Distal spike initiation zone location estimation by morphological simulation of ionic current filtering demonstrated in a novel model of an identified Drosophila motoneuron

Studying ion channel currents generated distally from the recording site is difficult because of artifacts caused by poor space clamp and membrane filtering. A computational model can quantify artifact parameters for correction by simulating the currents only if their exact anatomical location is kn...

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Veröffentlicht in:PLoS computational biology 2015-05, Vol.11 (5), p.e1004189-e1004189
Hauptverfasser: Günay, Cengiz, Sieling, Fred H, Dharmar, Logesh, Lin, Wei-Hsiang, Wolfram, Verena, Marley, Richard, Baines, Richard A, Prinz, Astrid A
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container_issue 5
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container_title PLoS computational biology
container_volume 11
creator Günay, Cengiz
Sieling, Fred H
Dharmar, Logesh
Lin, Wei-Hsiang
Wolfram, Verena
Marley, Richard
Baines, Richard A
Prinz, Astrid A
description Studying ion channel currents generated distally from the recording site is difficult because of artifacts caused by poor space clamp and membrane filtering. A computational model can quantify artifact parameters for correction by simulating the currents only if their exact anatomical location is known. We propose that the same artifacts that confound current recordings can help pinpoint the source of those currents by providing a signature of the neuron's morphology. This method can improve the recording quality of currents initiated at the spike initiation zone (SIZ) that are often distal to the soma in invertebrate neurons. Drosophila being a valuable tool for characterizing ion currents, we estimated the SIZ location and quantified artifacts in an identified motoneuron, aCC/MN1-Ib, by constructing a novel multicompartmental model. Initial simulation of the measured biophysical channel properties in an isopotential Hodgkin-Huxley type neuron model partially replicated firing characteristics. Adding a second distal compartment, which contained spike-generating Na+ and K+ currents, was sufficient to simulate aCC's in vivo activity signature. Matching this signature using a reconstructed morphology predicted that the SIZ is on aCC's primary axon, 70 μm after the most distal dendritic branching point. From SIZ to soma, we observed and quantified selective morphological filtering of fast activating currents. Non-inactivating K+ currents are filtered ∼3 times less and despite their large magnitude at the soma they could be as distal as Na+ currents. The peak of transient component (NaT) of the voltage-activated Na+ current is also filtered more than the magnitude of slower persistent component (NaP), which can contribute to seizures. The corrected NaP/NaT ratio explains the previously observed discrepancy when the same channel is expressed in different cells. In summary, we used an in vivo signature to estimate ion channel location and recording artifacts, which can be applied to other neurons.
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Adding a second distal compartment, which contained spike-generating Na+ and K+ currents, was sufficient to simulate aCC's in vivo activity signature. Matching this signature using a reconstructed morphology predicted that the SIZ is on aCC's primary axon, 70 μm after the most distal dendritic branching point. From SIZ to soma, we observed and quantified selective morphological filtering of fast activating currents. Non-inactivating K+ currents are filtered ∼3 times less and despite their large magnitude at the soma they could be as distal as Na+ currents. The peak of transient component (NaT) of the voltage-activated Na+ current is also filtered more than the magnitude of slower persistent component (NaP), which can contribute to seizures. The corrected NaP/NaT ratio explains the previously observed discrepancy when the same channel is expressed in different cells. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Motoneuron. 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A computational model can quantify artifact parameters for correction by simulating the currents only if their exact anatomical location is known. We propose that the same artifacts that confound current recordings can help pinpoint the source of those currents by providing a signature of the neuron's morphology. This method can improve the recording quality of currents initiated at the spike initiation zone (SIZ) that are often distal to the soma in invertebrate neurons. Drosophila being a valuable tool for characterizing ion currents, we estimated the SIZ location and quantified artifacts in an identified motoneuron, aCC/MN1-Ib, by constructing a novel multicompartmental model. Initial simulation of the measured biophysical channel properties in an isopotential Hodgkin-Huxley type neuron model partially replicated firing characteristics. Adding a second distal compartment, which contained spike-generating Na+ and K+ currents, was sufficient to simulate aCC's in vivo activity signature. Matching this signature using a reconstructed morphology predicted that the SIZ is on aCC's primary axon, 70 μm after the most distal dendritic branching point. From SIZ to soma, we observed and quantified selective morphological filtering of fast activating currents. Non-inactivating K+ currents are filtered ∼3 times less and despite their large magnitude at the soma they could be as distal as Na+ currents. The peak of transient component (NaT) of the voltage-activated Na+ current is also filtered more than the magnitude of slower persistent component (NaP), which can contribute to seizures. The corrected NaP/NaT ratio explains the previously observed discrepancy when the same channel is expressed in different cells. In summary, we used an in vivo signature to estimate ion channel location and recording artifacts, which can be applied to other neurons.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25978332</pmid><doi>10.1371/journal.pcbi.1004189</doi><oa>free_for_read</oa></addata></record>
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subjects Action Potentials
Animals
Biophysical Phenomena
Biophysics
Computational Biology
Computer Simulation
Drosophila
Drosophila melanogaster - cytology
Drosophila melanogaster - physiology
Electrophysiological Phenomena
Experiments
Insects
Ion Channels - metabolism
Models, Neurological
Morphology
Motor neurons
Motor Neurons - physiology
Motor Neurons - ultrastructure
Neural circuitry
Neurons
Patch-Clamp Techniques
Physiological aspects
Physiology
Simulation
title Distal spike initiation zone location estimation by morphological simulation of ionic current filtering demonstrated in a novel model of an identified Drosophila motoneuron
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