The role of compartmentalized PKA signaling in hippocampal synaptic plasticity

Synaptic plasticity, the activity-dependent change in the strength of neuronal connections, is a proposed cellular mechanism of memory storage. Despite the fact that a neuron contains thousands of synapses, the expression of synaptic plasticity can be specific to subsets of synapses. This level of specificity is remarkable, because signal transduction pathways underlying synaptic plasticity involve diffusible second messenger molecules such as cAMP and proteins such as the catalytic subunit of PKA (cyclic-AMP dependent protein kinase). One way in which specificity can be achieved in a signal transduction system is by confining signaling molecules to subcellular domains. Spatial compartmentalization of PKA via binding to A-Kinase Anchoring Proteins (AKAPs) is a mechanism that contributes to the specificity of this signaling pathway in effecting downstream events. In the following chapters I will discuss the roles of PKA anchoring in neurons and highlight the functional roles of compartmentalizing PKA signals in hippocampal synaptic plasticity. Overall, compartmentalized PKA signaling is critically important for hippocampal synaptic plasticity and spatial memory. PKA anchoring is also required for the process of synaptic tagging and capture. Finally, AKAP12 is an AKAP that mediates compartmentalized signaling underlying hippocampal synaptic plasticity and spatial memory