diff --git a/Figures/diversity_in_firing.py b/Figures/diversity_in_firing.py index 5c3c30b..f974fa5 100644 --- a/Figures/diversity_in_firing.py +++ b/Figures/diversity_in_firing.py @@ -100,7 +100,7 @@ def plot_spike_train(ax, model='RS Pyramidal', stop=750): ax.set_xlabel('Time [s]') ax.set_ylim(-85, 60) ax.axis('off') - ax.set_title(model, fontsize=7) + ax.set_title(model, fontsize=7, y=1.1) def plot_fI(ax, model='RS Pyramidal'): @@ -254,7 +254,7 @@ add_scalebar(ax12_spikes, matchx=False, matchy=False, hidex=True, hidey=True, si # add subplot labels for i in range(0,len(models)): # spike_axs[i].text(-0.18, 1.08, string.ascii_uppercase[i], transform=spike_axs[i].transAxes, size=10, weight='bold') - spike_axs[i].text(-0.572, 1.2, string.ascii_uppercase[i], transform=spike_axs[i].transAxes, size=10, weight='bold') + spike_axs[i].text(-0.572, 1.3, string.ascii_uppercase[i], transform=spike_axs[i].transAxes, size=10, weight='bold') # save fig.set_size_inches(cm2inch(21,15)) fig.savefig('./Figures/diversity_in_firing_diagram.jpg', dpi=300, bbox_inches='tight') #pdf # eps diff --git a/Figures/diversity_in_firing_diagram.jpg b/Figures/diversity_in_firing_diagram.jpg index e6557bb..14d0cec 100644 Binary files a/Figures/diversity_in_firing_diagram.jpg and b/Figures/diversity_in_firing_diagram.jpg differ diff --git a/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.pdf b/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.pdf index 1f138ec..1363179 100644 Binary files a/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.pdf and b/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.pdf differ diff --git a/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.tex b/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.tex index aa6c4eb..23180a9 100644 --- a/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.tex +++ b/Frontiers_manuscript/For_Submission/Koch_frontiers_diff.tex @@ -1,7 +1,7 @@ \documentclass[utf8]{FrontiersinHarvard} %DIF LATEXDIFF DIFFERENCE FILE %DIF DEL Koch_Frontiers.tex Mon Mar 27 10:08:50 2023 -%DIF ADD Koch_Frontiers_revised.tex Mon Apr 24 18:53:51 2023 +%DIF ADD Koch_Frontiers_revised.tex Tue Apr 25 10:43:03 2023 \DeclareUnicodeCharacter{03B2}{\(\beta\)} \DeclareUnicodeCharacter{03B1}{\(\alpha\)} \DeclareUnicodeCharacter{00C5}{\AA} @@ -113,6 +113,7 @@ $^{3}$Department of Neurology and Epileptology, Hertie Institute for Clinical Br \end{abstract} \DIFaddbegin +\setcounter{section}{0} \DIFaddend \section{Introduction} The properties and combinations of voltage-gated ion channels are vital in determining neuronal excitability \citep{bernard_channelopathies_2008, carbone_ion_2020, rutecki_neuronal_1992, pospischil_minimal_2008}. However, ion channel function can be disturbed, for instance through genetic alterations, resulting in altered neuronal firing behavior \citep{carbone_ion_2020}. In recent years, next generation sequencing has led to an increase in the discovery of clinically relevant ion channel mutations and has provided the basis for pathophysiological studies of genetic epilepsies, pain disorders, dyskinesias, intellectual disabilities, myotonias, and periodic paralyses \citep{bernard_channelopathies_2008, carbone_ion_2020}. Ongoing efforts of many research groups have contributed to the current understanding of underlying disease mechanism in channelopathies. However, a complex pathophysiological landscape has emerged for many channelopathies and is likely a reason for limited therapeutic success with standard care. diff --git a/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.pdf b/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.pdf index 65457e3..8b8c9b3 100644 Binary files a/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.pdf and b/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.pdf differ diff --git a/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.tex b/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.tex index b9ac04f..dee7f24 100644 --- a/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.tex +++ b/Frontiers_manuscript/For_Submission/Koch_frontiers_revised.tex @@ -66,6 +66,7 @@ $^{3}$Department of Neurology and Epileptology, Hertie Institute for Clinical Br \keyFont{ \section{Keywords:} Channelopathy, Epilepsy, Ataxia, Potassium Current, Neuronal Simulations, Conductance-based Models, Neuronal heterogeneity } \end{abstract} +\setcounter{section}{0} \section{Introduction} The properties and combinations of voltage-gated ion channels are vital in determining neuronal excitability \citep{bernard_channelopathies_2008, carbone_ion_2020, rutecki_neuronal_1992, pospischil_minimal_2008}. However, ion channel function can be disturbed, for instance through genetic alterations, resulting in altered neuronal firing behavior \citep{carbone_ion_2020}. In recent years, next generation sequencing has led to an increase in the discovery of clinically relevant ion channel mutations and has provided the basis for pathophysiological studies of genetic epilepsies, pain disorders, dyskinesias, intellectual disabilities, myotonias, and periodic paralyses \citep{bernard_channelopathies_2008, carbone_ion_2020}. Ongoing efforts of many research groups have contributed to the current understanding of underlying disease mechanism in channelopathies. However, a complex pathophysiological landscape has emerged for many channelopathies and is likely a reason for limited therapeutic success with standard care. @@ -80,7 +81,7 @@ In this study, we therefore investigated how the outcome of ionic current kineti \section{Material and Methods} All modelling and simulation was done in parallel with custom written Python 3.8 (Python Programming Language; RRID:SCR\_008394) software, run on a Cent-OS 7 server with an Intel(R) Xeon (R) E5-2630 v2 CPU. - + \subsection{Different Neuron Models} A set of single-compartment, conductance-based neuronal models representing the major classes of cortical and thalamic neurons including regular spiking pyramidal (RS pyramidal; model D), regular spiking inhibitory (RS inhibitory; model B), and fast spiking (FS; model C) neurons were used \citep{pospischil_minimal_2008}. Additionally, a \Kv current (\IKv; \citealt{ranjan_kinetic_2019}) was added to each of these models (RS pyramidal +\Kv; model H, RS inhibitory +\Kv; model E, and FS +\Kv; model G respectively). A cerebellar stellate cell model from \citet{alexander_cerebellar_2019} is used (Cb stellate; model A) in this study. This neuron model was also extended by a \Kv current \citep{ranjan_kinetic_2019}, either in addition to the A-type potassium current (Cb stellate +\Kv; model F) or by replacing the A-type potassium current (Cb stellate \(\Delta\)\Kv; model J). A subthalamic nucleus (STN; model L) neuron model as described by \citet{otsuka_conductance-based_2004} was also used. The STN neuron model (model L) was additionally extended by a \Kv current \citep{ranjan_kinetic_2019}, either in addition to the A-type potassium current (STN +\Kv; model I) or by replacing the A-type potassium current (STN \(\Delta\)\Kv; model K). Model letter naming corresponds to panel lettering in Figure \ref{fig:diversity_in_firing}. The anatomical origin of each model is shown in Figure \ref{fig:diversity_in_firing}~M. The properties and maximal conductances of each model are detailed in Table \ref{tab:g} and depicted in Figure \ref{fig:model_g}. The gating properties are unaltered from the original Cb stellate (model A) and STN (model L) models \citep{alexander_cerebellar_2019, otsuka_conductance-based_2004}. For enabling the comparison of models with the typically reported electrophysiological data fitting reported and for ease of further gating curve manipulations, a modified Boltzmann function \begin{equation}\label{eqn:Boltz} diff --git a/Frontiers_manuscript/For_Submission/diversity_in_firing_diagram.jpg b/Frontiers_manuscript/For_Submission/diversity_in_firing_diagram.jpg index e6557bb..14d0cec 100644 Binary files a/Frontiers_manuscript/For_Submission/diversity_in_firing_diagram.jpg and b/Frontiers_manuscript/For_Submission/diversity_in_firing_diagram.jpg differ