PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex.
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.
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
A J
AJ
Hannan
C
C
Blakemore
A
A
Katsnelson
T
T
Vitalis
K M
KM
Huber
M
M
Bear
J
J
Roder
D
D
Kim
H S
HS
Shin
P C
PC
Kind
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D054799:Phospholipase C beta; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013003:Somatosensory Cortex / Q000254:growth & development* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000172:deficiency* / Q000235:genetics
C578936:Grm5 protein, mouse; D007527:Isoenzymes; D018696:Neuroprotective Agents; D010716:Phosphatidylinositols; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse