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

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; Christopher I. Moore; Mark L. Andermann; Maria K. Lehtinen

doi:10.1016/j.neuron.2020.08.024

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

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, Christopher I. MooreMark L. Andermann, Maria K. Lehtinen

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

The choroid plexus is a vital brain barrier and source of cerebrospinal fluid. Using two-photon imaging of choroid plexus epithelium in live explants and in awake mice, Shipley et al. establish a platform for investigating subcellular calcium activity and secretion in epithelial cells and diverse surveillance behaviors in immune cells.

Original language	English
Pages (from-to)	623-639.e10
Journal	Neuron
Volume	108
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2020.08.024
State	Published - Nov 25 2020

Keywords

calcium activity
cerebrospinal fluid
choroid plexus
epithelial cells
immune cells
secretion
serotonin
two-photon imaging

Access to Document

10.1016/j.neuron.2020.08.024

Cite this

Shipley, F. B., Dani, N., Xu, H., Deister, C., Cui, J., Head, J. P., Sadegh, C., Fame, R. M., Shannon, M. L., Flores, V. I., Kishkovich, T., Jang, E., Klein, E. M., Goldey, G. J., He, K., Zhang, Y., Holtzman, M. J., Kirchhausen, T., Wyart, C., ... Lehtinen, M. K. (2020). Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface. Neuron, 108(4), 623-639.e10. https://doi.org/10.1016/j.neuron.2020.08.024

@article{ed0fa92f4fd24327838d91d2a25bb92f,

title = "Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface",

abstract = "The choroid plexus is a vital brain barrier and source of cerebrospinal fluid. Using two-photon imaging of choroid plexus epithelium in live explants and in awake mice, Shipley et al. establish a platform for investigating subcellular calcium activity and secretion in epithelial cells and diverse surveillance behaviors in immune cells.",

keywords = "calcium activity, cerebrospinal fluid, choroid plexus, epithelial cells, immune cells, secretion, serotonin, two-photon imaging",

author = "Shipley, {Frederick B.} and Neil Dani and Huixin Xu and Christopher Deister and Jin Cui and Head, {Joshua P.} and Cameron Sadegh and Fame, {Ryann M.} and Shannon, {Morgan L.} and Flores, {Vanessa I.} and Thomas Kishkovich and Emily Jang and Klein, {Eric M.} and Goldey, {Glenn J.} and Kangmin He and Yong Zhang and Holtzman, {Michael J.} and Tomas Kirchhausen and Claire Wyart and Moore, {Christopher I.} and Andermann, {Mark L.} and Lehtinen, {Maria K.}",

note = "Funding Information: We thank members of the Lehtinen, Andermann, and Moore labs for helpful discussions; A. Lutas, K. Fernando, S. Marsh, M. Webb, C. Chen, O. Alturkistani, and the IDDRC Imaging Core for advice and technical assistance; M. Bhaumik, BCH Genome Editing Core, and G. Marsischky for Htr2cmRuby3 design; M. Ericsson, HMS EM Facility; W.H. Fowle, NEU EM Facility; C. Wu at the BCH Viral Core; S. Gupton for VAMP3 expression vector; and J. Zhang for Z310 cells. This work was supported by a National Science Foundation (NSF) Graduate Research Fellowship (F.B.S.); a Glenn Foundation/American Federation for Aging Research (AFAR) Postdoctoral Fellowship and a Reagan Sloane Shanley Research Internship (N.D.); a William Randolph Hearst Fellowship (N.D. J.C.); NIH grant T32 HL110852 (J.C. R.M.F.); an Office of Faculty Development (OFD)/Basic/Translational Research Executive Committee (BTREC)/Clinical and Translational Research Executive Committee (CTREC) Faculty Development Fellowship Award (R.M.F.); NIH National Institute of Allergy and Infectious Diseases (NIAID) grant R01-AI130591 (T Kishkovich, K.H.); National Heart, Lung, and Blood Institute (NHLBI) grant R35-HL145242 (M.J.H.); GM075252 (T Kirchhausen); a gift from the Korn family and NSF Next Generation Networks for Neuroscience (NeuroNex) grant 1707352 (C.I.M.); the David Mahoney Neuroimaging Grant Program – Dana Foundation, NIH grants DP2 DK105570, DP1 AT010971, R01 DK109930, R21 EY03043-02, the McKnight Foundation, the Pew Foundation, the Smith Family Foundation, the Klarman Family Foundation, and the AFAR (M.L.A.); the Pediatric Hydrocephalus Foundation, a Tommy Fuss Center Innovation Grant, Simons Foundation Autism Research Initiative [SFARI] award 610670, a Harvard Brain Science Initiative Bipolar Disorder Seed Grant, and NIH grant R01 NS088566 (M.K.L.); Human Frontier Science Program grant RGP0063/2018 (C.W. M.K.L.); NIH grant RF1DA048790 (C.I.M. M.K.L.); New York Stem Cell Foundation (NYSCF) grants NYSCF-R-NI39 (C.W.) and NYSCF-R-NI38 (M.K.L.); and Boston Children's Hospital (BCH) Intellectual and Developmental Disabilities Research Center (IDDRC) grant 1U54HD090255. C.W. and M.K.L. are New York Stem Cell Foundation – Robertson Investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. F.B.S. N.D. M.L.A. C.I.M. and M.K.L. designed the study. N.D. and F.B.S. developed whole-tissue explants and imaging protocols. C.D. and M.L.A. developed the in vivo two-photon calcium imaging protocol. F.B.S. performed all computational analyses of all imaging data with advice from M.L.A. J.C. helped generate Htr2cmRuby3 mice. F.B.S. J.C. and M.L.S. analyzed peripheral activation of immune cells. H.X. analyzed secretory pathways and developed the vesicle imaging assay with assistance from C.W. K.H. and T. Kirchhausen. J.H. developed immediate-early gene assays. G.J.G. developed and T. Kishkovich, E.J. E.K. V.I.F. and C.S. refined the imaging cannula approach. J.C. and R.M.F. analyzed CSF cytokines. Y.Z. and M.J.H. shared FoxJ1-Cre mice. F.B.S. M.L.A. and M.K.L. wrote the manuscript. The authors declare no competing interests. Funding Information: We thank members of the Lehtinen, Andermann, and Moore labs for helpful discussions; A. Lutas, K. Fernando, S. Marsh, M. Webb, C. Chen, O. Alturkistani, and the IDDRC Imaging Core for advice and technical assistance; M. Bhaumik, BCH Genome Editing Core, and G. Marsischky for Htr2c mRuby3 design; M. Ericsson, HMS EM Facility; W.H. Fowle, NEU EM Facility; C. Wu at the BCH Viral Core; S. Gupton for VAMP3 expression vector; and J. Zhang for Z310 cells. This work was supported by a National Science Foundation (NSF) Graduate Research Fellowship (F.B.S.); a Glenn Foundation /American Federation for Aging Research (AFAR) Postdoctoral Fellowship and a Reagan Sloane Shanley Research Internship (N.D.); a William Randolph Hearst Fellowship (N.D., J.C.); NIH grant T32 HL110852 (J.C., R.M.F.); an Office of Faculty Development (OFD)/Basic/Translational Research Executive Committee (BTREC)/Clinical and Translational Research Executive Committee (CTREC) Faculty Development Fellowship Award (R.M.F.); NIH National Institute of Allergy and Infectious Diseases (NIAID) grant R01-AI130591 (T Kishkovich, K.H.); National Heart, Lung, and Blood Institute (NHLBI) grant R35-HL145242 (M.J.H.); GM075252 (T Kirchhausen); a gift from the Korn family and NSF Next Generation Networks for Neuroscience (NeuroNex) grant 1707352 (C.I.M.); the David Mahoney Neuroimaging Grant Program – Dana Foundation , NIH grants DP2 DK105570 , DP1 AT010971 , R01 DK109930 , R21 EY03043-02 , the McKnight Foundation , the Pew Foundation , the Smith Family Foundation , the Klarman Family Foundation , and the AFAR (M.L.A.); the Pediatric Hydrocephalus Foundation , a Tommy Fuss Center Innovation Grant, Simons Foundation Autism Research Initiative [SFARI] award 610670 , a Harvard Brain Science Initiative Bipolar Disorder Seed Grant, and NIH grant R01 NS088566 (M.K.L.); Human Frontier Science Program grant RGP0063/2018 (C.W., M.K.L.); NIH grant RF1DA048790 (C.I.M., M.K.L.); New York Stem Cell Foundation (NYSCF) grants NYSCF-R-NI39 (C.W.) and NYSCF-R-NI38 (M.K.L.); and Boston Children's Hospital (BCH) Intellectual and Developmental Disabilities Research Center (IDDRC) grant 1U54HD090255 . C.W. and M.K.L. are New York Stem Cell Foundation – Robertson Investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = nov,

day = "25",

doi = "10.1016/j.neuron.2020.08.024",

language = "English",

volume = "108",

pages = "623--639.e10",

journal = "Neuron",

issn = "0896-6273",

number = "4",

}

Shipley, FB, Dani, N, Xu, H, Deister, C, Cui, J, Head, JP, Sadegh, C, Fame, RM, Shannon, ML, Flores, VI, Kishkovich, T, Jang, E, Klein, EM, Goldey, GJ, He, K, Zhang, Y , Holtzman, MJ, Kirchhausen, T, Wyart, C, Moore, CI, Andermann, ML & Lehtinen, MK 2020, 'Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface', Neuron, vol. 108, no. 4, pp. 623-639.e10. https://doi.org/10.1016/j.neuron.2020.08.024

TY - JOUR

T1 - Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

AU - Shipley, Frederick B.

AU - Dani, Neil

AU - Xu, Huixin

AU - Deister, Christopher

AU - Cui, Jin

AU - Head, Joshua P.

AU - Sadegh, Cameron

AU - Fame, Ryann M.

AU - Shannon, Morgan L.

AU - Flores, Vanessa I.

AU - Kishkovich, Thomas

AU - Jang, Emily

AU - Klein, Eric M.

AU - Goldey, Glenn J.

AU - He, Kangmin

AU - Zhang, Yong

AU - Holtzman, Michael J.

AU - Kirchhausen, Tomas

AU - Wyart, Claire

AU - Moore, Christopher I.

AU - Andermann, Mark L.

AU - Lehtinen, Maria K.

N1 - Funding Information: We thank members of the Lehtinen, Andermann, and Moore labs for helpful discussions; A. Lutas, K. Fernando, S. Marsh, M. Webb, C. Chen, O. Alturkistani, and the IDDRC Imaging Core for advice and technical assistance; M. Bhaumik, BCH Genome Editing Core, and G. Marsischky for Htr2cmRuby3 design; M. Ericsson, HMS EM Facility; W.H. Fowle, NEU EM Facility; C. Wu at the BCH Viral Core; S. Gupton for VAMP3 expression vector; and J. Zhang for Z310 cells. This work was supported by a National Science Foundation (NSF) Graduate Research Fellowship (F.B.S.); a Glenn Foundation/American Federation for Aging Research (AFAR) Postdoctoral Fellowship and a Reagan Sloane Shanley Research Internship (N.D.); a William Randolph Hearst Fellowship (N.D. J.C.); NIH grant T32 HL110852 (J.C. R.M.F.); an Office of Faculty Development (OFD)/Basic/Translational Research Executive Committee (BTREC)/Clinical and Translational Research Executive Committee (CTREC) Faculty Development Fellowship Award (R.M.F.); NIH National Institute of Allergy and Infectious Diseases (NIAID) grant R01-AI130591 (T Kishkovich, K.H.); National Heart, Lung, and Blood Institute (NHLBI) grant R35-HL145242 (M.J.H.); GM075252 (T Kirchhausen); a gift from the Korn family and NSF Next Generation Networks for Neuroscience (NeuroNex) grant 1707352 (C.I.M.); the David Mahoney Neuroimaging Grant Program – Dana Foundation, NIH grants DP2 DK105570, DP1 AT010971, R01 DK109930, R21 EY03043-02, the McKnight Foundation, the Pew Foundation, the Smith Family Foundation, the Klarman Family Foundation, and the AFAR (M.L.A.); the Pediatric Hydrocephalus Foundation, a Tommy Fuss Center Innovation Grant, Simons Foundation Autism Research Initiative [SFARI] award 610670, a Harvard Brain Science Initiative Bipolar Disorder Seed Grant, and NIH grant R01 NS088566 (M.K.L.); Human Frontier Science Program grant RGP0063/2018 (C.W. M.K.L.); NIH grant RF1DA048790 (C.I.M. M.K.L.); New York Stem Cell Foundation (NYSCF) grants NYSCF-R-NI39 (C.W.) and NYSCF-R-NI38 (M.K.L.); and Boston Children's Hospital (BCH) Intellectual and Developmental Disabilities Research Center (IDDRC) grant 1U54HD090255. C.W. and M.K.L. are New York Stem Cell Foundation – Robertson Investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. F.B.S. N.D. M.L.A. C.I.M. and M.K.L. designed the study. N.D. and F.B.S. developed whole-tissue explants and imaging protocols. C.D. and M.L.A. developed the in vivo two-photon calcium imaging protocol. F.B.S. performed all computational analyses of all imaging data with advice from M.L.A. J.C. helped generate Htr2cmRuby3 mice. F.B.S. J.C. and M.L.S. analyzed peripheral activation of immune cells. H.X. analyzed secretory pathways and developed the vesicle imaging assay with assistance from C.W. K.H. and T. Kirchhausen. J.H. developed immediate-early gene assays. G.J.G. developed and T. Kishkovich, E.J. E.K. V.I.F. and C.S. refined the imaging cannula approach. J.C. and R.M.F. analyzed CSF cytokines. Y.Z. and M.J.H. shared FoxJ1-Cre mice. F.B.S. M.L.A. and M.K.L. wrote the manuscript. The authors declare no competing interests. Funding Information: We thank members of the Lehtinen, Andermann, and Moore labs for helpful discussions; A. Lutas, K. Fernando, S. Marsh, M. Webb, C. Chen, O. Alturkistani, and the IDDRC Imaging Core for advice and technical assistance; M. Bhaumik, BCH Genome Editing Core, and G. Marsischky for Htr2c mRuby3 design; M. Ericsson, HMS EM Facility; W.H. Fowle, NEU EM Facility; C. Wu at the BCH Viral Core; S. Gupton for VAMP3 expression vector; and J. Zhang for Z310 cells. This work was supported by a National Science Foundation (NSF) Graduate Research Fellowship (F.B.S.); a Glenn Foundation /American Federation for Aging Research (AFAR) Postdoctoral Fellowship and a Reagan Sloane Shanley Research Internship (N.D.); a William Randolph Hearst Fellowship (N.D., J.C.); NIH grant T32 HL110852 (J.C., R.M.F.); an Office of Faculty Development (OFD)/Basic/Translational Research Executive Committee (BTREC)/Clinical and Translational Research Executive Committee (CTREC) Faculty Development Fellowship Award (R.M.F.); NIH National Institute of Allergy and Infectious Diseases (NIAID) grant R01-AI130591 (T Kishkovich, K.H.); National Heart, Lung, and Blood Institute (NHLBI) grant R35-HL145242 (M.J.H.); GM075252 (T Kirchhausen); a gift from the Korn family and NSF Next Generation Networks for Neuroscience (NeuroNex) grant 1707352 (C.I.M.); the David Mahoney Neuroimaging Grant Program – Dana Foundation , NIH grants DP2 DK105570 , DP1 AT010971 , R01 DK109930 , R21 EY03043-02 , the McKnight Foundation , the Pew Foundation , the Smith Family Foundation , the Klarman Family Foundation , and the AFAR (M.L.A.); the Pediatric Hydrocephalus Foundation , a Tommy Fuss Center Innovation Grant, Simons Foundation Autism Research Initiative [SFARI] award 610670 , a Harvard Brain Science Initiative Bipolar Disorder Seed Grant, and NIH grant R01 NS088566 (M.K.L.); Human Frontier Science Program grant RGP0063/2018 (C.W., M.K.L.); NIH grant RF1DA048790 (C.I.M., M.K.L.); New York Stem Cell Foundation (NYSCF) grants NYSCF-R-NI39 (C.W.) and NYSCF-R-NI38 (M.K.L.); and Boston Children's Hospital (BCH) Intellectual and Developmental Disabilities Research Center (IDDRC) grant 1U54HD090255 . C.W. and M.K.L. are New York Stem Cell Foundation – Robertson Investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/11/25

Y1 - 2020/11/25

N2 - The choroid plexus is a vital brain barrier and source of cerebrospinal fluid. Using two-photon imaging of choroid plexus epithelium in live explants and in awake mice, Shipley et al. establish a platform for investigating subcellular calcium activity and secretion in epithelial cells and diverse surveillance behaviors in immune cells.

AB - The choroid plexus is a vital brain barrier and source of cerebrospinal fluid. Using two-photon imaging of choroid plexus epithelium in live explants and in awake mice, Shipley et al. establish a platform for investigating subcellular calcium activity and secretion in epithelial cells and diverse surveillance behaviors in immune cells.

KW - calcium activity

KW - cerebrospinal fluid

KW - choroid plexus

KW - epithelial cells

KW - immune cells

KW - secretion

KW - serotonin

KW - two-photon imaging

UR - http://www.scopus.com/inward/record.url?scp=85087440206&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2020.08.024

DO - 10.1016/j.neuron.2020.08.024

M3 - Article

C2 - 32961128

AN - SCOPUS:85087440206

SN - 0896-6273

VL - 108

SP - 623-639.e10

JO - Neuron

JF - Neuron

IS - 4

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this