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Initial updated figures with emacs .org files in ./Figure_org/

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#+TITLE: Figure update
#+AUTHOR: Nils Koch
#+DATE:
#+startup: beamer
#+BEAMER_THEME: Boadilla
#+COLUMNS: %45ITEM %10BEAMER_env(Env) %10BEAMER_act(Act) %4BEAMER_col(Col) %8BEAMER_opt(Opt)
#+PROPERTY: BEAMER_col_ALL 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0.0 :ETC
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#+COLUMNS: %40ITEM %10BEAMER_env(Env) %9BEAMER_envargs(Env Args) %4BEAMER_col(Col) %10BEAMER_extra(Extra)
#+BEAMER_HEADER: \subtitle{}
# '+BEAMER_HEADER: \AtBeginSection[]{\begin{frame}<beamer>\frametitle{\secname}\end{frame}}
#+TAGS: noexport(n)
# 'Use Next line for 16:9
# '+LATEX_HEADER: \usepackage[orientation=landscape,size=custom,width=16,height=9.75,scale=0.5,debug]{beamerposter}
#+LaTeX_HEADER:\usepackage[backend=bibtex,sorting=none, style=numeric-comp, citestyle=numeric-comp]{biblatex}
#+LATEX_HEADER: \usepackage{endnotes}
#+LaTeX_HEADER:\bibliography{H2v01.bib} %% point at your bib file
#+LaTeX_CLASS: beamer
#+LaTeX_CLASS_OPTIONS: [presentation]
#+LATEX_HEADER: \usepackage{tikz,bm}
#+LATEX_HEADER: \usepackage{epstopdf}
#+LATEX_HEADER: \graphicspath{{./Figures/}}
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#+LATEX_HEADER: \setbeamercolor{title}{fg=mcgillred}
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#+LATEX_HEADER: \newcommand{\nox}{\(\mathrm{NO_{x}}\)}
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#+LATEX_HEADER: \setlength\abovecaptionskip{-5pt}
#+LATEX_HEADER: \renewcommand{\footnote}{\endnote}
#+LATEX_HEADER: \usepackage{animate}
# +END_EXPORT
* Introduction
*** Intro to org to Beamer
- This is not that visually appealling, but I haven't taken the time to set the colors and style to my liking in the Latex header
- I have tried to include as many examples of things I find useful as possible
- sometimes this makes the slide not make much sense, but the example of how to do things is hopefully useful
- The only slight pain with using org for both Beamer and normal Latex pdf is:
- you cannot have the pdf open in some pdf viewers and export to it (eg adobe)
- I use Sumatra (https://www.sumatrapdfreader.org/free-pdf-reader)
- can have your pdf open in sumatra, export to it and it will update the pdf to the new exported file while open
*** Slide not exported :noexport:
- This slide is not exported when the noexport tag is present
- to remove the tag: ctrl-c crtl-q space enter
- to add a noexport tag: ctrl-x ctrl-q n enter
- this can be very useful if you have a comprehensive slide set and you only want to present some slides or sections
- this can also be done on sections (e.g. * Introduction)
* Figure update
*** Firing Characterization
\vspace{-0.5cm}
**** Col left :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.65
:BEAMER_opt: [t]
:END:
- Firing is a complicated phenomenon
- How to best characterize it?
- rheobase
- AUC
**** Col right :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.35
:BEAMER_opt: [t]
:END:
#+ATTR_LATEX: :width 0.95\textwidth
[[file:firing_characterization.pdf]]
*** Diversity in Firing Properties of the Models
#+ATTR_LATEX: :width 0.55\textwidth
[[file:diversity_in_firing.pdf]]
*** Sensitivy analysis: OFAT
\vspace{-2cm}
- [ ] one factor at a time sensitivity analysis
- simulate firing responses
- compute fI curves
- get rheobase
- compute AUC
*** Rheobase sensitivity Analysis
#+ATTR_LATEX: :width 0.85\textwidth
[[file:rheobase_correlation.pdf]]
\tiny Koch et al. 2022
*** AUC Sensitivity Analysis
- AUC = area under the curve
#+ATTR_LATEX: :width 0.75\textwidth
[[file:AUC_correlation.pdf]]
- AUC over the initial non-zero fI curve is a proxy for slope
*** \(K_V1.1\) Mutations
#+ATTR_LATEX: :width 0.95\textwidth
[[file:simulation_model_comparison.pdf]]
*** Ramp Firing
#+ATTR_LATEX: :width 0.95\textwidth
[[file:ramp_firing.pdf]]

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# Instructions for org mode export
# - to get export options: ctrl-c ctrl-e
# - to export as latex pdf: ctrl-c ctrl-e l p
#+OPTIONS: ':nil *:nil -:t ::t <:t H:3 \n:nil ^:t arch:headline
#+OPTIONS: author:nil broken-links:nil c:nil creator:nil
#+OPTIONS: d:(not "LOGBOOK") date:nil e:t email:nil f:t inline:t num:nil
#+OPTIONS: p:nil pri:nil prop:nil stat:t tags:t tasks:t tex:t
#+OPTIONS: timestamp:t title:nil toc:nil todo:nil |:t
#+TITLE: Nils Koch
#+DATE: <2021-08-16 Mon>
#+EMAIL: nils.koch@mail.mcgill.ca
#+TAGS: noexport(n)
#+LATEX_CLASS: article
#+LATEX_CLASS_OPTIONS: [letterpaper,10pt]
#+LATEX_HEADER: \usepackage[margin=0.6in]{geometry}
#+LATEX_HEADER: \usepackage{fontawesome}
#+LATEX_HEADER: \usepackage{titling}
#+LATEX_HEADER: \usepackage{titlesec}
#+LATEX_HEADER: \usepackage{fancyhdr}
#+LATEX_HEADER: \usepackage{setspace}
#+LATEX_HEADER: \usepackage{xcolor}
#+LATEX_HEADER: \usepackage{tabularx,xspace}
#+LATEX_HEADER: \usepackage{url}
#+LATEX_HEADER: \usepackage{academicons}
#+LATEX_HEADER: \usepackage{float}
#+LATEX_HEADER: \usepackage{hyperref}
#+LATEX_HEADER: \parindent=0in
#+LATEX_HEADER: \def\refname{\large References}
#+LATEX_HEADER: \newcommand{\eg}{e.g.\ }
#+LATEX_HEADER: \newcommand{\ie}{i.e.,\xspace }
#+LATEX_HEADER: \newcommand{\Aref}[1]{[A\ref{it:#1}]}
#+LATEX_HEADER: \newcommand{\Cref}[1]{[C\ref{it:#1}]}
#+LATEX_HEADER: \newcommand{\Pref}[1]{[P\ref{it:#1}]}
#+LATEX_HEADER: \usepackage{academicons}
#+LATEX_HEADER: \usepackage[breaklinks=true]{hyperref}
#+LATEX_HEADER: \usepackage{graphicx}
#+LATEX_HEADER: \usepackage{graphbox}
#+LATEX_HEADER: \usepackage{matlab-prettifier}
#+LATEX_HEADER: \usepackage[scaled]{helvet} \renewcommand\familydefault{\sfdefault}
#+LATEX_HEADER: \graphicspath{{../Figures/}}
#+LATEX_HEADER_EXTRA:
# For citation colors
#+LATEX_HEADER_EXTRA: \hypersetup{
#+LATEX_HEADER_EXTRA: colorlinks,
#+LATEX_HEADER_EXTRA: linkcolor={red!50!black},
#+LATEX_HEADER_EXTRA: citecolor={blue!50!black},
#+LATEX_HEADER_EXTRA: urlcolor={black!70}
#+LATEX_HEADER_EXTRA: }
#+DESCRIPTION:
#+KEYWORDS:
#+subtitle:
#+LATEX_COMPILER: pdflatex
#+BEGIN_EXPORT latex
\renewcommand{\maketitle}
\maketitle{
\begin{center}
\Huge \textbf{Update on Figures}}}\\
\end{center}
}
%\thispagestyle{empty} %remove header on first page
\titleformat{\section}{\Large\bfseries}{\thesection}{0pt}{}
\titleformat{\subsection}{\large\bfseries}{\thesection}{0pt}{}
\titlespacing*{\section}{0pt}{0ex}{0ex}
\titlespacing*{\subsection}{0pt}{0ex}{0ex}
\titlespacing*{\itemsep}{0pt}{0ex}{0ex}
\pagestyle{fancy}
\fancyhf{}
\renewcommand{\headrulewidth}{0pt} % remove lines as well
\renewcommand{\footrulewidth}{0pt} % remove lines as well
%\lfoot{\textcolor{black!50}{\footnotesize \today}}
%\cfoot{\textcolor{black!50}{\footnotesize Nils Koch }}
\rfoot{\textcolor{black!50}{\thepage}}
%\lhead{}
\chead{\today}
%\rhead{}
\newcommand{\squishlist}{
\begin{list}{$\bullet$}
{ \setlength{\itemsep}{0pt} \setlength{\parsep}{3pt} \setlength{\topsep}{3pt} \setlength{\partopsep}{0pt}
\setlength{\leftmargin}{1.5em} \setlength{\labelwidth}{1em} \setlength{\labelsep}{0.5em} } }
\newcommand{\squishend}{\end{list} }
#+END_EXPORT
* Firing Characterization:
** Question figure addresses:
Firing is a complicated phenomenon. How can it be simply characterized to compare the
effects of changes in current properties?
** Method by which data is generated:
Schematic diagram that does not contain underlying data - contains different square
root functions.
** Conclusion from Figure:
Firing can be characterized by the rheobase and the AUC (proprotional to the increase in
firing after the rheobase). The rheobase and firing in a small range above it (AUC) are
likely important for determining network excitability (I think this makes sense,
would need references to support this).
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=10cm]{firing_characterization.pdf}
\caption{A. Demonstrates AUC in cyan. B. Demonstrates what combinations of increased and
decreased rheobase and AUC look like in terms of fI curves.}
\label{fig:firing_charact}
\end{figure}
#+END_EXPORT
* Diversity in Model Firing:
We have used a number of neuronal models that do not burst to look at the effects
of changes in current properties in firing given different cell types/current
environments
** Question figure addresses:
Which model is used?
** Rationale:
The effect of a change in a current property cannot be assessed in only one cell
type to understand the general effects of this change and to assess whether differences
occur across cell types.
** Method by which data is generated:
Models from different sources are used and an example spike train is shown for each model
along with a fI curve. The black dot on the fI curve indicates where the spike train is
taken from and the green and red dots indicate the current at which the first and last
spike occurs from an increasing and decreasing current ramp respectively. (These ramps
can be seen in the ramp figure at the end).
** Conclusion from Figure:
The models use are diverse and display a variety of spike shapes, firing behaviours, and
fI curve shapes.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{diversity_in_firing.pdf}
\caption{Spike trains and corresponding fI curves from: A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+ current for Kv1.1. The black
dot on the fI curve indicates where the spike train is taken from and the green and red
dots indicate the current at which the first and last spike occurs from an increasing and
decreasing current ramp respectively.}
\label{fig:div_firing}
\end{figure}
#+END_EXPORT
* IB model issue: :noexport:
** Issue Background:
IB (intrinsicially bursting) model from Pospischil et al. 2008 uses a leak conductance
of 0.1. This results in bursting like firing initially (see bottom right of Figure
\ref{fig:IB}) and requires large currents to be injected (> 0.75 nA). When the Kv1.1
current is added to this model (bottom right Figure \ref{fig:IB}) the bursting
behaviour is diminished but the currents needed to get firing are still high. As a
result I decreased the leak conductance by a factor of 10 to 0.01 as seen in the
upper right of Figure \ref{fig:IB}. This is the model that I used for the sensitivity
analysis and modelling of Kv1.1 mutations. However, when the original IB model has a
reduced leak current (of 0.01) it bursts and only for a small current range (see upper
left of Figure \ref{fig:IB}).
** Issue:
Which model to use? To use the model with reduced leak that has nice properties with
Kv1.1 added, the bursting and weird fI curve of the model without Kv1.1 needs to be
addressed (bursting is not well captured by the analysis methods). To use the model with
the large leak current (the original model), the large input currents is concerning and
the sensitivity analysis and Kv1.1 mutation modelling would need to be re-done for this
model with and without Kv1.1 (with 20/24 cores on the Kraken this would take 2-3 days
I think). Alternatively, as neither option really sits well with me, we could remove this
model from all figure and discussion and focus on the other models that in their
original states (and with Kv1.1 added) have repetitive firing without bursting.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=15cm]{IB_issue_plot.pdf}
\caption{The fI curves and exampling spike trains from the IB model with different
Leak conductances without and with (+Kv1.1) Kv1.1 conductance.}
\label{fig:IB}
\end{figure}
#+END_EXPORT
* Rheobase Sensitivity Analysis:
I am not yet happy with this figure's layout
** Question figure addresses:
How is rheobase affected by changes in current properties across models? Is the change
in rheobase always in the same direction across models?
** Method by which data is generated:
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the fI curves computed. From this fI curve the
largest injected current at which no firing occurs and the smallest injected
current at which firing occurs were obtained. This current interval was then simulated
to obtain the rheobase at greater resolution.
** Conclusion from Figure:
Generally the effect on rheobase is similar across all models/current environments
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{rheobase_correlation.pdf}
\caption{}
\label{fig:rheo}
\end{figure}
#+END_EXPORT
* AUC Sensitivity Analysis:
I prefer the first layout
** Question figure addresses:
How is AUC affected by changes in current properties across models? Is the change
in AUC rheobase always in the same direction across models?
** Method by which data is generated:
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the steady-state fI curves computed. From this fI
curve the largest injected current at which no firing occurs was obtained and the
integral from this current using the composite trapezoidal rule for 1/5 of the current
range.
** Conclusion from Figure:
A given current property change does not necessarily cause the same
change in rheobase and as such the outcome of a given change is dependent on the
current environment or cell type.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{AUC_correlation.pdf}
\caption{}
\label{fig:AUC}
\end{figure}
#+END_EXPORT
* Kv1.1 mutation simulation:
** Question figure addresses:
Do mutations of Kv1.1 cause similar effects on firing across cell types or is the effect
cell type (and thus neuronal network) dependent?
** Method by which data is generated:
Published Kv1.1 mutations (Lauxmann et al 2021) are simulated in all models containing
Kv1.1 or an inactivating K^+ current by altering the current properties according to
those experimentally measured for each mutation. The firing of each model for each
mutation are then simulated and the rheobase and AUC are computed.
** Conclusion from Figure:
The effects of Kv1.1 mutations on rheobase are highly correlated across models indicating
that these mutations affect the rheobase in a similar fashion. However, the effect of
Kv1.1 mutations vary across models as seen by the different correlation magnitudes
between models. Thus although these mutations affect rheobase in a similar manner, the
effect on AUC cannot easily be generalized and depends on cell type.
Furthermore, this Figure demonstrates why characterization of mutations in terms of
LOF or GOF in relation to firing overlooks potentially important characteristics of
the changes in firing seen in different cell types. Thus, the characterization LOF
and GOF is useful at a channel level to characterize the effects of a mutation on
the current, but cannot and should not be blindly extended to characterize the
effects of the mutation on firing as LOF and GOF, not only because the current
environment in which this mutation occurs is a key determinant of the firing outcome,
but also that firing is complex and not easily characterized as LOF or GOF.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{simulation_model_comparison.pdf}
\caption{}
\label{fig:kv11}
\end{figure}
#+END_EXPORT
* Ramp Firing - For Supplements?:
** Question figure addresses:
How does the firing of the models look like with a ramp protocol?
** Method by which data is generated:
A 4 second ramp with the same current range as the step currents used to obtain fI
plots is used and the firing of all models is simulated. The resulting spike trains
are plotted.
** Conclusion from Figure:
The diversity of firing seen with step currents is also seen with current ramps. The
ramps highlight the hysteresis in models.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=20cm]{ramp_firing.pdf}
\caption{A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+
current for Kv1.1.}
\label{fig:ramp}
\end{figure}
#+END_EXPORT

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# Instructions for org mode export
# - to get export options: ctrl-c ctrl-e
# - to export as latex pdf: ctrl-c ctrl-e l p
#+OPTIONS: ':nil *:nil -:t ::t <:t H:3 \n:nil ^:t arch:headline
#+OPTIONS: author:nil broken-links:nil c:nil creator:nil
#+OPTIONS: d:(not "LOGBOOK") date:nil e:t email:nil f:t inline:t num:nil
#+OPTIONS: p:nil pri:nil prop:nil stat:t tags:t tasks:t tex:t
#+OPTIONS: timestamp:t title:nil toc:nil todo:nil |:t
#+TITLE: Nils Koch
#+DATE: <2021-08-16 Mon>
#+EMAIL: nils.koch@mail.mcgill.ca
#+TAGS: noexport(n)
#+LATEX_CLASS: article
#+LATEX_CLASS_OPTIONS: [letterpaper,10pt]
#+LATEX_HEADER: \usepackage[margin=0.6in]{geometry}
#+LATEX_HEADER: \usepackage{fontawesome}
#+LATEX_HEADER: \usepackage{titling}
#+LATEX_HEADER: \usepackage{titlesec}
#+LATEX_HEADER: \usepackage{fancyhdr}
#+LATEX_HEADER: \usepackage{setspace}
#+LATEX_HEADER: \usepackage{xcolor}
#+LATEX_HEADER: \usepackage{tabularx,xspace}
#+LATEX_HEADER: \usepackage{url}
#+LATEX_HEADER: \usepackage{academicons}
#+LATEX_HEADER: \usepackage{float}
#+LATEX_HEADER: \usepackage{hyperref}
#+LATEX_HEADER: \parindent=0in
#+LATEX_HEADER: \def\refname{\large References}
#+LATEX_HEADER: \newcommand{\eg}{e.g.\ }
#+LATEX_HEADER: \newcommand{\ie}{i.e.,\xspace }
#+LATEX_HEADER: \newcommand{\Aref}[1]{[A\ref{it:#1}]}
#+LATEX_HEADER: \newcommand{\Cref}[1]{[C\ref{it:#1}]}
#+LATEX_HEADER: \newcommand{\Pref}[1]{[P\ref{it:#1}]}
#+LATEX_HEADER: \usepackage{academicons}
#+LATEX_HEADER: \usepackage[breaklinks=true]{hyperref}
#+LATEX_HEADER: \usepackage{graphicx}
#+LATEX_HEADER: \usepackage{graphbox}
#+LATEX_HEADER: \usepackage{matlab-prettifier}
#+LATEX_HEADER: \usepackage[scaled]{helvet} \renewcommand\familydefault{\sfdefault}
#+LATEX_HEADER: \graphicspath{{./Figures/}}
#+LATEX_HEADER_EXTRA:
# For citation colors
#+LATEX_HEADER_EXTRA: \hypersetup{
#+LATEX_HEADER_EXTRA: colorlinks,
#+LATEX_HEADER_EXTRA: linkcolor={red!50!black},
#+LATEX_HEADER_EXTRA: citecolor={blue!50!black},
#+LATEX_HEADER_EXTRA: urlcolor={black!70}
#+LATEX_HEADER_EXTRA: }
#+DESCRIPTION:
#+KEYWORDS:
#+subtitle:
#+LATEX_COMPILER: pdflatex
#+BEGIN_EXPORT latex
\renewcommand{\maketitle}
\maketitle{
\begin{center}
\Huge \textbf{Update on Figures}}}\\
\end{center}
}
%\thispagestyle{empty} %remove header on first page
\titleformat{\section}{\Large\bfseries}{\thesection}{0pt}{}
\titleformat{\subsection}{\large\bfseries}{\thesection}{0pt}{}
\titlespacing*{\section}{0pt}{0ex}{0ex}
\titlespacing*{\subsection}{0pt}{0ex}{0ex}
\titlespacing*{\itemsep}{0pt}{0ex}{0ex}
\pagestyle{fancy}
\fancyhf{}
\renewcommand{\headrulewidth}{0pt} % remove lines as well
\renewcommand{\footrulewidth}{0pt} % remove lines as well
%\lfoot{\textcolor{black!50}{\footnotesize \today}}
%\cfoot{\textcolor{black!50}{\footnotesize Nils Koch }}
\rfoot{\textcolor{black!50}{\thepage}}
%\lhead{}
\chead{\today}
%\rhead{}
\newcommand{\squishlist}{
\begin{list}{$\bullet$}
{ \setlength{\itemsep}{0pt} \setlength{\parsep}{3pt} \setlength{\topsep}{3pt} \setlength{\partopsep}{0pt}
\setlength{\leftmargin}{1.5em} \setlength{\labelwidth}{1em} \setlength{\labelsep}{0.5em} } }
\newcommand{\squishend}{\end{list} }
#+END_EXPORT
* Firing Characterization:
** Question figure addresses:
Firing is a complicated phenomenon. How can it be simply characterized to compare the
effects of changes in current properties?
** Method by which data is generated:
Schematic diagram that does not contain underlying data - contains different square
root functions.
** Conclusion from Figure:
Firing can be characterized by the rheobase and the AUC (proprotional to the increase in
firing after the rheobase). The rheobase and firing in a small range above it (AUC) are
likely important for determining network excitability (I think this makes sense,
would need references to support this).
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=10cm]{firing_characterization.pdf}
\caption{A. Demonstrates AUC in cyan. B. Demonstrates what combinations of increased and
decreased rheobase and AUC look like in terms of fI curves.}
\label{fig:firing_charact}
\end{figure}
#+END_EXPORT
* Diversity in Model Firing:
We have used a number of neuronal models that do not burst to look at the effects
of changes in current properties in firing given different cell types/current
environments
** Question figure addresses:
Which model is used?
** Rationale:
The effect of a change in a current property cannot be assessed in only one cell
type to understand the general effects of this change and to assess whether differences
occur across cell types.
** Method by which data is generated:
Models from different sources are used and an example spike train is shown for each model
along with a fI curve. The black dot on the fI curve indicates where the spike train is
taken from and the green and red dots indicate the current at which the first and last
spike occurs from an increasing and decreasing current ramp respectively. (These ramps
can be seen in the ramp figure at the end).
** Conclusion from Figure:
The models use are diverse and display a variety of spike shapes, firing behaviours, and
fI curve shapes.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{diversity_in_firing.pdf}
\caption{Spike trains and corresponding fI curves from: A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+ current for Kv1.1. The black
dot on the fI curve indicates where the spike train is taken from and the green and red
dots indicate the current at which the first and last spike occurs from an increasing and
decreasing current ramp respectively.}
\label{fig:div_firing}
\end{figure}
#+END_EXPORT
* IB model issue: :noexport:
** Issue Background:
IB (intrinsicially bursting) model from Pospischil et al. 2008 uses a leak conductance
of 0.1. This results in bursting like firing initially (see bottom right of Figure
\ref{fig:IB}) and requires large currents to be injected (> 0.75 nA). When the Kv1.1
current is added to this model (bottom right Figure \ref{fig:IB}) the bursting
behaviour is diminished but the currents needed to get firing are still high. As a
result I decreased the leak conductance by a factor of 10 to 0.01 as seen in the
upper right of Figure \ref{fig:IB}. This is the model that I used for the sensitivity
analysis and modelling of Kv1.1 mutations. However, when the original IB model has a
reduced leak current (of 0.01) it bursts and only for a small current range (see upper
left of Figure \ref{fig:IB}).
** Issue:
Which model to use? To use the model with reduced leak that has nice properties with
Kv1.1 added, the bursting and weird fI curve of the model without Kv1.1 needs to be
addressed (bursting is not well captured by the analysis methods). To use the model with
the large leak current (the original model), the large input currents is concerning and
the sensitivity analysis and Kv1.1 mutation modelling would need to be re-done for this
model with and without Kv1.1 (with 20/24 cores on the Kraken this would take 2-3 days
I think). Alternatively, as neither option really sits well with me, we could remove this
model from all figure and discussion and focus on the other models that in their
original states (and with Kv1.1 added) have repetitive firing without bursting.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=15cm]{IB_issue_plot.pdf}
\caption{The fI curves and exampling spike trains from the IB model with different
Leak conductances without and with (+Kv1.1) Kv1.1 conductance.}
\label{fig:IB}
\end{figure}
#+END_EXPORT
* Rheobase Sensitivity Analysis:
I am not yet happy with this figure's layout
** Question figure addresses:
How is rheobase affected by changes in current properties across models? Is the change
in rheobase always in the same direction across models?
** Method by which data is generated:
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the fI curves computed. From this fI curve the
largest injected current at which no firing occurs and the smallest injected
current at which firing occurs were obtained. This current interval was then simulated
to obtain the rheobase at greater resolution.
** Conclusion from Figure:
Generally the effect on rheobase is similar across all models/current environments
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{rheobase_correlation.pdf}
\caption{}
\label{fig:rheo}
\end{figure}
#+END_EXPORT
* AUC Sensitivity Analysis:
I prefer the first layout
** Question figure addresses:
How is AUC affected by changes in current properties across models? Is the change
in AUC rheobase always in the same direction across models?
** Method by which data is generated:
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the steady-state fI curves computed. From this fI
curve the largest injected current at which no firing occurs was obtained and the
integral from this current using the composite trapezoidal rule for 1/5 of the current
range.
** Conclusion from Figure:
A given current property change does not necessarily cause the same
change in rheobase and as such the outcome of a given change is dependent on the
current environment or cell type.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{AUC_correlation.pdf}
\caption{}
\label{fig:AUC}
\end{figure}
#+END_EXPORT
* Kv1.1 mutation simulation:
** Question figure addresses:
Do mutations of Kv1.1 cause similar effects on firing across cell types or is the effect
cell type (and thus neuronal network) dependent?
** Method by which data is generated:
Published Kv1.1 mutations (Lauxmann et al 2021) are simulated in all models containing
Kv1.1 or an inactivating K^+ current by altering the current properties according to
those experimentally measured for each mutation. The firing of each model for each
mutation are then simulated and the rheobase and AUC are computed.
** Conclusion from Figure:
The effects of Kv1.1 mutations on rheobase are highly correlated across models indicating
that these mutations affect the rheobase in a similar fashion. However, the effect of
Kv1.1 mutations vary across models as seen by the different correlation magnitudes
between models. Thus although these mutations affect rheobase in a similar manner, the
effect on AUC cannot easily be generalized and depends on cell type.
Furthermore, this Figure demonstrates why characterization of mutations in terms of
LOF or GOF in relation to firing overlooks potentially important characteristics of
the changes in firing seen in different cell types. Thus, the characterization LOF
and GOF is useful at a channel level to characterize the effects of a mutation on
the current, but cannot and should not be blindly extended to characterize the
effects of the mutation on firing as LOF and GOF, not only because the current
environment in which this mutation occurs is a key determinant of the firing outcome,
but also that firing is complex and not easily characterized as LOF or GOF.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{simulation_model_comparison.pdf}
\caption{}
\label{fig:kv11}
\end{figure}
#+END_EXPORT
* Ramp Firing - For Supplements?:
** Question figure addresses:
How does the firing of the models look like with a ramp protocol?
** Method by which data is generated:
A 4 second ramp with the same current range as the step currents used to obtain fI
plots is used and the firing of all models is simulated. The resulting spike trains
are plotted.
** Conclusion from Figure:
The diversity of firing seen with step currents is also seen with current ramps. The
ramps highlight the hysteresis in models.
#+BEGIN_EXPORT latex
\begin{figure}[H]
\includegraphics[align=c,width=20cm]{ramp_firing.pdf}
\caption{A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+
current for Kv1.1.}
\label{fig:ramp}
\end{figure}
#+END_EXPORT

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% Created 2022-02-16 Wed 15:42
% Intended LaTeX compiler: pdflatex
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\date{}
\title{Nils Koch}
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\begin{center}
\Huge \textbf{Update on Figures}}}\\
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%\thispagestyle{empty} %remove header on first page
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\titleformat{\subsection}{\large\bfseries}{\thesection}{0pt}{}
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\section*{Firing Characterization:}
\label{sec:orgefc49e8}
\subsection*{Question figure addresses:}
\label{sec:org08ca3c5}
Firing is a complicated phenomenon. How can it be simply characterized to compare the
effects of changes in current properties?
\subsection*{Method by which data is generated:}
\label{sec:org68edbd3}
Schematic diagram that does not contain underlying data - contains different square
root functions.
\subsection*{Conclusion from Figure:}
\label{sec:org320d05e}
Firing can be characterized by the rheobase and the AUC (proprotional to the increase in
firing after the rheobase). The rheobase and firing in a small range above it (AUC) are
likely important for determining network excitability (I think this makes sense,
would need references to support this).
\begin{figure}[H]
\includegraphics[align=c,width=10cm]{firing_characterization.pdf}
\caption{A. Demonstrates AUC in cyan. B. Demonstrates what combinations of increased and
decreased rheobase and AUC look like in terms of fI curves.}
\label{fig:firing_charact}
\end{figure}
\section*{Diversity in Model Firing:}
\label{sec:org411197c}
We have used a number of neuronal models that do not burst to look at the effects
of changes in current properties in firing given different cell types/current
environments
\subsection*{Question figure addresses:}
\label{sec:orge37c0bb}
Which model is used?
\subsection*{Rationale:}
\label{sec:orga9c3a57}
The effect of a change in a current property cannot be assessed in only one cell
type to understand the general effects of this change and to assess whether differences
occur across cell types.
\subsection*{Method by which data is generated:}
\label{sec:orga107703}
Models from different sources are used and an example spike train is shown for each model
along with a fI curve. The black dot on the fI curve indicates where the spike train is
taken from and the green and red dots indicate the current at which the first and last
spike occurs from an increasing and decreasing current ramp respectively. (These ramps
can be seen in the ramp figure at the end).
\subsection*{Conclusion from Figure:}
\label{sec:org8a15a73}
The models use are diverse and display a variety of spike shapes, firing behaviours, and
fI curve shapes.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{diversity_in_firing.pdf}
\caption{Spike trains and corresponding fI curves from: A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+ current for Kv1.1. The black
dot on the fI curve indicates where the spike train is taken from and the green and red
dots indicate the current at which the first and last spike occurs from an increasing and
decreasing current ramp respectively.}
\label{fig:div_firing}
\end{figure}
\section*{Rheobase Sensitivity Analysis:}
\label{sec:org1e03320}
I am not yet happy with this figure's layout
\subsection*{Question figure addresses:}
\label{sec:org696855b}
How is rheobase affected by changes in current properties across models? Is the change
in rheobase always in the same direction across models?
\subsection*{Method by which data is generated:}
\label{sec:org09129b8}
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the fI curves computed. From this fI curve the
largest injected current at which no firing occurs and the smallest injected
current at which firing occurs were obtained. This current interval was then simulated
to obtain the rheobase at greater resolution.
\subsection*{Conclusion from Figure:}
\label{sec:orga1ee38f}
Generally the effect on rheobase is similar across all models/current environments
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{rheobase_correlation.pdf}
\caption{}
\label{fig:rheo}
\end{figure}
\section*{AUC Sensitivity Analysis:}
\label{sec:orgea61060}
I prefer the first layout
\subsection*{Question figure addresses:}
\label{sec:org73643ea}
How is AUC affected by changes in current properties across models? Is the change
in AUC rheobase always in the same direction across models?
\subsection*{Method by which data is generated:}
\label{sec:org4e1eb8f}
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the steady-state fI curves computed. From this fI
curve the largest injected current at which no firing occurs was obtained and the
integral from this current using the composite trapezoidal rule for 1/5 of the current
range.
\subsection*{Conclusion from Figure:}
\label{sec:org8eb1892}
A given current property change does not necessarily cause the same
change in rheobase and as such the outcome of a given change is dependent on the
current environment or cell type.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{AUC_correlation.pdf}
\caption{}
\label{fig:AUC}
\end{figure}
\section*{Kv1.1 mutation simulation:}
\label{sec:org095a1ae}
\subsection*{Question figure addresses:}
\label{sec:org12e9ebc}
Do mutations of Kv1.1 cause similar effects on firing across cell types or is the effect
cell type (and thus neuronal network) dependent?
\subsection*{Method by which data is generated:}
\label{sec:org094b162}
Published Kv1.1 mutations (Lauxmann et al 2021) are simulated in all models containing
Kv1.1 or an inactivating K\^{}+ current by altering the current properties according to
those experimentally measured for each mutation. The firing of each model for each
mutation are then simulated and the rheobase and AUC are computed.
\subsection*{Conclusion from Figure:}
\label{sec:orgd0738e2}
The effects of Kv1.1 mutations on rheobase are highly correlated across models indicating
that these mutations affect the rheobase in a similar fashion. However, the effect of
Kv1.1 mutations vary across models as seen by the different correlation magnitudes
between models. Thus although these mutations affect rheobase in a similar manner, the
effect on AUC cannot easily be generalized and depends on cell type.
Furthermore, this Figure demonstrates why characterization of mutations in terms of
LOF or GOF in relation to firing overlooks potentially important characteristics of
the changes in firing seen in different cell types. Thus, the characterization LOF
and GOF is useful at a channel level to characterize the effects of a mutation on
the current, but cannot and should not be blindly extended to characterize the
effects of the mutation on firing as LOF and GOF, not only because the current
environment in which this mutation occurs is a key determinant of the firing outcome,
but also that firing is complex and not easily characterized as LOF or GOF.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{simulation_model_comparison.pdf}
\caption{}
\label{fig:kv11}
\end{figure}
\section*{Ramp Firing - For Supplements?:}
\label{sec:orge8a0957}
\subsection*{Question figure addresses:}
\label{sec:org46e89c4}
How does the firing of the models look like with a ramp protocol?
\subsection*{Method by which data is generated:}
\label{sec:org878a189}
A 4 second ramp with the same current range as the step currents used to obtain fI
plots is used and the firing of all models is simulated. The resulting spike trains
are plotted.
\subsection*{Conclusion from Figure:}
\label{sec:org22fe40d}
The diversity of firing seen with step currents is also seen with current ramps. The
ramps highlight the hysteresis in models.
\begin{figure}[H]
\includegraphics[align=c,width=20cm]{ramp_firing.pdf}
\caption{A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+
current for Kv1.1.}
\label{fig:ramp}
\end{figure}
\end{document}

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% Created 2022-02-16 Wed 15:41
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\Huge \textbf{Update on Figures}}}\\
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\section*{Firing Characterization:}
\label{sec:org2ff19f9}
\subsection*{Question figure addresses:}
\label{sec:org39e44a3}
Firing is a complicated phenomenon. How can it be simply characterized to compare the
effects of changes in current properties?
\subsection*{Method by which data is generated:}
\label{sec:org8f27edf}
Schematic diagram that does not contain underlying data - contains different square
root functions.
\subsection*{Conclusion from Figure:}
\label{sec:org219d22f}
Firing can be characterized by the rheobase and the AUC (proprotional to the increase in
firing after the rheobase). The rheobase and firing in a small range above it (AUC) are
likely important for determining network excitability (I think this makes sense,
would need references to support this).
\begin{figure}[H]
\includegraphics[align=c,width=10cm]{firing_characterization.pdf}
\caption{A. Demonstrates AUC in cyan. B. Demonstrates what combinations of increased and
decreased rheobase and AUC look like in terms of fI curves.}
\label{fig:firing_charact}
\end{figure}
\section*{Diversity in Model Firing:}
\label{sec:org2d2ab53}
We have used a number of neuronal models that do not burst to look at the effects
of changes in current properties in firing given different cell types/current
environments
\subsection*{Question figure addresses:}
\label{sec:org2a68d8a}
Which model is used?
\subsection*{Rationale:}
\label{sec:org574a416}
The effect of a change in a current property cannot be assessed in only one cell
type to understand the general effects of this change and to assess whether differences
occur across cell types.
\subsection*{Method by which data is generated:}
\label{sec:orgf4eccc9}
Models from different sources are used and an example spike train is shown for each model
along with a fI curve. The black dot on the fI curve indicates where the spike train is
taken from and the green and red dots indicate the current at which the first and last
spike occurs from an increasing and decreasing current ramp respectively. (These ramps
can be seen in the ramp figure at the end).
\subsection*{Conclusion from Figure:}
\label{sec:org2b1b0e7}
The models use are diverse and display a variety of spike shapes, firing behaviours, and
fI curve shapes.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{diversity_in_firing.pdf}
\caption{Spike trains and corresponding fI curves from: A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+ current for Kv1.1. The black
dot on the fI curve indicates where the spike train is taken from and the green and red
dots indicate the current at which the first and last spike occurs from an increasing and
decreasing current ramp respectively.}
\label{fig:div_firing}
\end{figure}
\section*{Rheobase Sensitivity Analysis:}
\label{sec:org482a6cf}
I am not yet happy with this figure's layout
\subsection*{Question figure addresses:}
\label{sec:org8d09846}
How is rheobase affected by changes in current properties across models? Is the change
in rheobase always in the same direction across models?
\subsection*{Method by which data is generated:}
\label{sec:org679728a}
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the fI curves computed. From this fI curve the
largest injected current at which no firing occurs and the smallest injected
current at which firing occurs were obtained. This current interval was then simulated
to obtain the rheobase at greater resolution.
\subsection*{Conclusion from Figure:}
\label{sec:orgab5a050}
Generally the effect on rheobase is similar across all models/current environments
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{rheobase_correlation.pdf}
\caption{}
\label{fig:rheo}
\end{figure}
\section*{AUC Sensitivity Analysis:}
\label{sec:org84023d3}
I prefer the first layout
\subsection*{Question figure addresses:}
\label{sec:org2aedc23}
How is AUC affected by changes in current properties across models? Is the change
in AUC rheobase always in the same direction across models?
\subsection*{Method by which data is generated:}
\label{sec:org7f21d20}
A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
to all or most models, where one current property was changed systematically at a time,
the firing responses simulated and the steady-state fI curves computed. From this fI
curve the largest injected current at which no firing occurs was obtained and the
integral from this current using the composite trapezoidal rule for 1/5 of the current
range.
\subsection*{Conclusion from Figure:}
\label{sec:org2c7ad14}
A given current property change does not necessarily cause the same
change in rheobase and as such the outcome of a given change is dependent on the
current environment or cell type.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{AUC_correlation.pdf}
\caption{}
\label{fig:AUC}
\end{figure}
\section*{Kv1.1 mutation simulation:}
\label{sec:org747834c}
\subsection*{Question figure addresses:}
\label{sec:orgcae797a}
Do mutations of Kv1.1 cause similar effects on firing across cell types or is the effect
cell type (and thus neuronal network) dependent?
\subsection*{Method by which data is generated:}
\label{sec:org58691da}
Published Kv1.1 mutations (Lauxmann et al 2021) are simulated in all models containing
Kv1.1 or an inactivating K\^{}+ current by altering the current properties according to
those experimentally measured for each mutation. The firing of each model for each
mutation are then simulated and the rheobase and AUC are computed.
\subsection*{Conclusion from Figure:}
\label{sec:org4808be0}
The effects of Kv1.1 mutations on rheobase are highly correlated across models indicating
that these mutations affect the rheobase in a similar fashion. However, the effect of
Kv1.1 mutations vary across models as seen by the different correlation magnitudes
between models. Thus although these mutations affect rheobase in a similar manner, the
effect on AUC cannot easily be generalized and depends on cell type.
Furthermore, this Figure demonstrates why characterization of mutations in terms of
LOF or GOF in relation to firing overlooks potentially important characteristics of
the changes in firing seen in different cell types. Thus, the characterization LOF
and GOF is useful at a channel level to characterize the effects of a mutation on
the current, but cannot and should not be blindly extended to characterize the
effects of the mutation on firing as LOF and GOF, not only because the current
environment in which this mutation occurs is a key determinant of the firing outcome,
but also that firing is complex and not easily characterized as LOF or GOF.
\begin{figure}[H]
\includegraphics[align=c,width=18cm]{simulation_model_comparison.pdf}
\caption{}
\label{fig:kv11}
\end{figure}
\section*{Ramp Firing - For Supplements?:}
\label{sec:orgde070fe}
\subsection*{Question figure addresses:}
\label{sec:org86a05b7}
How does the firing of the models look like with a ramp protocol?
\subsection*{Method by which data is generated:}
\label{sec:org4560e37}
A 4 second ramp with the same current range as the step currents used to obtain fI
plots is used and the firing of all models is simulated. The resulting spike trains
are plotted.
\subsection*{Conclusion from Figure:}
\label{sec:orgdda18ae}
The diversity of firing seen with step currents is also seen with current ramps. The
ramps highlight the hysteresis in models.
\begin{figure}[H]
\includegraphics[align=c,width=20cm]{ramp_firing.pdf}
\caption{A. Cb stellate, B. RS Inhibitory,
C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+
current for Kv1.1.}
\label{fig:ramp}
\end{figure}
\end{document}

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@Comment{$ biblatex control file $}
@Comment{$ biblatex bcf format version 3.7 $}
% Do not modify this file!
%
% This is an auxiliary file used by the 'biblatex' package.
% This file may safely be deleted. It will be recreated as
% required.
@Control{biblatex-control,
options = {3.7:0:0:1:0:1:1:0:0:0:0:0:3:1:3:1:0:0:3:1:79:+:+:none},
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#+TITLE: Figure update
#+AUTHOR: Nils Koch
#+DATE:
#+startup: beamer
#+BEAMER_THEME: Boadilla
#+COLUMNS: %45ITEM %10BEAMER_env(Env) %10BEAMER_act(Act) %4BEAMER_col(Col) %8BEAMER_opt(Opt)
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#+COLUMNS: %40ITEM %10BEAMER_env(Env) %9BEAMER_envargs(Env Args) %4BEAMER_col(Col) %10BEAMER_extra(Extra)
#+BEAMER_HEADER: \subtitle{}
# '+BEAMER_HEADER: \AtBeginSection[]{\begin{frame}<beamer>\frametitle{\secname}\end{frame}}
#+TAGS: noexport(n)
# 'Use Next line for 16:9
# '+LATEX_HEADER: \usepackage[orientation=landscape,size=custom,width=16,height=9.75,scale=0.5,debug]{beamerposter}
#+LaTeX_HEADER:\usepackage[backend=bibtex,sorting=none, style=numeric-comp, citestyle=numeric-comp]{biblatex}
#+LATEX_HEADER: \usepackage{endnotes}
#+LaTeX_HEADER:\bibliography{H2v01.bib} %% point at your bib file
#+LaTeX_CLASS: beamer
#+LaTeX_CLASS_OPTIONS: [presentation]
#+LATEX_HEADER: \usepackage{tikz,bm}
#+LATEX_HEADER: \usepackage{epstopdf}
#+LATEX_HEADER: \graphicspath{{../Figures/}}
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#+LATEX_HEADER: \setbeamercolor{title}{fg=mcgillred}
#+LATEX_HEADER: \setbeamercolor{frametitle}{fg=mcgillred}
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#+LATEX_HEADER: \setbeamercolor{block title}{bg=mcgillred,fg=white}
#+LATEX_HEADER: \setbeamerfont{title}{size=\Large, series=\bfseries}
#+LATEX_HEADER: \setbeamercolor{alerted text}{fg=black}
#+LATEX_HEADER: \setbeamerfont{alerted text}{series=\bfseries}
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#+LATEX_HEADER: \setbeamertemplate{caption}{\raggedright\insertcaption\par}
#+LATEX_HEADER: \setbeamerfont{caption}{size=\tiny}
#+LATEX_HEADER: \setlength\abovecaptionskip{-5pt}
#+LATEX_HEADER: \renewcommand{\footnote}{\endnote}
#+LATEX_HEADER: \usepackage{animate}
# +END_EXPORT
* Introduction
*** Intro to org to Beamer
- This is not that visually appealling, but I haven't taken the time to set the colors and style to my liking in the Latex header
- I have tried to include as many examples of things I find useful as possible
- sometimes this makes the slide not make much sense, but the example of how to do things is hopefully useful
- The only slight pain with using org for both Beamer and normal Latex pdf is:
- you cannot have the pdf open in some pdf viewers and export to it (eg adobe)
- I use Sumatra (https://www.sumatrapdfreader.org/free-pdf-reader)
- can have your pdf open in sumatra, export to it and it will update the pdf to the new exported file while open
*** Slide not exported :noexport:
- This slide is not exported when the noexport tag is present
- to remove the tag: ctrl-c crtl-q space enter
- to add a noexport tag: ctrl-x ctrl-q n enter
- this can be very useful if you have a comprehensive slide set and you only want to present some slides or sections
- this can also be done on sections (e.g. * Introduction)
* Figure update
*** Firing Characterization
\vspace{-0.5cm}
**** Col left :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.65
:BEAMER_opt: [t]
:END:
- Firing is a complicated phenomenon
- How to best characterize it?
- rheobase
- AUC
**** Col right :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.35
:BEAMER_opt: [t]
:END:
#+ATTR_LATEX: :width 0.95\textwidth
[[file:firing_characterization.pdf]]
*** Diversity in Firing Properties of the Models
#+ATTR_LATEX: :width 0.55\textwidth
[[file:diversity_in_firing.pdf]]
*** Sensitivy analysis: OFAT
\vspace{-2cm}
- [ ] one factor at a time sensitivity analysis
- simulate firing responses
- compute fI curves
- get rheobase
- compute AUC
*** Rheobase sensitivity Analysis
#+ATTR_LATEX: :width 0.85\textwidth
[[file:rheobase_correlation.pdf]]
\tiny Koch et al. 2022
*** AUC Sensitivity Analysis
- AUC = area under the curve
#+ATTR_LATEX: :width 0.75\textwidth
[[file:AUC_correlation.pdf]]
- AUC over the initial non-zero fI curve is a proxy for slope
*** \(K_V1.1\) Mutations
#+ATTR_LATEX: :width 0.95\textwidth
[[file:simulation_model_comparison.pdf]]
*** Ramp Firing
#+ATTR_LATEX: :width 0.95\textwidth
[[file:ramp_firing.pdf]]

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% Created 2022-02-16 Wed 15:43
% Intended LaTeX compiler: pdflatex
\documentclass[presentation]{beamer}
\usepackage[utf8]{inputenc}
\usepackage[T1]{fontenc}
\usepackage{graphicx}
\usepackage{grffile}
\usepackage{longtable}
\usepackage{wrapfig}
\usepackage{rotating}
\usepackage[normalem]{ulem}
\usepackage{amsmath}
\usepackage{textcomp}
\usepackage{amssymb}
\usepackage{capt-of}
\usepackage{hyperref}
\usepackage[backend=bibtex,sorting=none, style=numeric-comp, citestyle=numeric-comp]{biblatex}
\usepackage{endnotes}
\bibliography{H2v01.bib} %% point at your bib file
\usepackage{tikz,bm}
\usepackage{epstopdf}
\graphicspath{{../Figures/}}
\definecolor{mcgillred}{RGB}{237, 27, 47}
\definecolor{darkred}{RGB}{158,9,24}
\definecolor{palegray}{RGB}{244,244,244}
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\setbeamerfont{title}{size=\Large, series=\bfseries}
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\newcommand{\nox}{\(\mathrm{NO_{x}}\)}
\newlength\figH
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\setlength\abovecaptionskip{-5pt}
\renewcommand{\footnote}{\endnote}
\usepackage{animate}
\usetheme{Boadilla}
\author{Nils Koch}
\date{}
\title{Figure update}
\subtitle{}
\hypersetup{
pdfauthor={Nils Koch},
pdftitle={Figure update},
pdfkeywords={},
pdfsubject={},
pdfcreator={Emacs 27.2 (Org mode 9.4.4)},
pdflang={English}}
\begin{document}
\maketitle
\section{Introduction}
\label{sec:orgaa79910}
\begin{frame}[label={sec:org5e30c84}]{Intro to org to Beamer}
\begin{itemize}
\item This is not that visually appealling, but I haven't taken the time to set the colors and style to my liking in the Latex header
\item I have tried to include as many examples of things I find useful as possible
\begin{itemize}
\item sometimes this makes the slide not make much sense, but the example of how to do things is hopefully useful
\end{itemize}
\item The only slight pain with using org for both Beamer and normal Latex pdf is:
\begin{itemize}
\item you cannot have the pdf open in some pdf viewers and export to it (eg adobe)
\item I use Sumatra (\url{https://www.sumatrapdfreader.org/free-pdf-reader})
\begin{itemize}
\item can have your pdf open in sumatra, export to it and it will update the pdf to the new exported file while open
\end{itemize}
\end{itemize}
\end{itemize}
\end{frame}
\section{Figure update}
\label{sec:orgf0c258a}
\begin{frame}[label={sec:orgbc00e40}]{Firing Characterization}
\vspace{-0.5cm}
\begin{columns}
\begin{column}[t]{0.65\columnwidth}
\begin{itemize}
\item Firing is a complicated phenomenon
\item How to best characterize it?
\begin{itemize}
\item rheobase
\item AUC
\end{itemize}
\end{itemize}
\end{column}
\begin{column}[t]{0.35\columnwidth}
\begin{center}
\includegraphics[width=0.95\textwidth]{firing_characterization.pdf}
\end{center}
\end{column}
\end{columns}
\end{frame}
\begin{frame}[label={sec:org30ceea9}]{Diversity in Firing Properties of the Models}
\begin{center}
\includegraphics[width=0.55\textwidth]{diversity_in_firing.pdf}
\end{center}
\end{frame}
\begin{frame}[label={sec:org2ecf870}]{Sensitivy analysis: OFAT}
\vspace{-2cm}
\begin{itemize}
\item[{$\square$}] one factor at a time sensitivity analysis
\item simulate firing responses
\begin{itemize}
\item compute fI curves
\begin{itemize}
\item get rheobase
\item compute AUC
\end{itemize}
\end{itemize}
\end{itemize}
\end{frame}
\begin{frame}[label={sec:orgd668fd1}]{Rheobase sensitivity Analysis}
\begin{center}
\includegraphics[width=0.85\textwidth]{rheobase_correlation.pdf}
\end{center}
\tiny Koch et al. 2022
\end{frame}
\begin{frame}[label={sec:orgb070147}]{AUC Sensitivity Analysis}
\begin{itemize}
\item AUC = area under the curve
\end{itemize}
\begin{center}
\includegraphics[width=0.75\textwidth]{AUC_correlation.pdf}
\end{center}
\begin{itemize}
\item AUC over the initial non-zero fI curve is a proxy for slope
\end{itemize}
\end{frame}
\begin{frame}[label={sec:orgb9500d1}]{\(K_V1.1\) Mutations}
\begin{center}
\includegraphics[width=0.95\textwidth]{simulation_model_comparison.pdf}
\end{center}
\end{frame}
\begin{frame}[label={sec:orga5c8265}]{Ramp Firing}
\begin{center}
\includegraphics[width=0.95\textwidth]{ramp_firing.pdf}
\end{center}
\end{frame}
\end{document}

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% Created 2022-02-16 Wed 15:40
% Intended LaTeX compiler: pdflatex
\documentclass[presentation]{beamer}
\usepackage[utf8]{inputenc}
\usepackage[T1]{fontenc}
\usepackage{graphicx}
\usepackage{grffile}
\usepackage{longtable}
\usepackage{wrapfig}
\usepackage{rotating}
\usepackage[normalem]{ulem}
\usepackage{amsmath}
\usepackage{textcomp}
\usepackage{amssymb}
\usepackage{capt-of}
\usepackage{hyperref}
\usepackage[backend=bibtex,sorting=none, style=numeric-comp, citestyle=numeric-comp]{biblatex}
\usepackage{endnotes}
\bibliography{H2v01.bib} %% point at your bib file
\usepackage{tikz,bm}
\usepackage{epstopdf}
\graphicspath{{./Figures/}}
\definecolor{mcgillred}{RGB}{237, 27, 47}
\definecolor{darkred}{RGB}{158,9,24}
\definecolor{palegray}{RGB}{244,244,244}
\definecolor{grayt}{RGB}{180,180,180}
\definecolor{grayb}{RGB}{228,228,228}
\definecolor{black}{RGB}{0,0,0}
\setbeamercolor{palette primary}{bg=mcgillred,fg=white}
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\setbeamercolor{palette tertiary}{bg=mcgillred,fg=white}
\setbeamercolor{structure}{fg=mcgillred}
\setbeamercolor{title}{fg=mcgillred}
\setbeamercolor{frametitle}{fg=mcgillred}
\setbeamercolor{block body}{bg=palegray,fg=black}
\setbeamercolor{block title}{bg=mcgillred,fg=white}
\setbeamerfont{title}{size=\Large, series=\bfseries}
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\setbeamerfont{alerted text}{series=\bfseries}
\setbeamercolor{block title alerted}{bg=red,fg=black}
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\newcommand{\nox}{\(\mathrm{NO_{x}}\)}
\newlength\figH
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\setbeamertemplate{caption}{\raggedright\insertcaption\par}
\setbeamerfont{caption}{size=\tiny}
\setlength\abovecaptionskip{-5pt}
\renewcommand{\footnote}{\endnote}
\usepackage{animate}
\usetheme{Boadilla}
\author{Nils Koch}
\date{}
\title{Figure update}
\subtitle{}
\hypersetup{
pdfauthor={Nils Koch},
pdftitle={Figure update},
pdfkeywords={},
pdfsubject={},
pdfcreator={Emacs 27.2 (Org mode 9.4.4)},
pdflang={English}}
\begin{document}
\maketitle
\section{Introduction}
\label{sec:org79d6537}
\begin{frame}[label={sec:orgb1bc930}]{Intro to org to Beamer}
\begin{itemize}
\item This is not that visually appealling, but I haven't taken the time to set the colors and style to my liking in the Latex header
\item I have tried to include as many examples of things I find useful as possible
\begin{itemize}
\item sometimes this makes the slide not make much sense, but the example of how to do things is hopefully useful
\end{itemize}
\item The only slight pain with using org for both Beamer and normal Latex pdf is:
\begin{itemize}
\item you cannot have the pdf open in some pdf viewers and export to it (eg adobe)
\item I use Sumatra (\url{https://www.sumatrapdfreader.org/free-pdf-reader})
\begin{itemize}
\item can have your pdf open in sumatra, export to it and it will update the pdf to the new exported file while open
\end{itemize}
\end{itemize}
\end{itemize}
\end{frame}
\section{Figure update}
\label{sec:org5e0c8fa}
\begin{frame}[label={sec:org9c64cb6}]{Firing Characterization}
\vspace{-0.5cm}
\begin{columns}
\begin{column}[t]{0.65\columnwidth}
\begin{itemize}
\item Firing is a complicated phenomenon
\item How to best characterize it?
\begin{itemize}
\item rheobase
\item AUC
\end{itemize}
\end{itemize}
\end{column}
\begin{column}[t]{0.35\columnwidth}
\begin{center}
\includegraphics[width=0.95\textwidth]{firing_characterization.pdf}
\end{center}
\end{column}
\end{columns}
\end{frame}
\begin{frame}[label={sec:orgca6ec9d}]{Diversity in Firing Properties of the Models}
\begin{center}
\includegraphics[width=0.55\textwidth]{diversity_in_firing.pdf}
\end{center}
\end{frame}
\begin{frame}[label={sec:org47d8006}]{Sensitivy analysis: OFAT}
\vspace{-2cm}
\begin{itemize}
\item[{$\square$}] one factor at a time sensitivity analysis
\item simulate firing responses
\begin{itemize}
\item compute fI curves
\begin{itemize}
\item get rheobase
\item compute AUC
\end{itemize}
\end{itemize}
\end{itemize}
\end{frame}
\begin{frame}[label={sec:org7ee95f9}]{Rheobase sensitivity Analysis}
\begin{center}
\includegraphics[width=0.85\textwidth]{rheobase_correlation.pdf}
\end{center}
\tiny Koch et al. 2022
\end{frame}
\begin{frame}[label={sec:org43a0268}]{AUC Sensitivity Analysis}
\begin{itemize}
\item AUC = area under the curve
\end{itemize}
\begin{center}
\includegraphics[width=0.75\textwidth]{AUC_correlation.pdf}
\end{center}
\begin{itemize}
\item AUC over the initial non-zero fI curve is a proxy for slope
\end{itemize}
\end{frame}
\begin{frame}[label={sec:orgba8be96}]{\(K_V1.1\) Mutations}
\begin{center}
\includegraphics[width=0.95\textwidth]{simulation_model_comparison.pdf}
\end{center}
\end{frame}
\begin{frame}[label={sec:orgbe7a060}]{Ramp Firing}
\begin{center}
\includegraphics[width=0.95\textwidth]{ramp_firing.pdf}
\end{center}
\end{frame}
\end{document}