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-beta1 (PLC-beta1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-beta1 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-beta1-/- mice during barrel development. Our data indicate that PLC-beta1 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / metabolism
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Axons / ultrastructure
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Carbachol / pharmacology
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Cell Differentiation / physiology*
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Cycloleucine / analogs & derivatives*
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Cycloleucine / pharmacology
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Glutamic Acid / metabolism*
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Inositol 1,4,5-Trisphosphate / metabolism
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Isoenzymes / deficiency*
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Isoenzymes / genetics
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Mice
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Mice, Knockout
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Neuroprotective Agents / pharmacology
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Phosphatidylinositols / metabolism
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Phospholipase C beta
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / deficiency
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Receptors, Metabotropic Glutamate / drug effects
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Receptors, Metabotropic Glutamate / genetics
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Receptors, Metabotropic Glutamate / metabolism*
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / metabolism
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Somatosensory Cortex / growth & development*
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Somatosensory Cortex / metabolism*
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Synaptic Transmission / physiology*
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Type C Phospholipases / deficiency*
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Type C Phospholipases / genetics
Substances
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Grm5 protein, mouse
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Isoenzymes
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Neuroprotective Agents
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Phosphatidylinositols
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Receptors, Muscarinic
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Cycloleucine
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1-amino-1,3-dicarboxycyclopentane
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Glutamic Acid
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Inositol 1,4,5-Trisphosphate
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Carbachol
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Type C Phospholipases
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Phospholipase C beta
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Plcb1 protein, mouse