Document Type

Article

Publication Title

Mathematical Biosciences

Publisher

Elsevier

Publication Date

8-2012

Volume

240

Issue

2

Disciplines

Medical Sciences | Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

Abstract

A model of synaptic and extra-synaptic excitatory signaling in the hippocampus is presented. The model is used to analytically evaluate the potential contributions of homosynaptic and heterosynaptic glutamate spill-over to receptor signaling during an electrophysiological experiment in which glutamate transporters are pharmacologically blocked. Inhibition of glutamate uptake selectively prolongs the decay kinetics of the second field excitatory postsynaptic potential evoked by paired pulse stimulation of Schaffer collateral axons in area CA1. The model includes AMPA and NMDA glutamate receptors, and the removal of glutamate by transporters and diffusion. We establish analytically that the prolongation cannot be caused by local effects, i.e., the transporters acting within or near the synapse. In contrast, a time profile of glutamate consistent with spill-over from adjacent synapses can explain the effect. The different reaction kinetics of AMPA and NMDA receptors have a significant role in reproducing the experimental results, as explained by analysis of the ODEs governing the reactions.

Keywords

neurotransmitter spill-over; hippocampus; NMDA receptors; AMPA receptors; glutamate transporters

DOI

https://doi.org/10.1016/j.mbs.2012.07.004

Comments

This version is the author accepted manuscript.

Rights

Copyright © 2012 Elsevier Inc. All rights reserved.

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