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Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells

The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer’s disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhi...

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Autores principales: Tait, Luke, Wedgwood, Kyle, Tsaneva-Atanasova, Krasimira, Brown, Jon T., Goodfellow, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947116/
https://www.ncbi.nlm.nih.gov/pubmed/29654854
http://dx.doi.org/10.1016/j.jtbi.2018.04.013
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author Tait, Luke
Wedgwood, Kyle
Tsaneva-Atanasova, Krasimira
Brown, Jon T.
Goodfellow, Marc
author_facet Tait, Luke
Wedgwood, Kyle
Tsaneva-Atanasova, Krasimira
Brown, Jon T.
Goodfellow, Marc
author_sort Tait, Luke
collection PubMed
description The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer’s disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4–12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance.
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spelling pubmed-59471162018-07-14 Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells Tait, Luke Wedgwood, Kyle Tsaneva-Atanasova, Krasimira Brown, Jon T. Goodfellow, Marc J Theor Biol Article The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer’s disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4–12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Elsevier 2018-07-14 /pmc/articles/PMC5947116/ /pubmed/29654854 http://dx.doi.org/10.1016/j.jtbi.2018.04.013 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tait, Luke
Wedgwood, Kyle
Tsaneva-Atanasova, Krasimira
Brown, Jon T.
Goodfellow, Marc
Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title_full Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title_fullStr Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title_full_unstemmed Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title_short Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
title_sort control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947116/
https://www.ncbi.nlm.nih.gov/pubmed/29654854
http://dx.doi.org/10.1016/j.jtbi.2018.04.013
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