Activity regulated AMPA receptor trafficking in retina
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At highly plastic synapses of hippocampus and cortex, the AMPA-type glutamate receptors (AMPARs) cycle rapidly into and out of the synaptic membrane. The dynamic expression of AMPAR maintains stable basal glutamatergic transmission, and has been proposed to be necessary for the expression of long-term plasticity. However, it is not clear whether the rapid AMPAR cycling is a unique property underlying the potentiation or depression of synaptic transmission in hippocampus and cortex; or if cycling is also expressed in other excitatory synapses, especially in the areas not known to exhibit long-term plasticity. We have identified the rapid retinal AMPAR cycling in the absence of excitatory synaptic activity, indicating that cycling may be expressed in functionally disparate neurons. Furthermore, existence of rapid cycling drives the questioning in the possible synaptic plasticity in retina.;The synaptic activation promotes the rate and extent of AMPAR cycling. In retina, the tonic and excessive glutamate release brings up a special challenge in the stable synaptic transmission. A question remains about the regulation of AMPAR cycling under such unique synaptic activity pattern. In contrast to hippocampus and cortex, light-evoked activity stabilizes AMPARs in ON ganglion cells. As little as 8 hours dark adaptation is sufficient to trigger a switch of cycling modes, opening up the possibility in the physiological occurrence of AMPAR cycling during light/dark cycle.;Most significantly, we find that the induction of cycling during light adaptation is accompanied by a decrease in the composition of synaptic GluR2-containing AMPARs. A previously unknown form of plasticity has been first identified at this synapse, in which light may modulate the calcium permeability of synaptic AMPARs. Furthermore, in the dark-adapted retinal neurons, AMPARs are sequestered from the synapses by the regulatory proteins that interact with the GluR2/3 subunits. In suppression of the light-evoked synaptic activity, cycling may thereby remove GluR2-containing receptors from the synapses, and modify the retinal synaptic AMPARs expression.;In conclusion, the dynamic expression of AMPARs in retina demonstrates its potential for the light-modulated synaptic plasticity. Under distinct light states, the variation in the AMPAR composition significantly modulates the calcium signaling of retinal neurons.
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