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

Neuron. 2020 Nov 25;108(4):623-639.e10. doi: 10.1016/j.neuron.2020.08.024. Epub 2020 Sep 21.

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.

Keywords: calcium activity; cerebrospinal fluid; choroid plexus; epithelial cells; immune cells; secretion; serotonin; two-photon imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cerebrospinal Fluid / immunology*
  • Cerebrospinal Fluid / metabolism*
  • Choroid Plexus / drug effects
  • Choroid Plexus / immunology*
  • Choroid Plexus / metabolism*
  • Epithelium / metabolism
  • Mice
  • Optical Imaging / methods*
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Serotonin Receptor Agonists
  • Calcium