TY - JOUR
T1 - Constitutively active group i mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex
AU - Panaccione, Isabella
AU - King, Rachel
AU - Molinaro, Gemma
AU - Riozzi, Barbara
AU - Battaglia, Giuseppe
AU - Nicoletti, Ferdinando
AU - Bashir, Zafar I.
PY - 2013/3
Y1 - 2013/3
N2 - 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'.
AB - 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'.
KW - Cerebral cortex
KW - Development
KW - Group I mGlu receptor
KW - LTP
KW - mTOR
KW - PKMζ
KW - Protein translation
UR - http://www.scopus.com/inward/record.url?scp=84872144037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872144037&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2012.03.010
DO - 10.1016/j.neuropharm.2012.03.010
M3 - Article
C2 - 23357951
AN - SCOPUS:84872144037
VL - 66
SP - 143
EP - 150
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
ER -