Yao Yifan, Chen Yannan, Tomer Raju, Silver Rae
Department of Psychology, Columbia University, New York, New York, USA.
Department of Biological Sciences, Columbia University, New York, New York, USA.
J Neuroendocrinol. 2025 Apr;37(4):e13490. doi: 10.1111/jne.13490. Epub 2025 Jan 7.
Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins. Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland. The second was discovered a few years ago and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu. They line the surface of brain ventricles and bear fenestrated capillaries thereby lacking blood-brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light-sheet microscopy to acquire volumetric images of blood vessels and traced the vasculature in two experiments. In the first, the whole brain vasculature was registered to the Allen Brain Atlas in order to identify the nuclei to which the SFO and AP are attached. In the second study, regionally specified immunolabeling was used to identify the attachment sites and vascular connections between the AP, and the SFO to their respective parenchymal attachment sites. There are venous portal pathways linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the arrangement of portal vessels, the AP and the nucleus of the solitary tract share a common capillary bed. Taken together, the results reveal that all three sensory CVOs bear direct capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.
可扩散信号的贡献者包括通过连接静脉连接两个毛细血管床的门脉系统。门脉系统允许可扩散信号以高浓度直接从一个毛细血管床运输到另一个毛细血管床，而不会在体循环中被稀释。在大脑中已发现两个门脉系统。第一个门脉系统是在近一个世纪前发现的，它将正中隆起与垂体前叶相连。第二个门脉系统是几年前发现的，它将视交叉上核与终板血管器相连，终板血管器是一个感觉性室周器官（CVO）。感觉性CVO带有神经元受体，用于感知液体环境中的信号。它们排列在脑室表面，具有有孔毛细血管，因此缺乏血脑屏障。尚不清楚其他感觉性CVO，即穹窿下器官（SFO）和最后区（AP）是否与附近的实质组织形成门脉神经血管连接。为了保持CVO及其相邻神经纤维的脉管系统完整性，我们结合了iDISCO清除法和光片显微镜技术，以获取血管的体积图像，并在两个实验中追踪脉管系统。在第一个实验中，将全脑脉管系统与艾伦脑图谱进行配准，以识别SFO和AP所附着的核团。在第二项研究中，使用区域特异性免疫标记来识别AP和SFO与其各自实质附着部位之间的附着位点和血管连接。存在连接SFO毛细血管和后隔核（即隔纤维核和隔三角核）的静脉门脉途径。与门脉血管的排列不同，AP和孤束核共享一个共同的毛细血管床。综上所述，结果表明所有三个感觉性CVO都与相邻的神经纤维有直接的毛细血管连接，为可扩散信号从其来源传播到目标提供了一条直接途径。
