Genetic manipulations of AMPA glutamate receptors in hippocampal synaptic plasticity.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the principal mediators of fast excitatory synaptic transmission and they are required for various forms of synaptic plasticity, including long-term potentiation (LTP) and depression (LTD), which are key mechanisms of learning and memory. AMPARs are tetrameric complexes assembled from four subunits (GluA1-4), however, the lack of subunit-specific pharmacological tools has made the assessment of individual subunits difficult. The application of genetic techniques, particularly gene targeting, allows for precise manipulation and dissection of each subunit in the regulation of neuronal function and behaviour. In this review, we summarize studies using various mouse models with genetically altered AMPARs and focus on their roles in basal synaptic transmission, LTP, and LTD at the hippocampal CA1 synapse. These studies provide strong evidence that there are multiple forms of LTP and LTD at this synapse which can be induced by various induction protocols, and they are differentially regulated by different AMPAR subunits and domains. We conclude that it is necessary to delineate the mechanism of each of these forms of plasticity and their contribution to memory and brain disorders.