Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

追踪脉络丛血液-脑脊液界面的钙动力学和免疫监视

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作者:Frederick B Shipley, Neil Dani, Huixin Xu, Christopher Deister, Jin Cui, Joshua P Head, Cameron Sadegh, Ryann M Fame, Morgan L Shannon, Vanessa I Flores, Thomas Kishkovich, Emily Jang, Eric M Klein, Glenn J Goldey, Kangmin He, Yong Zhang, Michael J Holtzman, Tomas Kirchhausen, Claire Wyart, Christop

Abstract

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.

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