PKA Anchoring and Synaptic Tagging and Capture

Synaptic tagging and capture (STC) hypothesis has been receiving increasing attention because it reflects the heterosynaptic association of information processing during memory formation in the brain. Indeed, electrophysiological and behavioral studies suggest that STC is a better cellular model for memory formation than the conventional homosynaptic experiment. In STC, a short-lasting potentiation in one pathway becomes persistent when it is paired with a long-lasting potentiation in the other independent pathway. It has been proposed that the setting of a synapse-specific tag and the capture of nonsynapse-specific diffusible gene products by the tag determines the fate of each pathway. However, the mechanism of STC is still elusive and three major questions should be answered: 1. What is the tag and how does it modulate synapse-specific plasticity? 2. How does the tag capture gene products? 3. What are the gene products and how are they produced? Although several molecules and processes have been suggested to answer these questions, they only provide partial explanations about the phenomenon. Here, this chapter will discuss how PKA modulates synapse-specific neuronal activity by coordinating signaling molecules and processes through PKA anchoring proteins, and how anchored PKA is involved in the generation and capture of plasticity-related gene products. We will also introduce new findings on PKA-dependent presynaptic mechanisms and in vivo signatures of STC. Having PKA as a key molecule, the goal of this chapter is to provide a unified model of STC that addresses the key questions.