Summary During development neurons are constantly refining their connections in response to changes in activity. Experience-dependent plasticity is a key form of synaptic plasticity, involving changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) accumulation at synapses. Here we report a critical role for the AMPAR auxiliary subunit, stargazin, in this plasticity. We show that stargazin is functional at the retinogeniculate synapse and that in the absence of stargazin, the refinement of the retinogeniculate synapse is specifically disrupted during the experience-dependent phase. Importantly, we found that stargazin expression and phosphorylation increased with visual deprivation, and led to reduced AMPAR rectification at the retinogeniculate synapse. To test whether stargazin may play a role in homeostatic plasticity, we turned to cultured neurons and found that stargazin phosphorylation is essential for synaptic scaling. Overall, our data reveal an important new role of stargazin in regulating AMPAR abundance and composition at glutamatergic synapses during homeostatic and experience-dependent plasticity.
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