Unified Model of Synaptic Transmission

Abstract

Learning and memory are two of the most fundamental and widely studied processes which underlie neuroscience. The mechanisms facilitating these processes are collectively known as synaptic plasticity. Through the modulation of synapse strength depending on the activity of neurons, synaptic plasticity reshapes the neural network over time. Synaptic plasticity is caused by the release of glutamate from pre-synaptic neurons and the activity of the synapse is mediated by glutamate receptors (AMPA and NMDA), excitatory amino acid transporters (EAAT), Calmodulin (CAM) and related protein kinases (CAMKII) and phosphatases (PP1). The crucial mechanism is that the ion transport into the post-synaptic compartment through ionotropic glutamate receptors (iGluRs) modulates the level of Na+ and Ca++ conductance as well as the number of iGluRs that migrate to the postsynaptic cell membrane. In this study, a unified model incorporating pre-synaptic and post-synaptic transport is developed. The limitations on the simulations due to the complexity and the size of the model are eliminated by coarse-graining in the model and by using hybrid particle/population simulation tools. The effects of different initial concentrations of Na+ and Ca++ and neurotransmitters (glutamate) in different compartments are examined in order to understand how this variables, which may be altered in neurodegenerative diseases such as Alzheimer's and Huntington's, affect synaptic transmission. Overall, the model and simulations are expected to provide insight into new therapeutic strategies.