Activity-dependent synaptic plasticity in retinal ganglion cells

Abstract

At many excitatory synapses, AMPA-type receptors (AMPARs) are not statically situated in the membrane, but undergo continuous rounds of endocytosis and exocytosis, referred to as rapid cycling. AMPAR cycling is believed to play a role in certain forms of synaptic plasticity, but the link between cycling and synaptic function is not well understood. We have previously demonstrated that AMPARs cycle in neurons of the inner retina, including amacrine and ganglion cells, and that cycling is inhibited by synaptic activity. Recording from cultured neurons and ON ganglion cells in the flat-mount retina, we now show that rapid cycling is primarily, perhaps exclusively, restricted to AMPARs that contain the GluR2 subunit, and that cycle is confined to extrasynaptic receptors. We also demonstrate a form of plasticity at the ON bipolar cell - ON ganglion cell synapse, whereby synaptic quiescence drives a change in the composition of AMPARs from predominantly GluR2-containing to GluR2-lacking. Finally, we provide evidence linking synaptic receptor composition and cycling, showing that disruption of cycling leads increases the number of GluR2-containing receptors in the ON bipolar - ON ganglion cell synapse. We propose that cycling lowers the number of GluR2-containing receptors at the surface and, consequently, within the synapse. After increased levels of synaptic activity, cycling ceases, and all GluR2-containing receptors are free to go to the surface, where they can be delivered to synapses. Our results suggest that by regulating the cycling of AMPARs, ambient light can modulate the composition of synaptic receptors in ON ganglion cells. Copyright © 2007 Society for Neuroscience.