Shao Yu-Feng, Wang Can, Rao Xiao-Ping, Wang Hua-Dong, Ren Yan-Li, Li Jing, Dong Chao-Yu, Xie Jun-Fan, Yang Xing-Wen, Xu Fu-Qiang, Hou Yi-Ping
Departments of Neuroscience, Anatomy, Histology, and Embryology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Key Lab of Neurology of Gansu Province, Lanzhou University, Lanzhou, China.
Front Mol Neurosci. 2021 Dec 24;14:752516. doi: 10.3389/fnmol.2021.752516. eCollection 2021.
Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1-1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.
神经肽 S(NPS)通过激活其同源受体(NPSR)发挥作用。NPSR 在杏仁核后内侧高水平表达,提示 NPS-NPSR 系统应参与社会信息素诱导的社会行为调节。本研究旨在探讨中枢给予 NPS 或 NPSR 拮抗剂对小鼠警报信息素(AP)诱发的防御和风险评估行为的影响。此外,还采用新型高亮度顺行多突触病毒 H129-H8、c-Fos 和 NPSR 免疫染色来揭示 NPS 作用的相关神经回路和靶点。暴露于 AP 的小鼠防御和风险评估行为增强。脑室内(i.c.v.)注射 NPS(0.1 - 1 nmol)显著减弱了 AP 诱发的防御和风险评估行为。40 nmol 剂量的 NPSR 拮抗剂[D-Val]NPS 完全阻断了 0.5 nmol NPS(该剂量在剂量范围内效果最佳)的作用。在单侧嗅球(OB)注射病毒 72 小时后,在双侧杏仁核后内侧(MePD)和杏仁核后腹侧(MePV)观察到 H129-H8 标记的神经元,提示 MePD 和 MePV 接收来自 OB 的嗅觉信息输入。在 MePD 和 MePV 中,同时表达 NPSR 的 H129-H8 标记神经元的百分比分别为 90.27 ± 3.56%和 91.67 ± 2.46%。NPS(0.5 nmol,i.c.v.)显著增加了 MePD 和 MePV 中 Fos 免疫反应性(-ir)神经元的数量,并且大多数 NPS 诱导的 Fos-ir 神经元也表达 NPSR。在较低剂量下,在 MePD/MePV 局部注射能更好地重现 NPS 或[D-Val]NPS 的行为特征。本研究结果表明,NPS 通过选择性激活杏仁核后内侧携带 NPSR 的神经元,减弱了小鼠中 AP 诱发的防御和风险评估行为。