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  5. Stochastic hybrid model of spontaneous dendritic NMDA spikes
 
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Stochastic hybrid model of spontaneous dendritic NMDA spikes
File(s)
NMDA.pdf (661.47 KB)
Accepted version
Author(s)
Bressloff, Paul C
Newby, Jay M
Type
Journal Article
Abstract
Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na+ ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I–V) characteristics of an NMDAR so that it behaves like a voltage-gated Na+ channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na+ channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K+ channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na+ and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the combined effects of glutamate unbinding and noise on the termination of a spike.
Date Issued
2014-02
Date Acceptance
2013-12-20
Citation
Physical Biology, 2014, 11 (1)
URI
http://hdl.handle.net/10044/1/107519
URL
http://dx.doi.org/10.1088/1478-3975/11/1/016006
DOI
https://www.dx.doi.org/10.1088/1478-3975/11/1/016006
ISSN
1478-3967
Publisher
IOP Publishing
Journal / Book Title
Physical Biology
Volume
11
Issue
1
Copyright Statement
Copyright © 2014 IOP Publishing Ltd. This is an author-created, un-copyedited version of an article published in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at 10.1088/1478-3975/11/1/016006
Identifier
http://dx.doi.org/10.1088/1478-3975/11/1/016006
Publication Status
Published
Article Number
016006
Date Publish Online
2014-01-29
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