Johnson Caroline S, Bains Jaideep S, Watts Alan G
The Department of Biological Sciences, USC Dornsife College of Letters, Arts, and Sciences, and Neuroscience, Graduate Program, University of Southern California, Los Angeles, California.
Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada.
J Comp Neurol. 2018 Jun 1;526(8):1287-1306. doi: 10.1002/cne.24407. Epub 2018 Mar 2.
Virtually all rodent neuroendocrine corticotropin-releasing-hormone (CRH) neurons are in the dorsal medial parvicellular (mpd) part of the paraventricular nucleus of the hypothalamus (PVH). They form the final common pathway for adrenocortical stress responses. Their activity is controlled by sets of GABA-, glutamate-, and catecholamine-containing inputs arranged in an interactive pre-motor network. Defining the nature and arrangement of these inputs can help clarify how stressor type and intensity information is conveyed to neuroendocrine neurons. Here we use immunohistochemistry with high-resolution 3-dimensional image analyses to examine the arrangement of single- and co-occurring GABA, glutamate, and catecholamine markers in synaptophysin-defined pre-synaptic terminals in the PVHmpd of unstressed rats and Crh-IRES-Cre;Ai14 transgenic mice: respectively, vesicular glutamate transporter 2 (VGluT2), vesicular GABA transporter (VGAT), dopamine β-hydroxylase (DBH), and phenylethanolamine n-methyltransferase (PNMT). Just over half of all PVHmpd pre-synaptic terminals contain VGAT, with slightly less containing VGluT2. The vast majority of terminal appositions with mouse CRH neurons occur non-somatically. However, there are significantly more somatic VGAT than VGluT2 appositions. In the rat PVHmpd, about five times as many pre-synaptic terminals contain PNMT than DBH only. However, because epinephrine release has never been detected in the PVH, PNMT terminals may functionally be noradrenergic not adrenergic. PNMT and VGluT2 co-occur in some pre-synaptic terminals indicating the potential for co-transmission of glutamate and norepinephrine. Collectively, these results provide a structural basis for how GABA/glutamate/catecholamine interactions enable adrenocortical responses to fast-onset interosensory stimuli, and more broadly, how combinations of PVH neurotransmitters and neuromodulators interact dynamically to control adrenocortical activity.
几乎所有啮齿动物的神经内分泌促肾上腺皮质激素释放激素（CRH）神经元都位于下丘脑室旁核（PVH）的背内侧小细胞（mpd）部分。它们构成了肾上腺皮质应激反应的最终共同通路。它们的活动受一组排列在交互式运动前网络中的含γ-氨基丁酸（GABA）、谷氨酸和儿茶酚胺的输入信号控制。明确这些输入信号的性质和排列有助于阐明应激源类型和强度信息是如何传递给神经内分泌神经元的。在这里，我们使用免疫组织化学结合高分辨率三维图像分析，来检查未应激大鼠和Crh-IRES-Cre;Ai14转基因小鼠PVHmpd中，在突触素定义的突触前终末中单一和共现的GABA、谷氨酸和儿茶酚胺标志物的排列情况，这些标志物分别是囊泡谷氨酸转运体2（VGluT2）、囊泡GABA转运体（VGAT）、多巴胺β-羟化酶（DBH）和苯乙醇胺N-甲基转移酶（PNMT）。所有PVHmpd突触前终末中略超过一半含有VGAT，含有VGluT2的略少。绝大多数与小鼠CRH神经元的终末并置并非发生在胞体上。然而，与胞体并置的VGAT明显多于VGluT2。在大鼠PVHmpd中，仅含PNMT的突触前终末数量约为仅含DBH的五倍。然而，由于在PVH中从未检测到肾上腺素释放，PNMT终末在功能上可能是去甲肾上腺素能的而非肾上腺素能的。PNMT和VGluT2在一些突触前终末中共存，表明谷氨酸和去甲肾上腺素可能共同传递。总的来说，这些结果为GABA/谷氨酸/儿茶酚胺相互作用如何使肾上腺皮质对快速发作的内感受刺激产生反应，以及更广泛地说，PVH神经递质和神经调质的组合如何动态相互作用以控制肾上腺皮质活动提供了结构基础。
