Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
Neuron. 2020 Nov 25;108(4):623-639.e10. doi: 10.1016/j.neuron.2020.08.024. Epub 2020 Sep 21.
The choroid plexus (ChP) epithelium is a source of secreted signaling factors in cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we develop imaging tools to interrogate these functions in adult lateral ventricle ChP in whole-mount explants and in awake mice. By imaging epithelial cells in intact ChP explants, we observed calcium activity and secretory events that increased in frequency following delivery of serotonergic agonists. Using chronic two-photon imaging in awake mice, we observed spontaneous subcellular calcium events as well as strong agonist-evoked calcium activation and cytoplasmic secretion into CSF. Three-dimensional imaging of motility and mobility of multiple types of ChP immune cells at baseline and following immune challenge or focal injury revealed a range of surveillance and defensive behaviors. Together, these tools should help illuminate the diverse functions of this understudied body-brain interface.
脉络丛(ChP)上皮是脑脊液(CSF)中分泌信号因子的来源,也是血液和大脑之间的关键屏障。在这里,我们开发了成像工具来研究成年侧脑室 ChP 中的这些功能,包括整体培养物和清醒小鼠。通过对完整 ChP 培养物中上皮细胞的成像,我们观察到钙活性和分泌事件的频率增加,随后给予 5-羟色胺能激动剂。使用清醒小鼠的慢性双光子成像,我们观察到自发的亚细胞钙事件,以及强烈的激动剂诱导的钙激活和细胞质分泌到 CSF 中。在基线和免疫挑战或局灶性损伤后,对多种类型 ChP 免疫细胞的运动和迁移进行三维成像,揭示了一系列监视和防御行为。总之,这些工具应该有助于阐明这个研究较少的身体-大脑界面的多种功能。