PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex

Anthony J. Hannan; Colin Blakemore; Alla Katsnelson; Tania Vitalis; Kimberly M. Huber; Mark Bear; John Roder; Daesoo Kim; Hee Sup Shin; Peter C. Kind

doi:10.1038/85132

PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex

Anthony J. Hannan, Colin Blakemore, Alla Katsnelson, Tania Vitalis, Kimberly M. Huber, Mark Bear, John Roder, Daesoo Kim, Hee Sup Shin, Peter C. Kind

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

187 Scopus citations

Abstract

During development of the cerebral cortex, the invasion of thalamic axons and subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critical signaling mechanism involving the activation of phospholipase C-β1 (PLC-β1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-β1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of 'barrels' in the mouse somatosensory cortex, despite segregation in the pattern of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide hydrolysis is dramatically reduced in PLC-β1^-/- mice during barrel development. Our data indicate that PLC-β1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical differentiation can be genetically dissociated.

Original language	English (US)
Pages (from-to)	282-288
Number of pages	7
Journal	Nature neuroscience
Volume	4
Issue number	3
DOIs	https://doi.org/10.1038/85132
State	Published - 2001

ASJC Scopus subject areas

General Neuroscience

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title = "PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex",

abstract = "During development of the cerebral cortex, the invasion of thalamic axons and subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critical signaling mechanism involving the activation of phospholipase C-β1 (PLC-β1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-β1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of 'barrels' in the mouse somatosensory cortex, despite segregation in the pattern of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide hydrolysis is dramatically reduced in PLC-β1-/- mice during barrel development. Our data indicate that PLC-β1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical differentiation can be genetically dissociated.",

author = "Hannan, {Anthony J.} and Colin Blakemore and Alla Katsnelson and Tania Vitalis and Huber, {Kimberly M.} and Mark Bear and John Roder and Daesoo Kim and Shin, {Hee Sup} and Kind, {Peter C.}",

note = "Funding Information: This work was supported by the Medical Research Council (C.B.), the Wellcome Trust (P.K., C.B.) the Nuffield Medical Trust (A.H.), Oxford McDonnell-Pew Centre for Cognitive Neuroscience and a Creative Research Initiative Program from the Korean Government (H.S.). We thank T. Andrews, A. van Dellen, Z. Molnar, D. Moore and C. Hannan for discussions and comments on earlier versions of the manuscript, and M. O{\textquoteright}Brien and P. Cordery for technical assistance.",

year = "2001",

doi = "10.1038/85132",

language = "English (US)",

volume = "4",

pages = "282--288",

journal = "Nature neuroscience",

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AU - Hannan, Anthony J.

AU - Blakemore, Colin

AU - Katsnelson, Alla

AU - Vitalis, Tania

AU - Huber, Kimberly M.

AU - Bear, Mark

AU - Roder, John

AU - Kim, Daesoo

AU - Shin, Hee Sup

AU - Kind, Peter C.

N1 - Funding Information: This work was supported by the Medical Research Council (C.B.), the Wellcome Trust (P.K., C.B.) the Nuffield Medical Trust (A.H.), Oxford McDonnell-Pew Centre for Cognitive Neuroscience and a Creative Research Initiative Program from the Korean Government (H.S.). We thank T. Andrews, A. van Dellen, Z. Molnar, D. Moore and C. Hannan for discussions and comments on earlier versions of the manuscript, and M. O’Brien and P. Cordery for technical assistance.

PY - 2001

Y1 - 2001

N2 - During development of the cerebral cortex, the invasion of thalamic axons and subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critical signaling mechanism involving the activation of phospholipase C-β1 (PLC-β1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-β1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of 'barrels' in the mouse somatosensory cortex, despite segregation in the pattern of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide hydrolysis is dramatically reduced in PLC-β1-/- mice during barrel development. Our data indicate that PLC-β1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical differentiation can be genetically dissociated.

AB - During development of the cerebral cortex, the invasion of thalamic axons and subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critical signaling mechanism involving the activation of phospholipase C-β1 (PLC-β1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-β1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of 'barrels' in the mouse somatosensory cortex, despite segregation in the pattern of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide hydrolysis is dramatically reduced in PLC-β1-/- mice during barrel development. Our data indicate that PLC-β1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical differentiation can be genetically dissociated.

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PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex

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