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Neuropharmacology. 2013 Mar;66:143-50. doi: 10.1016/j.neuropharm.2012.03.010. Epub 2012 Mar 28.

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

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MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, BS8 1TD, United Kingdom.


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'.

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