MODELING GLUTAMATERGIC SYNAPSES: INSIGHTS INTO MECHANISMS REGULATING SYNAPTIC EFFICACY
Author(s):
JEAN-MARIE C. BOUTEILLER BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France MICHEL BAUDRY BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France SUSHMITA L. ALLAM BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France RENAUD J. GREGET BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France SERGE BISCHOFF BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France THEODORE W. BERGER BME Department, University of Southern California, Los Angeles, CA 90089, USA Rhenovia Pharma, Mulhouse, France
Dedication:
This paper is dedicated to Gilbert
Chauvet. Gilbert was a friend, a collaborator, and an inspiration for
much of this effort. He is being dearly missed and we hope that this
article will contribute to maintain the fire that he ignited.
History:
Received 15 April 2008 Accepted 25 April 2008
Abstract:
The hippocampal formation is
critically involved for the long-term storage of various forms of
information, and it is widely believed that the phenomenon of long-term
potentiation (LTP) of synaptic transmission is a molecular/cellular
mechanism participating in memory formation. Although several high
level models of hippocampal function have been developed, they do not
incorporate detailed molecular information of the type necessary to
understand the contribution of individual molecular events to the
mechanisms underlying LTP and learning and memory. We are therefore
developing new technological tools based on mathematical modeling and
computer simulation of the molecular processes taking place in
realistic biological networks to reach such an understanding. This
article briefly summarizes the approach we are using and illustrates it
by presenting data regarding the effects of changing the number of AMPA
receptors on various features of glutamatergic transmission, including
NMDA receptor-mediated responses and paired-pulse facilitation. We
conclude by discussing the significance of these results and providing
some ideas for future directions with this approach.