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 co...

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Bibliographic Details
Published inMethods in molecular biology (Clifton, N.J.) Vol. 1677; p. 291
Main Authors Keller, A Florence, Bouteiller, Jean-Marie C, Berger, Theodore W
Format Journal Article
LanguageEnglish
Published United States 2017
Subjects
Algorithms
Animals
Computer Simulation
Humans
Kinetics
Patch-Clamp Techniques
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses - metabolism
Synaptic Transmission - physiology
Synaptic function
Optimization algorithm
NMDA receptors model
Pharmacology
Computational model; kinetic models
Ordinary differential equation
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Summary: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.
ISSN:1940-6029
DOI:10.1007/978-1-4939-7321-7_17