PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex

Nat Neurosci. 2001 Mar;4(3):282-8. doi: 10.1038/85132.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / ultrastructure
  • Carbachol / pharmacology
  • Cell Differentiation / physiology*
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Glutamic Acid / metabolism*
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics
  • Mice
  • Mice, Knockout
  • Neuroprotective Agents / pharmacology
  • Phosphatidylinositols / metabolism
  • Phospholipase C beta
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / deficiency
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism
  • Somatosensory Cortex / growth & development*
  • Somatosensory Cortex / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Type C Phospholipases / deficiency*
  • Type C Phospholipases / genetics

Substances

  • Grm5 protein, mouse
  • Isoenzymes
  • Neuroprotective Agents
  • Phosphatidylinositols
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Receptors, Muscarinic
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Glutamic Acid
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Type C Phospholipases
  • Phospholipase C beta
  • Plcb1 protein, mouse