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<p class=MsoNormal>This archive instantiates the single-cell cortical models
used in (Aberra et al. 2018) and sets up extracellular stimulation with either
a point-current source, to simulate intracortical microstimulation (ICMS), or a
uniform E-field distribution, with a monophasic, rectangular pulse waveform in
both cases. </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Model code used in:</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Aberra AS, Peterchev, AV, Grill WM (2018) Biophysically
Realistic Neuron Models for Simulation of Cortical Stimulation J Neural Eng.
https://doi.org/10.1088/1741-2552/aadbb1
</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>This code was contributed by Aman Aberra (Duke University)</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>ABSTRACT</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Objective. We implemented computational models of human and
rat cortical neurons for simulating the neural response to cortical stimulation
with electromagnetic fields. Approach. We adapted model neurons from the
library of Blue Brain models to reflect biophysical and geometric properties of
both adult rat and human cortical neurons and coupled the model neurons to
exogenous electric fields (E-fields). The models included 3D reconstructed
axonal and dendritic arbors, experimentally-validated electrophysiological
behaviors, and multiple, morphological variants within cell-types. Using these
models, we characterized the single-cell responses to intracortical
microstimulation (ICMS) and uniform E-field with dc as well as pulsed currents.
Main results. The strength–duration and current–distance characteristics of the
model neurons to ICMS agreed with published experimental results, as did the
subthreshold polarization of cell bodies and axon terminals by uniform dc
E-fields. For all forms of stimulation, the lowest threshold elements were
terminals of the axon collaterals, and the dependence of threshold and
polarization on spatial and temporal stimulation parameters was strongly
affected by morphological features of the axonal arbor, including myelination,
diameter, and branching. Significance. These results provide key insights into
the mechanisms of cortical stimulation. The presented models can be used to
study various cortical stimulation modalities while incorporating detailed
spatial and temporal features of the applied E-field. </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Instructions to run the code (assuming NEURON has been
installed): </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>**Linux/macOS (in terminal):</p>
<p class=MsoNormal> unzip the archive</p>
<p class=MsoNormal> cd AberraEtAl2018</p>
<p class=MsoNormal> chmod +x mosinit.command (automatically compiles
mod files in 'mechanisms/' if necessary)</p>
<p class=MsoNormal> Double-click mosinit.command (or launch from
terminal, e.g. ./mosinit.command)</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>**Windows:</p>
<p class=MsoNormal> unzip the archive</p>
<p class=MsoNormal> compile ‘mechanisms/‘ using mknrndll and copy
nrnmech.dll from 'mechanisms/' up one level to 'AberraEtAl2018/' </p>
<p class=MsoNormal> right-click mosinit.ps1 and select “Run with
Powershell”, will probably require giving permission to run</p>
<p class=MsoNormal> **To make short-cut executable with
double-click:</p>
<p class=MsoNormal> right-click mosinit.ps1 and select
“Create shortcut”</p>
<p class=MsoNormal> right-click newly created shortcut
(ends with Shortcut.lnk by default) and select “Properties”</p>
<p class=MsoNormal> in the “Target:” field, add the text
below before the existing text, which should look like this:</p>
<p class=MsoNormal> powershell.exe
-ExececutionPolicy Bypass -File C:\path\to\file…</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>**instructions for creating executable powershell shortcut
can be found here:
https://www.tenforums.com/tutorials/97162-powershell-scripting-run-script-shortcut.html**
</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Additional notes: </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>1) After loading a model neuron, code currently only allows
reloading same model (with same or different parameters), attempting to load a
different model neuron will throw an error</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>2) Stack size must be increased to generate myelinated axons
for most models, so init.hoc should be launched with options included in mosinit.command:</p>
<p class=MsoNormal> </p>
<p class=MsoNormal> nrngui -NSTACK 100000 -NFRAME 20000 init.hoc </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Using either shortcut launches init.hoc with these settings
by default, otherwise the above text should be executed from the terminal/shell</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>3) Loading cell runs color_plotmax() with default settings,
to replot with main axon colored (more well-defined for the pyramidal cells),
type: </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>oc> color_plotmax(2,0)</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Set second argument to 1 to save figure as .eps </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>4) To add new cells from Blue Brain Library:</p>
<p class=MsoNormal> Download cell model folder from: https://bbp.epfl.ch/nmc-portal/downloads</p>
<p class=MsoNormal> Unzip and place directory in
“AberraEtAl2018/cells”</p>
<p class=MsoNormal> comment out “replace_axon()” in template.hoc
within proc biophys() (typically line 117)</p>
<p class=MsoNormal> Add directory name to list of cell names below
last entry in cell_chooser.hoc (currently, L6_TPC_L4_cADpyr231_5)</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>5) After loading, users can apply extracellular stimulation
for a given field using the GUI windows, <b>screenshots with further instructions
(run on macOS) shown below</b></p>
<p class=MsoNormal> </p>
<p class=MsoNormal> </p>
<p class=MsoNormal>References for Blue Brain models:</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>1. Markram H†, Muller E†, Ramaswamy S†, Reimann MW†,
Abdellah M, Sanchez CA, Ailamaki A, Alonso-Nanclares L, Antille N, Arsever S et
al. (2015). Reconstruction and Simulation of Neocortical Microcircuitry. Cell
163:2, 456 - 492. doi: 10.1016/j.cell.2015.09.029</p>
<p class=MsoNormal>† Co-first author</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>2. Ramaswamy S, Courcol J-D, Abdellah M, Adaszewski SR,
Antille N, Arsever S, Atenekeng G, Bilgili A, Brukau Y, Chalimourda A, Chindemi
G, Delalondre F, Dumusc R, Eilemann S, Gevaert ME, Gleeson P, Graham JW,
Hernando JB, Kanari L, Katkov Y, Keller D, King JG, Ranjan R, Reimann MW,
Rössert C, Shi Y, Shillcock JC, Telefont M, Van Geit W, Villafranca Diaz J,
Walker R, Wang Y, Zaninetta SM, DeFelipe J, Hill SL, Muller J, Segev I,
Schürmann F, Muller EB and Markram H (2015). The neocortical microcircuit
collaboration portal: a resource for rat somatosensory cortex. Front. Neural
Circuits 9:44. doi: 10.3389/fncir.2015.00044</p>
<p class=MsoNormal> </p>
<p class=MsoNormal>If mod files are successfully compiled and loaded, launching
mosinit.command should produce the following output:</p>
<p class=MsoNormal> </p>
<p class=MsoNormal align=center style='text-align:center'><img width=450
height=253 id="Picture 1" src="README.fld/image001.png"></p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Selecting, for example, <i>cell 20: L5_TTPC2_cADpyr232_5</i>
in the “Choose Cell” window loads the cell and generates a Shape plot with the
Myelin, Node, and Unmyelinated axonal sections as well as the apical and basal
dendrites all colored differently. Color legend can be found in Fig. 1 or Fig.
7a of (Aberra et al. 2018). </p>
<p class=MsoNormal> </p>
<p class=MsoNormal align=center style='text-align:center'><img width=450
height=253 id="Picture 2" src="README.fld/image002.png"></p>
<p class=MsoNormal> </p>
<p class=MsoNormal>Next, to simulate ICMS or uniform E-field stimulation, click
on any of the parameter buttons, or enter a value in a parameter text box, and hit
“Enter” on the keyboard in both the “Spatial parameters” and “Temporal
parameters” windows. Once both sets of parameters are initialized, indicated by
messages confirming the potentials and waveform have been set in the terminal,
the simulation can be run using the “RunControl” window. Note the red marker
indicating the location of the electrode tip, i.e. the point-source, used for
calculating potentials. </p>
<p class=MsoNormal align=center style='text-align:center'><img width=450
height=253 id="Picture 3" src="README.fld/image003.png"></p>
<p class=MsoNormal> </p>
<p class=MsoNormal>For uniform E-field stimulation, a violet “dummy section”
indicates the E-field direction defined by the polar and azimuthal angles,
theta and phi, respectively, with the E-field pointing away from the cell body.
<b>Note: when using uniform E-field stimulation theta and phi are calculated by
treating the y-axis (upwards, in the page) in the NEURON coordinate system as
the z-axis, and by treating the NEURON z-axis (positive, out of the page) as
the negative y-axis (positive, into the page). This is in contrast to the
coordinates used for the ICMS electrode position, which use the NEURON
coordinate system, i.e. z-axis is positive pointing out of the page. </b></p>
<p class=MsoNormal> </p>
<p class=MsoNormal>To visualize the membrane potential response, a “Voltage
axis” or “Shape plot” can be generated from the “Graph” menu In the “NEURON
Main Menu” window (top left). Examples: </p>
<p class=MsoNormal> </p>
<p class=MsoNormal><b>ICMS</b></p>
<p class=MsoNormal><b> </b></p>
<p class=MsoNormal align=center style='text-align:center'><img width=450
height=253 id="Picture 5" src="README.fld/image004.png"></p>
<p class=MsoNormal align=center style='text-align:center'> </p>
<p class=MsoNormal align=center style='text-align:center'> </p>
<p class=MsoNormal><b> </b></p>
<p class=MsoNormal><b>Uniform E-field stimulation</b></p>
<p class=MsoNormal align=center style='text-align:center'> </p>
<p class=MsoNormal align=center style='text-align:center'><img width=450
height=253 id="Picture 6" src="README.fld/image005.png"></p>
<p class=MsoNormal align=center style='text-align:center'> </p>
</div>
<p>
<b>Changelog:</b><br>
2022-05: Updated MOD files to contain valid C++ and be compatible with the upcoming versions 8.2 and 9.0 of NEURON.
</p>
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