We have recently shown that two forms of synaptic plasticity that involve accumulation of AMPA receptors at synapses, synaptic scaling and long term potentiation (LTP), are molecularly distinct (Gainey et al., 2009). We knocked down the AMPA receptor subunit GluR2 in cultured cortical neurons for 2 days with an shRNA and showed that the expression of synaptic scaling but not LTP requires the GluR2 subunit. We can rescue synaptic scaling by co-expression of GluR2 that is resistant to the shRNA.

A chimeric GluR2 subunit that has a GluR1 C-tail domain does not rescue scaling, suggesting that the C-tail domain is required for the expression of scaling. The C-tail domain is known to bind various trafficking proteins and is important for the proper trafficking of GluR2-containing AMPARs to the synaptic membrane. Ongoing experiments will determine which interactions between GluR2 and trafficking proteins are required for synaptic scaling.
Synaptic Scaling and GluR2 Signaling
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Gainey et al., 2009.
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