Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex.
Synaptic transmission is essential for early development of the central nervous system. However, the mechanisms that regulate early synaptic transmission in the cerebral cortex are unclear. PKMζ is a kinase essential for the maintenance of LTP. We show for the first time that inhibition of PKMζ produces a profound depression of basal synaptic transmission in neonatal, but not adult, rat perirhinal cortex. This suggests that synapses in early development are in a constitutive LTP-like state. Furthermore, basal synaptic transmission in immature, but not mature, perirhinal cortex relies on persistent activity of metabotropic glutamate (mGlu) receptor, PI3Kinase and mammalian target of rapamycin (mTOR). Thus early in development, cortical synapses exist in an LTP-like state maintained by tonically active mGlu receptor-, mTOR- and PKMζ- dependent cascades. These results provide new understanding of the molecular mechanisms that control synapses during development and may aid our understanding of developmental disorders such as autism and schizophrenia. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, BS8 1TD, United Kingdom.
Isabella
I
Panaccione
Rachel
R
King
Gemma
G
Molinaro
Barbara
B
Riozzi
Giuseppe
G
Battaglia
Ferdinando
F
Nicoletti
Zafar I
ZI
Bashir
D000818:Animals; D000831:Animals, Newborn; D017774:Long-Term Potentiation / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D013702:Temporal Lobe / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D000099221:Protein Kinase C zeta
D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D018094:Receptors, Metabotropic Glutamate; D058570:TOR Serine-Threonine Kinases; D000099221:Protein Kinase C zeta; C546845:mTOR protein, rat