279 lines
11 KiB
TeX
279 lines
11 KiB
TeX
% Created 2022-02-16 Wed 15:42
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\date{}
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\title{Nils Koch}
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\hypersetup{
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pdfauthor={},
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pdftitle={Nils Koch},
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pdfkeywords={},
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pdfsubject={},
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pdfcreator={Emacs 27.2 (Org mode 9.4.4)},
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pdflang={English}}
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\begin{document}
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\renewcommand{\maketitle}
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\maketitle{
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\begin{center}
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\Huge \textbf{Update on Figures}}}\\
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}
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%\thispagestyle{empty} %remove header on first page
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\newcommand{\squishend}{\end{list} }
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\section*{Firing Characterization:}
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\label{sec:orgefc49e8}
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\subsection*{Question figure addresses:}
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\label{sec:org08ca3c5}
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Firing is a complicated phenomenon. How can it be simply characterized to compare the
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effects of changes in current properties?
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\subsection*{Method by which data is generated:}
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\label{sec:org68edbd3}
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Schematic diagram that does not contain underlying data - contains different square
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root functions.
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\subsection*{Conclusion from Figure:}
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\label{sec:org320d05e}
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Firing can be characterized by the rheobase and the AUC (proprotional to the increase in
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firing after the rheobase). The rheobase and firing in a small range above it (AUC) are
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likely important for determining network excitability (I think this makes sense,
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would need references to support this).
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\begin{figure}[H]
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\includegraphics[align=c,width=10cm]{firing_characterization.pdf}
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\caption{A. Demonstrates AUC in cyan. B. Demonstrates what combinations of increased and
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decreased rheobase and AUC look like in terms of fI curves.}
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\label{fig:firing_charact}
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\end{figure}
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\section*{Diversity in Model Firing:}
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\label{sec:org411197c}
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We have used a number of neuronal models that do not burst to look at the effects
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of changes in current properties in firing given different cell types/current
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environments
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\subsection*{Question figure addresses:}
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\label{sec:orge37c0bb}
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Which model is used?
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\subsection*{Rationale:}
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\label{sec:orga9c3a57}
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The effect of a change in a current property cannot be assessed in only one cell
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type to understand the general effects of this change and to assess whether differences
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occur across cell types.
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\subsection*{Method by which data is generated:}
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\label{sec:orga107703}
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Models from different sources are used and an example spike train is shown for each model
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along with a fI curve. The black dot on the fI curve indicates where the spike train is
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taken from and the green and red dots indicate the current at which the first and last
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spike occurs from an increasing and decreasing current ramp respectively. (These ramps
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can be seen in the ramp figure at the end).
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\subsection*{Conclusion from Figure:}
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\label{sec:org8a15a73}
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The models use are diverse and display a variety of spike shapes, firing behaviours, and
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fI curve shapes.
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\begin{figure}[H]
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\includegraphics[align=c,width=18cm]{diversity_in_firing.pdf}
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\caption{Spike trains and corresponding fI curves from: A. Cb stellate, B. RS Inhibitory,
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C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
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where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
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and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+ current for Kv1.1. The black
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dot on the fI curve indicates where the spike train is taken from and the green and red
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dots indicate the current at which the first and last spike occurs from an increasing and
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decreasing current ramp respectively.}
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\label{fig:div_firing}
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\end{figure}
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\section*{Rheobase Sensitivity Analysis:}
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\label{sec:org1e03320}
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I am not yet happy with this figure's layout
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\subsection*{Question figure addresses:}
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\label{sec:org696855b}
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How is rheobase affected by changes in current properties across models? Is the change
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in rheobase always in the same direction across models?
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\subsection*{Method by which data is generated:}
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\label{sec:org09129b8}
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A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
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to all or most models, where one current property was changed systematically at a time,
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the firing responses simulated and the fI curves computed. From this fI curve the
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largest injected current at which no firing occurs and the smallest injected
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current at which firing occurs were obtained. This current interval was then simulated
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to obtain the rheobase at greater resolution.
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\subsection*{Conclusion from Figure:}
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\label{sec:orga1ee38f}
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Generally the effect on rheobase is similar across all models/current environments
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\begin{figure}[H]
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\includegraphics[align=c,width=18cm]{rheobase_correlation.pdf}
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\caption{}
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\label{fig:rheo}
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\end{figure}
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\section*{AUC Sensitivity Analysis:}
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\label{sec:orgea61060}
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I prefer the first layout
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\subsection*{Question figure addresses:}
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\label{sec:org73643ea}
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How is AUC affected by changes in current properties across models? Is the change
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in AUC rheobase always in the same direction across models?
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\subsection*{Method by which data is generated:}
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\label{sec:org4e1eb8f}
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A one factor at a time (OFAT) sensitivity analysis was performed on the currents common
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to all or most models, where one current property was changed systematically at a time,
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the firing responses simulated and the steady-state fI curves computed. From this fI
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curve the largest injected current at which no firing occurs was obtained and the
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integral from this current using the composite trapezoidal rule for 1/5 of the current
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range.
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\subsection*{Conclusion from Figure:}
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\label{sec:org8eb1892}
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A given current property change does not necessarily cause the same
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change in rheobase and as such the outcome of a given change is dependent on the
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current environment or cell type.
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\begin{figure}[H]
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\includegraphics[align=c,width=18cm]{AUC_correlation.pdf}
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\caption{}
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\label{fig:AUC}
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\end{figure}
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\section*{Kv1.1 mutation simulation:}
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\label{sec:org095a1ae}
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\subsection*{Question figure addresses:}
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\label{sec:org12e9ebc}
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Do mutations of Kv1.1 cause similar effects on firing across cell types or is the effect
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cell type (and thus neuronal network) dependent?
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\subsection*{Method by which data is generated:}
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\label{sec:org094b162}
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Published Kv1.1 mutations (Lauxmann et al 2021) are simulated in all models containing
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Kv1.1 or an inactivating K\^{}+ current by altering the current properties according to
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those experimentally measured for each mutation. The firing of each model for each
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mutation are then simulated and the rheobase and AUC are computed.
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\subsection*{Conclusion from Figure:}
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\label{sec:orgd0738e2}
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The effects of Kv1.1 mutations on rheobase are highly correlated across models indicating
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that these mutations affect the rheobase in a similar fashion. However, the effect of
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Kv1.1 mutations vary across models as seen by the different correlation magnitudes
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between models. Thus although these mutations affect rheobase in a similar manner, the
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effect on AUC cannot easily be generalized and depends on cell type.
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Furthermore, this Figure demonstrates why characterization of mutations in terms of
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LOF or GOF in relation to firing overlooks potentially important characteristics of
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the changes in firing seen in different cell types. Thus, the characterization LOF
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and GOF is useful at a channel level to characterize the effects of a mutation on
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the current, but cannot and should not be blindly extended to characterize the
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effects of the mutation on firing as LOF and GOF, not only because the current
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environment in which this mutation occurs is a key determinant of the firing outcome,
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but also that firing is complex and not easily characterized as LOF or GOF.
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\begin{figure}[H]
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\includegraphics[align=c,width=18cm]{simulation_model_comparison.pdf}
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\caption{}
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\label{fig:kv11}
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\end{figure}
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\section*{Ramp Firing - For Supplements?:}
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\label{sec:orge8a0957}
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\subsection*{Question figure addresses:}
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\label{sec:org46e89c4}
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How does the firing of the models look like with a ramp protocol?
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\subsection*{Method by which data is generated:}
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\label{sec:org878a189}
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A 4 second ramp with the same current range as the step currents used to obtain fI
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plots is used and the firing of all models is simulated. The resulting spike trains
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are plotted.
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\subsection*{Conclusion from Figure:}
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\label{sec:org22fe40d}
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The diversity of firing seen with step currents is also seen with current ramps. The
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ramps highlight the hysteresis in models.
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\begin{figure}[H]
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\includegraphics[align=c,width=20cm]{ramp_firing.pdf}
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\caption{A. Cb stellate, B. RS Inhibitory,
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C. FS, D. RS Pyramidal, E. RS Inhibitory +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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F. Cb stellate +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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G. FS +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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H. RS Pyramidal +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), I. STN +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\),
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J.Cb stellate \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) , K. STN \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\), L. STN,
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where +\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the addition of Kv1.1 to the model
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and \(\Delta\)\(\mathrm{K}_{\mathrm{V}}\mathrm{1.1}\) indicates the exchange of the A type K+
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current for Kv1.1.}
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\label{fig:ramp}
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\end{figure}
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\end{document}
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