Wu Feng-Ling, Chen Si-Hai, Li Jia-Ni, Zhao Liu-Jie, Wu Xue-Mei, Hong Jie, Zhu Ke-Hua, Sun Han-Xue, Shi Su-Juan, Mao E, Zang Wei-Dong, Cao Jing, Kou Zhen-Zhen, Li Yun-Qing
Department of Human Anatomy, College of Preclinical Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Department of Anatomy, Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China.
Metabolites. 2023 Feb 3;13(2):226. doi: 10.3390/metabo13020226.
Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIR-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIR-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIR-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIR-PVT pathway acts through GABAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.
未定带（ZI）是伤害性神经传递中的一个整合性丘脑底区域。先前的研究表明，吻侧未定带（ZIR）是丘脑室旁核（PVT）重要的γ-氨基丁酸能（GABA能）来源，但ZIR-PVT通路是否参与伤害性调制仍不清楚。因此，我们的研究采用解剖示踪、纤维光度测定、化学遗传学、光遗传学和局部药理学方法，来研究ZIR-PVT通路在小鼠伤害性神经传递中的作用。我们发现，从ZIR中的GABA能神经元到PVT的投射参与了伤害性神经传递。此外，ZIR-PVT通路的化学遗传学和光遗传学激活减轻了疼痛，而抑制ZIR-PVT回路的活动则诱导机械性超敏反应和部分热痛觉过敏。重要的是，体内药理学与光遗传学相结合表明，GABA-A受体（GABAR）对于从ZIR到PVT的GABA能抑制至关重要。我们的数据表明，ZIR-PVT通路通过PVT中表达GABAR的谷氨酸能神经元起作用，介导伤害性神经传递。
