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Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance

Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful “tools” that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With adva...

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Autores principales: Sun, Zhenyang, Crompton, David, Lankarany, Milad, Skinner, Frances K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936813/
https://www.ncbi.nlm.nih.gov/pubmed/36817648
http://dx.doi.org/10.3389/fncir.2023.1076761
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author Sun, Zhenyang
Crompton, David
Lankarany, Milad
Skinner, Frances K.
author_facet Sun, Zhenyang
Crompton, David
Lankarany, Milad
Skinner, Frances K.
author_sort Sun, Zhenyang
collection PubMed
description Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful “tools” that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With advances in cell imaging and computational power, multi-compartment models with morphological accuracy are becoming common practice. However, as more biological details are added, they make extensive explorations and analyses more challenging largely due to their huge computational expense. Here, we focus on oriens-lacunosum/moleculare (OLM) cell models. OLM cells can contribute to functionally relevant theta rhythms in the hippocampus by virtue of their ability to express spiking resonance at theta frequencies, but what characteristics underlie this is far from clear. We converted a previously developed detailed multi-compartment OLM cell model into a reduced single compartment model that retained biophysical fidelity with its underlying ion currents. We showed that the reduced OLM cell model can capture complex output that includes spiking resonance in in vivo-like scenarios as previously obtained with the multi-compartment model. Using the reduced model, we were able to greatly expand our in vivo-like scenarios. Applying spike-triggered average analyses, we were able to to determine that it is a combination of hyperpolarization-activated cation and muscarinic type potassium currents that specifically allow OLM cells to exhibit spiking resonance at theta frequencies. Further, we developed a robust Kalman Filtering (KF) method to estimate parameters of the reduced model in real-time. We showed that it may be possible to directly estimate conductance parameters from experiments since this KF method can reliably extract parameter values from model voltage recordings. Overall, our work showcases how the contribution of cellular biophysical current details could be determined and assessed for spiking resonance. As well, our work shows that it may be possible to directly extract these parameters from current clamp voltage recordings.
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spelling pubmed-99368132023-02-18 Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance Sun, Zhenyang Crompton, David Lankarany, Milad Skinner, Frances K. Front Neural Circuits Neuroscience Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful “tools” that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With advances in cell imaging and computational power, multi-compartment models with morphological accuracy are becoming common practice. However, as more biological details are added, they make extensive explorations and analyses more challenging largely due to their huge computational expense. Here, we focus on oriens-lacunosum/moleculare (OLM) cell models. OLM cells can contribute to functionally relevant theta rhythms in the hippocampus by virtue of their ability to express spiking resonance at theta frequencies, but what characteristics underlie this is far from clear. We converted a previously developed detailed multi-compartment OLM cell model into a reduced single compartment model that retained biophysical fidelity with its underlying ion currents. We showed that the reduced OLM cell model can capture complex output that includes spiking resonance in in vivo-like scenarios as previously obtained with the multi-compartment model. Using the reduced model, we were able to greatly expand our in vivo-like scenarios. Applying spike-triggered average analyses, we were able to to determine that it is a combination of hyperpolarization-activated cation and muscarinic type potassium currents that specifically allow OLM cells to exhibit spiking resonance at theta frequencies. Further, we developed a robust Kalman Filtering (KF) method to estimate parameters of the reduced model in real-time. We showed that it may be possible to directly estimate conductance parameters from experiments since this KF method can reliably extract parameter values from model voltage recordings. Overall, our work showcases how the contribution of cellular biophysical current details could be determined and assessed for spiking resonance. As well, our work shows that it may be possible to directly extract these parameters from current clamp voltage recordings. Frontiers Media S.A. 2023-02-03 /pmc/articles/PMC9936813/ /pubmed/36817648 http://dx.doi.org/10.3389/fncir.2023.1076761 Text en Copyright © 2023 Sun, Crompton, Lankarany and Skinner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Sun, Zhenyang
Crompton, David
Lankarany, Milad
Skinner, Frances K.
Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title_full Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title_fullStr Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title_full_unstemmed Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title_short Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
title_sort reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936813/
https://www.ncbi.nlm.nih.gov/pubmed/36817648
http://dx.doi.org/10.3389/fncir.2023.1076761
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