PLC-beta 1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex

During development of the cerebral cortex, the invasion of thalamic axons a nd subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critic al signaling mechanism involving the activation of phospholipase C-beta1 (P LC-beta1) by metabotropic glutamate receptors (mGluRs). Homozygous null mut ation of either PLC-beta1 or mGluR5 dramatically disrupts the cytoarchitect ural differentiation of 'barrels' in the mouse somatosensory cortex, despit e 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-beta 1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical dif ferentiation can be genetically dissociated.