Modeling Signal Transduction Leading to Synaptic Plasticity: Evaluation and Comparison of Five Models

Neurons respond to variations in extracellular and intracellular environment by modifying their synaptic and intrinsic membrane properties. When a presynaptic neuron passes an electrical or chemical signal to a postsynaptic neuron, changes in the synapse occur. Long-term potentiation (LTP), also known as strengthening, and long-term depression (LTD), also known as weakening, of synapses are two forms of synaptic plasticity. Both LTP and LTD participate in storing information and inducing processes that are thought to ultimately lead to learning (see, e.g., [1]). The main focus in the research on synaptic plasticity in vertebrates has been on LTP and LTD in cornu ammonis 1 (CA1) region of the hippocampus [1] because hippocampus is especially important in the formation and retrieval of declarative memories. Several mechanisms have been shown to be the reason for changes in synaptic strength; for example, changes in neurotransmitter release, conductivity of receptors, numbers of receptors, numbers of active synapses, and structure of synapses [2].At present, there are more than a hundred molecules found important in LTP/LTD, some of which are key components for LTP/LTD formation and others being able to modulate the ability to generate LTP/LTD [1]. Strong evidence supports the finding that calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) meets the criteria for being the essential molecule to LTP [3]. Protein kinases add phosphates to proteins, and, on the other hand, protein phosphatases remove phosphates from proteins to activate or deactivate them. It is hence straightforward to consider that also the protein phosphatases, such as protein phosphatases 1, 2A, and 2B (PP1, PP2A, and PP2B, a.k.a. calcineurin (CaN)), have important roles in synaptic plasticity [4].More than a hundred computational models, simple and more complex ones, have been developed to describe the mechanisms behind synaptic plasticity at the biochemical level (see, e.g., [5, 6])