\documentclass[11pt]{article} \usepackage{amsfonts,amsbsy, amssymb, graphicx} % Tree-saver \setlength{\textwidth}{8.276in} \setlength{\textheight}{11.705in} %Allow 1in margin on each side and nothing else \addtolength{\textwidth}{-2in} \addtolength{\textheight}{-2in} \setlength{\oddsidemargin}{0pt} \setlength{\evensidemargin}{\oddsidemargin} \setlength{\topmargin}{0pt} \addtolength{\topmargin}{-\headheight} \addtolength{\topmargin}{-\headsep} \input mfpic.tex \renewcommand{\baselinestretch}{1.3} \renewcommand{\mathrm}[1]{{\mbox{\tiny #1}}} \newcommand{\dfrac}[2]{\displaystyle{\frac{#1}{#2}}} \newcommand{\ds}[1]{\displaystyle#1} \newcommand{\bs}[0]{\boldsymbol} \parindent=0pt \parskip=5pt \title{\LARGE\bf Increased computational accuracy in multi-compartmental cable models by a novel approach for precise point process localization} \author{\Large\bf A.E. Lindsay\\ Department of Mathematics, University of Edinburgh,\\ Edinburgh EH9 3JZ \\[10pt] \Large\bf K.A. Lindsay \\ Department of Mathematics, University of Glasgow,\\ Glasgow G12 8QQ \\[10pt] \Large\bf J.R. Rosenberg$^\dagger$\\ Division of Neuroscience and Biomedical Systems,\\ University of Glasgow, Glasgow G12 8QQ} \makeatletter \def\@cite#1#2{{#1\if@tempswa , #2\fi}} \def\@biblabel#1{ } %\def\@biblabel#1{#1.} \makeatother \begin{document} \opengraphsfile{mfpic} \maketitle \thispagestyle{empty} \vfil \begin{tabular}{ll} $^\dagger$ & \textbf{Corresponding author} \\[5pt] & J.R. Rosenberg \\ & West Medical Building \\ & Division of Neuroscience and Biomedical Systems \\ & University of Glasgow \\ & Glasgow G12 8QQ \\ & Scotland UK \\[5pt] & Tel\quad(+44) 141 330 6589 \\ & Fax\quad(+44) 141 330 2923 \\ & Email \verb$j.rosenberg@bio.gla.ac.uk$\\[10pt] & \textbf{Keywords} \\[5pt] & Compartmental models, Dendrites, Cable Equation \end{tabular} \vfil \pagebreak[4] \begin{center} \begin{tabular}{p{5.2in}} \multicolumn{1}{c}{\textbf{Abstract}}\\[10pt] Compartmental models of dendrites are the most widely used tool for investigating their electrical behaviour. Traditional models assign a single potential to a compartment. This potential is associated with the membrane potential at the centre of the segment represented by the compartment. All input to that segment, independent of its location on the segment, is assumed to act at the centre of the segment with the potential of the compartment. By contrast, the compartmental model introduced in this article assigns a potential to each end of a segment, and takes into account the location of input to a segment on the model solution by partitioning the effect of this input between the axial currents at the proximal and distal boundaries of segments. For a given neuron, the new and traditional approaches to compartmental modelling use the same number of locations at which the membrane potential is to be determined, and lead to ordinary differential equations that are structurally identical. However, the solution achieved by the new approach gives an order of magnitude better accuracy and precision than that achieved by the latter in the presence of point process input. \end{tabular} \end{center} \pagebreak[4] \input NC1.tex \input NC2.tex \input NC3.tex \input NC4.tex \input NC5.tex \input NC6.tex \closegraphsfile \end{document} Compartmental models have become important tools for investigating the behaviour of neurons to the extent that a number of packages exist to facilitate their implementation (\emph{e.g.} Hines and Carnevale \cite{Hines97}; Bower and Beeman \cite{Bower97}). Their use is motivated by the desire to reduce the mathematical complexity inherent in a continuum description of a neuron. This simplification is achieved by replacing the partial differential equations defining the continuum description of a neuron by a compartmental model of the neuron in which its behaviour is described by the solution of a set of ordinary differential equations (Rall, \cite{Rall64}). The traditional approach to compartmental modelling, introduced by Rall (\cite{Rall64}), assumes that a ``lump of membrane becomes a compartment; the rate constants governing exchange between compartments are proportional to the series conductance between them". Rall's definition of a compartmental model thus distinguishes between the input acting on a localised region of neuronal membrane (the compartment) and the resistive properties of the axoplasm which determines the conductances linking compartments in his model. Other authors (\emph{e.g.} Segev and Burke, \cite{Segev98}) treat the neuronal segment, including the membrane and axoplasm, as the compartment. Both definitions, however, associate a single potential with a compartment, and assume that all input falling on the segment that is represented by the compartment will act with this potential. For this reason these compartments are iso-potential, and indeed Segev and Burke (\cite{Segev98}) state this explicitly. Of course, iso-potential compartments are a feature of the model and \emph{should not be confused} with the true potential distribution within segments. Compartmental models in which a compartment has a single potential are aesthetically unsatisfactory since a compartment of this type cannot act as the fundamental unit in the construction of a model dendrite for two reasons. First, compartments defined by a single potential must coexist in pairs in order to support axial current flow, and second, half compartments are required to represent branch points and dendritic terminals (\emph{e.g.}, Segev and Burke, \cite{Segev98}). In the new approach to compartmental modelling presented in this article, two potentials are assigned to each compartment --- one to represent the membrane potential at the proximal boundary of the segment and the other to represent the membrane potential at its distal boundary. The new compartment can exist as an independent entity without the need to introduce half compartments, and can therefore function as the basic building block of a multi-compartmental neuronal model. The new compartments more accurately describe the influence of point current and synaptic input to the segments they represent than those of a traditional compartmental model. The accuracy of the new and traditional approaches to compartmental modelling is first assessed by calculating the error in the somal potential of a test neuron when each approach is used to calculate this potential ten milliseconds after the initiation of large scale point current input. In a second comparison, the accuracy of the two approaches is assessed by comparing the statistics of the spike train output generated by each type of compartmental model of the test neuron when subjected to large scale synaptic input.