between mechanical threshold and survival rate of NBM cholinergic neurons. Furthermore, using local field potential (LFP) recordings and voltage-sensitive dye (VSD) imaging, we found that the forepaw-evoked response in the primary somatosensory cortex (S1) was significantly enhanced in both amplitude and spatial extent in the NBM-lesioned rats. The neurophysiological measures of S1 response, such as LFP amplitude and maximal activated cortical area depicted by VSD, were also correlated with withdrawal behavior. Additional pharmacological experiments demonstrated that forepaw-evoked responses were increased in naive rats by blocking S1 cholinergic receptors with mecamylamine and scopolamine, while the response decreased in NBM-lesioned rats with the cholinergic agonist carbachol. In addition, NBM burst stimulation, which facilitates acetylcholine release in the S1, suppressed subsequent sensory responses to forepaw stimulation. Taken together, these results suggest that neuronal loss in the NBM diminishes acetylcholine actions in the S1, thereby enhancing the cortical representation of sensory stimuli, which may in turn lead to behavioral hypersensitivity.
我们使用免疫毒素 192 免疫球蛋白 G-相思豆毒素在大鼠的 Meynert 基底核（NBM）中产生选择性胆碱能病变，并研究了 NBM 病变是否导致前爪触觉过敏。爪机械阈值测试表明，病变大鼠的阈值低于对照组。令人惊讶的是，机械阈值与 NBM 胆碱能神经元存活率之间存在显著正相关。此外，通过局部场电位（LFP）记录和电压敏感染料（VSD）成像，我们发现 NBM 病变大鼠的初级体感皮层（S1）中前爪诱发反应的幅度和空间范围均显著增强。S1 反应的神经生理测量，例如 LFP 幅度和 VSD 描绘的最大激活皮质面积，也与退缩行为相关。额外的药理学实验表明，用美金刚胺和东莨菪碱阻断 S1 胆碱能受体可增加未受损大鼠的前爪诱发反应，而 NBM 损伤大鼠的反应则因胆碱能激动剂卡巴胆碱而降低。此外，NBM 爆发刺激可促进 S1 中乙酰胆碱的释放，从而抑制随后对前爪刺激的感觉反应。总之，这些结果表明，NBM 中的神经元丧失会减弱 S1 中的乙酰胆碱作用，从而增强感觉刺激的皮质代表，这可能反过来导致行为过敏。
