Development of a Computational Approach/Model to Explore NMDA Receptors Functions.

Modern laboratory techniques allow studying NMDA receptors (NMDAR) either anatomically with specific antibodies coupled to sophisticated confocal microscopy, or physiologically by live imaging or electrophysiological techniques. However, NMDARs are not fixed in time and space and changes in their composition and/or distribution on the post-synaptic membrane may significantly impact the synaptic strength and overall function. The computational modeling approach therefore constitutes a complementary tool for investigating the properties of biological systems based on the knowledge provided by the lab experiments.Here, we describe a general computational method aiming at developing kinetic Markov-chain based models of NMDARs subtypes capable of reproducing various experimental results. These models are then used to make predictions on additional (non-obvious) properties and on their role in synaptic function under various physiological and pharmacological conditions. For the purpose of this book chapter, we will focus on the method used to develop a NMDAR model that includes pharmacological site of action of different compounds. Notably, this elementary model can subsequently be included in a neuron model (not described in detail here) to explore the impact of their differential distribution on synaptic functions.