The molecular composition of the postsynaptic membrane is sculpted by
synaptic activity. During synaptic plasticity at excitatory synapses, numerous
structural, signaling and receptor molecules concentrate at the postsynaptic
density (PSD) to regulate synaptic strength. We developed an approach that uses
light to tune the abundance of specific molecules in the PSD. We used this
approach to investigate the relationship between the number of AMPA-type
glutamate receptors in the PSD and synaptic strength. Surprisingly, adding more
AMPA receptors to excitatory contacts had little effect on synaptic strength.
Instead, we observed increased excitatory input through the apparent addition of
new functional sites. Our data support a model where adding AMPA receptors is
sufficient to activate synapses that had few receptors to begin with, but that
additional remodeling events are required to strengthen established synapses.
More broadly, this approach introduces the precise spatiotemporal control of
optogenetics to molecular control of synaptic function.