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Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal
Isabella Panaccione1, Rachel King, Gemma Molinaro
1MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, BS8 1TD, United Kingdom.
Neuropharmacology
|January 30, 2013
Summary
Early brain synapses maintain a potent state via protein kinase M zeta (PKMζ) and metabotropic glutamate receptors. This developmental mechanism, crucial for central nervous system formation, differs significantly from adult synaptic regulation.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Synaptic transmission is critical for central nervous system development.
- Mechanisms regulating early cortical synaptic transmission remain largely unknown.
- Protein kinase M zeta (PKMζ) is vital for long-term potentiation (LTP) maintenance.
Purpose of the Study:
- To investigate the role of PKMζ in early synaptic transmission in the rat perirhinal cortex.
- To elucidate the molecular pathways regulating basal synaptic transmission during development.
- To understand the differences in synaptic regulation between neonatal and adult brains.
Main Methods:
- Inhibition of PKMζ in neonatal and adult rat perirhinal cortex.
- Assessment of basal synaptic transmission.
- Investigation of metabotropic glutamate (mGlu) receptor, PI3Kinase, and mammalian target of rapamycin (mTOR) pathway involvement.
Main Results:
- PKMζ inhibition profoundly depressed basal synaptic transmission in neonatal, but not adult, perirhinal cortex.
- Immature perirhinal cortex synapses depend on persistent activity of mGlu receptors, PI3Kinase, and mTOR.
- Neonatal cortical synapses appear to exist in a constitutive LTP-like state.
Conclusions:
- Early cortical synapses are maintained in an LTP-like state by PKMζ, mGlu receptor, PI3Kinase, and mTOR-dependent cascades.
- This developmental regulation of synaptic transmission differs from adult mechanisms.
- Findings offer insights into developmental disorders like autism and schizophrenia.
