AMPA Receptor Phosphorylation in Synaptic Plasticity: Insights from Knockin Mice

Excerpt

Synaptic plasticity in the brain has been implicated to play a role in major brain functions, including learning and memory, developmental plasticity, recovery after injury and drug addiction. The current understanding of the mechanisms of synaptic plasticity derives from molecular and cellular analysis of long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are readily elicited from many brain regions with different induction and expression mechanisms. At least two different induction mechanisms for LTP and LTD exist, one that depends on activation of N-methyl-D-aspartate (NMDA) receptors and another that does not. The expression of NMDA receptor-dependent and receptor-independent LTP and LTD seem to have overlapping but different signalling mechanisms [1]. Most of the molecular details on NMDA receptor-dependent LTP and LTD have come from studies in the CA1 region of the hippocampus. At least in this region of the brain, regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors seems to underlie post-synaptic changes associated with NMDA receptor-dependent LTP and LTD. Especially, evidence exists that changes in AMPA receptor phosphorylation is one of the mechanisms critical for the expression of NMDA receptor-dependent bidirectional synaptic plasticity.

This review will summarize the recent findings from our work using gene “knockin” mice lacking specific phosphorylation sites on the GluR1 subunit of AMPA receptors, and discuss the implications of our results that elucidate the basic mechanisms of NMDA receptor-dependent synaptic plasticity.