A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling
The neurovascular coupling (NVC) connects neuronal activity to hemodynamic responses in the brain. This connection is the basis for the interpretation of functional magnetic resonance imaging data. Despite the central role of this coupling, we lack detailed knowledge about cell-specific contribution...
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doaj-b8fc19c20fb949febd8c631713bd33922020-11-25T02:58:37ZengElsevierNeuroImage1095-95722020-07-01215116827A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular couplingSebastian Sten0Fredrik Elinder1Gunnar Cedersund2Maria Engström3Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Biomedical Engineering, Linköping University, Linköping, SwedenDepartment of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Corresponding author. CMIV, Linköping University/US, 581 83, Linköping, Sweden.The neurovascular coupling (NVC) connects neuronal activity to hemodynamic responses in the brain. This connection is the basis for the interpretation of functional magnetic resonance imaging data. Despite the central role of this coupling, we lack detailed knowledge about cell-specific contributions and our knowledge about NVC is mainly based on animal experiments performed during anesthesia. Anesthetics are known to affect neuronal excitability, but how this affects the vessel diameters is not known. Due to the high complexity of NVC data, mathematical modeling is needed for a meaningful analysis. However, neither the relevant neuronal subtypes nor the effects of anesthetics are covered by current models. Here, we present a mathematical model including GABAergic interneurons and pyramidal neurons, as well as the effect of an anesthetic agent. The model is consistent with data from optogenetic experiments from both awake and anesthetized animals, and it correctly predicts data from experiments with different pharmacological modulators. The analysis suggests that no downstream anesthetic effects are necessary if one of the GABAergic interneuron signaling pathways include a Michaelis-Menten expression. This is the first example of a quantitative model that includes both the cell-specific contributions and the effect of an anesthetic agent on the NVC.http://www.sciencedirect.com/science/article/pii/S1053811920303141Functional hyperemiaMathematical modelingCerebral hemodynamicsSystems biologyFunctional magnetic resonance imaging (fMRI)Blood oxygen level dependent (BOLD) response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sebastian Sten Fredrik Elinder Gunnar Cedersund Maria Engström |
spellingShingle |
Sebastian Sten Fredrik Elinder Gunnar Cedersund Maria Engström A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling NeuroImage Functional hyperemia Mathematical modeling Cerebral hemodynamics Systems biology Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) response |
author_facet |
Sebastian Sten Fredrik Elinder Gunnar Cedersund Maria Engström |
author_sort |
Sebastian Sten |
title |
A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
title_short |
A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
title_full |
A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
title_fullStr |
A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
title_full_unstemmed |
A quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
title_sort |
quantitative analysis of cell-specific contributions and the role of anesthetics to the neurovascular coupling |
publisher |
Elsevier |
series |
NeuroImage |
issn |
1095-9572 |
publishDate |
2020-07-01 |
description |
The neurovascular coupling (NVC) connects neuronal activity to hemodynamic responses in the brain. This connection is the basis for the interpretation of functional magnetic resonance imaging data. Despite the central role of this coupling, we lack detailed knowledge about cell-specific contributions and our knowledge about NVC is mainly based on animal experiments performed during anesthesia. Anesthetics are known to affect neuronal excitability, but how this affects the vessel diameters is not known. Due to the high complexity of NVC data, mathematical modeling is needed for a meaningful analysis. However, neither the relevant neuronal subtypes nor the effects of anesthetics are covered by current models. Here, we present a mathematical model including GABAergic interneurons and pyramidal neurons, as well as the effect of an anesthetic agent. The model is consistent with data from optogenetic experiments from both awake and anesthetized animals, and it correctly predicts data from experiments with different pharmacological modulators. The analysis suggests that no downstream anesthetic effects are necessary if one of the GABAergic interneuron signaling pathways include a Michaelis-Menten expression. This is the first example of a quantitative model that includes both the cell-specific contributions and the effect of an anesthetic agent on the NVC. |
topic |
Functional hyperemia Mathematical modeling Cerebral hemodynamics Systems biology Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) response |
url |
http://www.sciencedirect.com/science/article/pii/S1053811920303141 |
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