Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex

Isabella Panaccione, Rachel King, Gemma Molinaro, Barbara Riozzi, Giuseppe Battaglia, Ferdinando Nicoletti, Zafar I. Bashir*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

9 Citations (Scopus)

Abstract

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. PKM zeta is a kinase essential for the maintenance of LTP. We show for the first time that inhibition of PKM zeta 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 PKM zeta- 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'. (c) 2012 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalNeuropharmacology
Volume66
DOIs
Publication statusPublished - Mar 2013

Keywords

  • LTP
  • PKM zeta
  • Group I mGlu receptor
  • Cerebral cortex
  • Development
  • mTOR
  • Protein translation
  • LONG-TERM POTENTIATION
  • KINASE-M-ZETA
  • X MENTAL-RETARDATION
  • METABOTROPIC GLUTAMATE RECEPTORS
  • DENDRITIC ARBOR GROWTH
  • FMR1 KNOCKOUT MICE
  • PKM-ZETA
  • AMPA RECEPTORS
  • PLASTICITY
  • MEMORY

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