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@ -387,13 +387,13 @@ Diversity across neurons is not limited to gene expression and can also be seen
%Taken together, the nervous system consists of a vastly diverse and heterogenous collection of neurons with variable properties and characteristics including diverse combinations and expression levels of ion channels which are vital for neuronal firing dynamics. %Taken together, the nervous system consists of a vastly diverse and heterogenous collection of neurons with variable properties and characteristics including diverse combinations and expression levels of ion channels which are vital for neuronal firing dynamics.
\notels{with our models we tried to get this diversity and it's relevant} \notels{with our models we tried to get this diversity and it's relevant}
To capture the diversity in neuronal ion channel expression and its relevance in the outcome of ion channel mutations, multiple neuronal models with different ionic currents and underlying firing dynamics are \notels{were(?)} used here. To capture the diversity in neuronal ion channel expression and its relevance in the outcome of ion channel mutations, multiple neuronal models with different ionic currents and underlying firing dynamics were used here.
\subsection*{Ionic Current Environments Determine the Effect of Ion Channel Mutations} \subsection*{Ionic Current Environments Determine the Effect of Ion Channel Mutations}
To our knowledge, no comprehensive evaluation of how ionic current environment and cell type affect the outcome of ion channel mutations have been reported. But comparisons between the effects of such mutations between certain cell types were described. For instance, the R1628H mutation in SCN1A results in selective hyperexcitability of cortical pyramidal neurons, but causes hypoexcitability of adjacent inhibitory GABAergic neurons To our knowledge, no comprehensive evaluation of how ionic current environment and cell type affect the outcome of ion channel mutations have been reported. However, comparisons between the effects of such mutations between certain cell types were described. For instance, the R1628H mutation in SCN1A results in selective hyperexcitability of cortical pyramidal neurons, but causes hypoexcitability of adjacent inhibitory GABAergic neurons
% mutations in the SCN1A gene encoding \(\textrm{Na}_{\textrm{V}}\textrm{1.1}\) result in epileptic phenotypes by selective hypoexcitability of inhibitory but not excitatory neurons in the cortex resulting in circuit hyperexcitability % mutations in the SCN1A gene encoding \(\textrm{Na}_{\textrm{V}}\textrm{1.1}\) result in epileptic phenotypes by selective hypoexcitability of inhibitory but not excitatory neurons in the cortex resulting in circuit hyperexcitability
\citep{Hedrich14874}. In CA3 of the hippocampus, the equivalent mutation in SCN8A, R1648H, increases excitability of pyramidal neurons and decreases excitability of parvalbumin positive interneurons \citep{Hedrich14874}. In CA3 of the hippocampus, the equivalent mutation in SCN8A, R1648H, increases excitability of pyramidal neurons and decreases excitability of parvalbumin positive interneurons
% mutation of \(\textrm{Na}_{\textrm{V}}\textrm{1.6}\) similarly results in increased excitability of pyramidal neurons and decreased excitability of parvalbumin positive interneurons % mutation of \(\textrm{Na}_{\textrm{V}}\textrm{1.6}\) similarly results in increased excitability of pyramidal neurons and decreased excitability of parvalbumin positive interneurons