Organizing signal transduction in the postsynaptic density

Excitatory neurons in the CNS receive thousands of synaptic contacts from other excitatory neurons. An increase in the strength of a relatively small number of these synapses can store a memory by binding connected neurons into a circuit in which all of the neurons fire each time the specific memory is evoked. An increase in synaptic strength involves addition of new glutamate receptors to the synaptic membrane, and re-arrangement of the cytoskeleton to support a larger synapse. Biochemical signaling enzymes that control this process, which is called “activity-dependent synaptic plasticity,” are organized near the postsynaptic membrane. The enzymes include several protein kinases, adenylyl cyclase, and regulators of Ras and Rap. Many of them are attached to a multiprotein scaffold called the “postsynaptic density.” At least five classes of scaffold proteins contribute to the precise orchestration of changes in synaptic strength: PSD-95 and other MAGUKS, SHANKs, Homer, AKAPs, and Densin. What we have learned thus far about the dynamic properties of the postsynaptic density reveals new ways to rapidly regulate the number and sensitivity of membrane receptors