Abstract
NMDARs (N-methyl-D-aspartate receptors) are critical for synaptic function throughout the CNS (central nervous system). NMDAR-mediated Ca2+ in.ux is implicated in neuronal differentiation, neuronal migration, synaptogenesis, structural remodelling, long-lasting forms of synaptic plasticity and higher cognitive functions. NMDAR-mediated Ca2+ signalling in dendritic spines is not static, but can be remodelled in a cell- and synapse-specific manner by NMDAR subunit composition, protein kinases and neuronal activity during development and in response to sensory experience. Recent evidence indicates that Ca2+ permeability of neuronal NMDARs, NMDAR-mediated Ca2+ signalling in spines and induction of NMDAR-dependent LTP (long-term potentiation) at hippocampal Schaffer collateral-CA1 synapses are under control of the cAMP/PKA (protein kinase A) signalling cascade. Thus, by enhancing Ca2+ influx through NMDARs in spines, PKA can regulate the induction of LTP. An emerging concept is that activity-dependent regulation of NMDAR-mediated Ca2+ signalling by PKA and by extracellular signals that modulate cAMP or protein phosphatases at synaptic sites provides a dynamic and potentially powerful mechanism for bi-directional regulation of synaptic efficacy and remodelling.
Original language | English (US) |
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Pages (from-to) | 1369-1374 |
Number of pages | 6 |
Journal | Biochemical Society transactions |
Volume | 37 |
Issue number | 6 |
DOIs | |
State | Published - 2009 |
Keywords
- Calcium
- N-methyl-d-aspartate receptor (NMDAR)
- Protein kinase
- Signalling
- Synaptic plasticity
ASJC Scopus subject areas
- Biochemistry