Temporal sensitivity of protein kinase A activation in a stochastic reaction-diffusion model of late phase long term potentiation

Abstract

Introduction The ability of neurons within the hippocampus to differentially respond to specific temporal and spatial patterns of stimulation underlies the storage of memory and information in neural circuits. Signal transduction pathways are critical for information storage and alterations in key signaling molecules, such as the cAMP-dependent protein kinase (PKA) signaling pathway, modify both hippocampus-dependent learning and a form of synaptic plasticity known as late-phase long-term potentiation (L-LTP). The induction of late phase LTP (L-LTP) in the CA1 region of the hippocampus requires several kinases, including CaMKII and PKA, which are activated by calcium-dependent signaling processes and other intracellular signaling pathways. Many of the biochemical reactions leading to activation of these critical kinases are localized to dendritic spines. The small size of theses spines implies that small numbers of molecules are involved; the presence of anchoring proteins and the morphology of neurons implies that molecules are inhomogeneously distributed. Therefore, to accurately model these cellular signaling events requires software for stochastic reaction-diffusion systems.