\documentclass{slides} \usepackage{amsfonts,amsbsy,amssymb,graphicx} % Tree-saver %\setlength{\textwidth}{11.705in} %\setlength{\textheight}{8.276in} \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 \newcommand{\dfrac}[2]{\displaystyle{\frac{#1}{#2}}} \newcommand{\bs}[1]{\boldsymbol{#1}} \def\ds{\displaystyle} \def\ss{\,\scriptsize} \begin{document} \opengraphsfile{mfpic} % % \begin{slide} \begin{center} {\bf Some new ideas in compartmental modelling}\\[60pt] K.A. Lindsay, \\ Department of Mathematics, University of Glasgow\\[40pt] A.E. Lindsay, \\ Department of Mathematics, University of Edinburgh\\[40pt] J.R. Rosenberg \\ Division of Neuroscience and Biomedical Systems, University of Glasgow \end{center} \end{slide} % % \begin{slide} \begin{center} \textbf{Some general observations on \\ compartmental models} \end{center} \begin{enumerate} \item Motivation for compartmental modelling is the desire to reduce the mathematical complexity inherent in a continuum description of a neuron. \item A localised region of neuron (segment) and its input is described by an elementary unit (often a simple circuit) called a compartment. \item The model is constructed by joining compartments in a branching pattern corresponding to that of the neuron. \item Compartments can interact only with their nearest neighbours. \item Compartments are connected together by enforcing conservation of current. \end{enumerate} \end{slide} % % \begin{slide} \centerline{\textbf{Traditional compartmental models - I}} ``\dots \, each lump of membrane becomes a compartment; the rate constants governing exchange between compartments are proportional to the series conductance between them." \begin{flushright} Rall 1964 \end{flushright} \centerline{\begin{mfpic}[1][1]{0}{250}{-30}{50} \pen{1pt} \lines{(30,10),(70,10),(70,-10),(30,-10)} \dashed\lines{(30,10),(0,10)} \dashed\lines{(30,-10),(0,-10)} \rect{(80,10),(150,-10)} \lines{(200,10),(160,10),(160,-10),(200,-10)} \dashed\lines{(200,10),(230,10)} \dashed\lines{(200,-10),(230,-10)} \arrow\lines{(75,15),(75,5)} \arrow\lines{(75,-15),(75,-5)} \arrow\lines{(155,15),(155,5)} \arrow\lines{(155,-15),(155,-5)} \pen{2pt} \headlen7pt \lines{(40,15),(110,15)} \lines{(40,-15),(110,-15)} \lines{(120,15),(190,15)} \lines{(120,-15),(190,-15)} \tlabel[bc](75,20){\tiny \textsf{Membrane}} \tlabel[bc](155,20){\tiny \textsf{Membrane}} \end{mfpic}} ``Cable theory and compartmental models are \underline{complementary} approaches $\cdots$ cable theory regards dendrites as continuous cylindrical or conical structures, whereas a compartmental model approximates a continuous dendrite (or dendritic tree) as a set of resistively coupled iso-potential regions.'' \begin{flushright} Perkel and Mulloney 1978. \end{flushright} \vfill \end{slide} % % \begin{slide} \centerline{\textbf{Traditional compartmental models - II}} ``Spatial discretization of this partial differential equation (cable equation) is equivalent to reducing the spatially distributed neuron to a set of connected compartments.'' ``Spatially varying membrane current is represented by its value at the center of the compartment. This is much less drastic than the often heard statement that a compartment is assumed to be iso-potential.'' \begin{flushright} Hines and Carnevale 1997 \end{flushright} ``The compartmental approach \underline{replaces} the continuous differential equations of the analytical model by a set of ordinary differential equations. Thus, if the continuously distributed system is divided into sufficiently small segments (or compartments), one makes a negligibly small error by assuming that each compartment is iso-potential and spatially uniform in its properties.'' \begin{flushright} Segev and Burke 1998 \end{flushright} \vfill \end{slide} % % \begin{slide} \begin{center} \textbf{Summary of traditional models} \end{center} \begin{itemize} \item Two different definitions of a compartment. Despite these conceptual differences, both approaches lead to the same mathematical model. \item Each compartment has a single associated potential. \item Compartments cannot exist as independent entities, and therefore seem to be an inappropriate choice for the fundamental building blocks of a compartmental model. For example:- \begin{enumerate} \item Half-compartments may be needed to model the behaviour of terminals. \item The quantification of axial current requires two neighbouring compartments. \end{enumerate} \end{itemize} \end{slide} % % \begin{slide} \centerline{\textbf{How to define a compartment?}} \textbf{Some guidance} We form for ourselves images of symbols of external objects; and the form that we give to them is such that the necessary consequences of the images in thought are always images of the necessary consequences in nature of the things pictured. \begin{flushright} Hertz: \emph{Principles of Mechanics} \end{flushright} The function of the model is to represent the necessity that exists in nature by the logical necessity of the model. In the case of a good model one parallels the other. \begin{flushright} Regnier: \emph{Les Infortunes de la Raison} \end{flushright} \end{slide} % % \begin{slide} \vfill \begin{quotation} \noindent In our view the primary weakness in traditional compartmental models is that their compartments lack the sensitivity necessary to reflect the location of input within a segment. (We demonstrate this to be the case). \end{quotation} \begin{quotation} \noindent It is also aesthetically unsatisfactory that traditional compartments cannot exist as isolated entities by contrast with the object they represent. \end{quotation} \vfil \end{slide} % % \begin{slide} \centerline{\textbf{New compartmental model}} \textbf{Idea}:- Assign two potentials to a compartment -- one potential at each end of the length of dendrite (segment) represented by the compartment. \begin{itemize} \item Every dendritic section is a whole number of compartments. \item Neighbouring compartments share potentials at common boundaries. \item Compartments need not be iso-potential regions of dendrite. \item Model equations are constructed by enforcing conservation of current at segment boundaries. \end{itemize} \vfill \end{slide} % % \begin{slide} \centerline{\textbf{Partitioning of transmembrane current}} \textbf{Problem}:- The new model requires all transmembrane current acting on a segment to be divided between the axial currents at the proximal and distal boundaries of the segment. \centerline{\begin{mfpic}[1][1]{0}{400}{-60}{100} \pen{1pt} \headlen7pt \rect{(0,0),(400,50)} \arrow\lines{(5,25),(25,25)} \tlabel[cl](30,25){\tiny $I_\mathrm{PD}+I_\mathrm{P}$} \arrow\lines{(375,25),(395,25)} \tlabel[cr](370,25){\tiny $I_\mathrm{PD}+I_\mathrm{D}$} \arrow\lines{(240,50),(240,75)} \tlabel[bc](230,85){\tiny $I_\mathrm{S}$} \arrow\lines{(265,25),(245,25)} \arrow\lines{(220,25),(235,25)} \tlabel[tc](0,-10){$\lambda=0$} \tlabel[tc](240,-10){$\lambda$} \tlabel[tc](400,-10){$\lambda=1$} \dashed\lines{(0,-30),(0,-60)} \dashed\lines{(240,-30),(240,-60)} \dashed\lines{(400,-30),(400,-60)} \dotsize=1.5pt \dotspace=4pt \tlabel[cc](120,-45){$R_\mathrm{P}(\lambda)$} \dotted\arrow\lines{(160,-45),(235,-45)} \dotted\arrow\lines{(80,-45),(5,-45)} \tlabel[cc](320,-45){$R_\mathrm{D}(\lambda)$} \dotted\arrow\lines{(360,-45),(395,-45)} \dotted\arrow\lines{(280,-45),(245,-45)} \end{mfpic}} The partitioning in this instance is: \[ \begin{array}{ll} \mbox{Towards }\lambda=0 \qquad& \frac{R_\mathrm{D}(\lambda)\,I_\mathrm{S}} {R_\mathrm{P}(\lambda)+R_\mathrm{D}(\lambda)}\\[30pt] \mbox{Towards }\lambda=1 \qquad& \frac{R_\mathrm{P}(\lambda)\,I_\mathrm{S}} {R_\mathrm{P}(\lambda)+R_\mathrm{D}(\lambda)} \end{array} \] \vfill \end{slide} % % \begin{slide} \centerline{\textbf{Distributed transmembrane current}} Consider a cylindrical dendritic segment of radius $a$, of length $L$ filled with axoplasm of conductance $g_\mathrm{A}$ and with membrane of constant conductance $g_\mathrm{M}$. A potential difference $V$ applied between the ends of segment induces axial current flow \[ \pi a^2 g_\mathrm{A} V/L \] and total transmembrane current flow \[ 2\pi a L g_\mathrm{M}\,(V/2)\,. \] The ratio of these currents is \[ \frac{I_\mathrm{Transmembrane}}{I_\mathrm{Axial}} =\frac{L^2 g_\mathrm{M}} {a g_\mathrm{A}}=\frac{L^2}{a^2}\, \Bigg( \frac{a g_\mathrm{M}}{g_\mathrm{A}}\Bigg). \] Typically $a g_\mathrm{M}/g_\mathrm{A}$ is small, say $\approx 10^{-5}$, which suggests that the transmembrane current acting on a segment is small by comparison with axial current for ``short'' segments. \end{slide} % % \begin{slide} \begin{center} \textbf{Schematic illustration of a segment} \end{center} The Figure illustrates a dendritic segment of length $h$ (cm) where $\lambda\in[0,1]$ indicates the fractional distance of a point of the segment from its proximal end ($\lambda=0$). \centerline{\begin{mfpic}[2][2]{-40}{140}{180}{310} \headlen7pt \pen{0.5pt} \dotspace=4pt \dotsize=1pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % LH cylinder \parafcn[s]{-180,180,5}{(100-21*sind(t),240+28*cosd(t))} \lines{(0,288),(100,268)} \lines{(0,192),(100,212)} % % Partial cylinder on left \dotted\parafcn[s]{0,180,5}{(36*sind(t),240+48*cosd(t))} \parafcn[s]{0,180,5}{(-36*sind(t),240+48*cosd(t))} % % Annotation of LH cylinder \dashed\arrow\lines{(0,240),(100,240)} \tlabel[bl](50,250){\large $I_\mathrm{PD}$} \tlabel[bc](0,250){$V_\mathrm{P}$} \tlabel[cc](0,180){\large $\lambda=0$} \tlabel[bc](0,295){\textsf{P}} \arrow\lines{(0,235),(0,200)} \tlabel[cr](-5,220){\textsf{$r_\mathrm{P}$}} % % Annotation of RH cylinder \tlabel[bc](100,250){$V_\mathrm{D}$} \tlabel[cc](100,180){\large $\lambda=1$} \tlabel[cc](100,280){\textsf{D}} \arrow\lines{(100,235),(100,216)} \tlabel[cl](105,228){\textsf{$r_\mathrm{D}$}} \arrow\lines{(60,228),(95,228)} \arrow\lines{(40,228),(5,228)} \tlabel[cc](50,228){$h$} \end{mfpic}} $I_\mathrm{PD}$ is axial current in the absence of transmembrane current. \end{slide} % % \begin{slide} \centerline{\textbf{Transmembrane current free solution}} \begin{itemize} \item Segment membrane is modelled by the frustum of a cone of radius \[ r(\lambda)=(1-\lambda)r_\mathrm{P}+\lambda r_\mathrm{D} \,,\qquad \lambda\in[0,1] \] formed by rotating the straight line PD about the axis of the dendrite \item Assuming axoplasm of constant axial conductance $g_\mathrm{A}$ and that no transmembrane current acts on the segment then \[ I_\mathrm{PD}= \frac{\pi g_\mathrm{A} r_\mathrm{P} r_\mathrm{D}}{h}\,\big(\,V_\mathrm{P}-V_\mathrm{D}\,\big) \] and the membrane potential at point $\lambda$ is \[ V(\lambda) = \frac{V_\mathrm{P}\,(1-\lambda)\, r_\mathrm{P}+V_\mathrm{D}\,\lambda\,r_\mathrm{D}} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\,. \] \end{itemize} \end{slide} % % \begin{slide} \centerline{\textbf{Transmembrane current}} Transmembrane current is usually described by the sum of four distinct components:- \begin{itemize} \item Capacitative current \[ \int 2\pi r(x) \,c_\mathrm{M}\,\frac{\partial V}{\partial t}\,dx \] \item Intrinsic voltage-dependent current (IVDC) \[ \int 2\pi r(x)\,J_\mathrm{IVDC}(V)\,dx \] \item Synaptic current \[ \sum J_\mathrm{SYN}(V_\mathrm{syn}) \] \item Exogenous current \[ \sum I_\mathrm{EX}(x,t) \] \end{itemize} The integrals and summations in these expressions are calculated over the segment. \end{slide} % % \begin{slide} \centerline{\textbf{Conservation of current}} Assume current $I_\mathrm{PD}+I_\mathrm{P}$ leaves the proximal boundary of a segment towards its distal boundary and that current $I_\mathrm{PD}+I_\mathrm{D}$ arrives at that distal boundary, then \[ I_\mathrm{P}-I_\mathrm{D}=h\int_0^1 J(\lambda,t)\,d\lambda\,. \] where \[ \begin{array}{rcl} h J(\lambda,t) & = & \ds 2\pi h r(\lambda)\,c_\mathrm{M}(\lambda)\, \frac{\partial V(\lambda,t)}{\partial t}\\[15pt] &&\quad\ds+\;2\pi h r(\lambda)\,J_\mathrm{IVDC}(V(\lambda,t))\\[10pt] &&\qquad \ds+\; \sum_k J_\mathrm{SYN}(V_\mathrm{syn})\, \delta(\lambda-\lambda_k)\\[10pt] &&\qquad\quad\ds+\;\sum_k I_\mathrm{EX}(t)\, \delta(\lambda-\lambda_k) \end{array} \] where $\lambda_k$ denotes the relative location of the $k^{th}$ synapse or exogenous input with respect to the proximal boundary of the segment. \end{slide} % % \begin{slide} \begin{center} \textbf{Partitioning rule for \\ transmembrane current} \end{center} \textbf{Task}: We need expressions for $I_\mathrm{P}$ and $I_\mathrm{D}$ that conserve current independently of the constitutive forms for $J(\lambda,t)$. \textbf{Idea}: Divide transmembrane current acting at point $\lambda$ between the proximal and distal boundaries of a segment in inverse proportion to the resistance of the segment lying between the point $\lambda$ and that boundary. This idea leads to the partitioning rule \[ \begin{array}{rcl} I_\mathrm{P} & = & \ds h\int_0^1 \frac{(1-\lambda)\,r_\mathrm{P}\, J(\lambda,t)\,d\lambda}{(1-\lambda)\,r_\mathrm{P} +\lambda\,r_\mathrm{D}}\,,\\[25pt] -I_\mathrm{D} & = & \ds h\int_0^1 \frac{\lambda\,r_\mathrm{D}\,J(\lambda,t)\,d\lambda} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\,. \end{array} \] The rule is based on the observation that \[ R_\mathrm{P}(\lambda) = \frac{\lambda h} {\pi g_\mathrm{A} r_\mathrm{P} r(\lambda)}\,,\quad R_\mathrm{D}(\lambda) = \frac{(1-\lambda)h} {\pi g_\mathrm{A} r_\mathrm{D} r(\lambda)}\,, \] and that \[ R_\mathrm{P}(\lambda)+R_\mathrm{D}(\lambda) = \frac{h} {\pi g_\mathrm{A} r_\mathrm{P} r_\mathrm{D}}\,. \] \end{slide} % % \begin{slide} \begin{center} \textbf{I - Exogenous point currents} \end{center} Let $\lambda_1,\cdots,\lambda_n$ be the locations of exogenous current input $\mathcal{I}_1,\ \cdots\ \mathcal{I}_n$ to a segment. The resulting transmembrane current is \[ \sum_{k=1}^n \mathcal{I}_k(t)\,\delta(\lambda-\lambda_k)\,. \] The perturbations $I_\mathrm{P}$ and $I_\mathrm{D}$ to $I_\mathrm{PD}$ are \[ \begin{array}{rcl} I_\mathrm{P} & = &\ds \sum_{k=1}^n\, \frac{r_\mathrm{P}}{r_k}\,(1-\lambda_k)\,\mathcal{I}_k(t)\,,\\[25pt] -I_\mathrm{D} & = &\ds \sum_{k=1}^n\, \frac{r_\mathrm{D}}{r_k}\,\lambda_k\,\mathcal{I}_k(t)\,, \end{array} \] where $r_k=(1-\lambda_k)\,r_\mathrm{P} +\lambda_k\,r_\mathrm{D}$. \end{slide} % % \begin{slide} \begin{center} \textbf{II - Synaptic point currents} \end{center} The current flow induced by $n$ synapses at points $\lambda_1,\lambda_2, \cdots, \lambda_n$ on a segment of length $h$ is represented by the Figure \centerline{\qquad\begin{mfpic}[1.3][1]{0}{300}{-30}{60} \pen{1pt} \headlen7pt % % Sealed cable \arrow\lines{(0,20),(25,20)} \arrow\lines{(40,20),(65,20)} \arrow\lines{(120,20),(145,20)} \arrow\lines{(160,20),(185,20)} \arrow\lines{(240,20),(265,20)} \arrow\lines{(280,20),(305,20)} % % \dotspace=4pt \dotsize=2pt \dotted\lines{(75,20),(110,20)} \dotted\lines{(195,20),(230,20)} % % Nodes on sealed cable \tlabel[cc](0,20){$\bullet$} \tlabel[cc](40,20){$\bullet$} \tlabel[cc](120,20){$\bullet$} \tlabel[cc](160,20){$\bullet$} \tlabel[cc](240,20){$\bullet$} \tlabel[cc](280,20){$\bullet$} \tlabel[cc](320,20){$\bullet$} % % Points on sealed cable \tlabel[bc](40,30){\tiny $\lambda_1$} \tlabel[bc](120,30){\tiny $\lambda_{k-1}$} \tlabel[bc](160,30){\tiny $\lambda_k$} \tlabel[bc](240,30){\tiny $\lambda_{n-1}$} \tlabel[bc](280,30){\tiny $\lambda_n$} % \tlabel[cc](20,10){\tiny $I_1$} \tlabel[cc](60,10){\tiny $I_2$} \tlabel[cc](140,10){\tiny $I_k$} \tlabel[cc](180,10){\tiny $I_{k+1}$} \tlabel[cc](260,10){\tiny $I_n$} \tlabel[cc](300,10){\tiny $I_{n+1}$} % % Sealed cable \arrow\lines{(40,10),(40,-10)} \tlabel[tc](40,-15){\tiny\textsf{$\mathcal{I}_1$}} \arrow\lines{(120,10),(120,-10)} \tlabel[tc](120,-15){\tiny\textsf{$\mathcal{I}_{k-1}$}} \arrow\lines{(160,10),(160,-10)} \tlabel[tc](160,-15){\tiny\textsf{$\mathcal{I}_k$}} \arrow\lines{(240,10),(240,-10)} \tlabel[tc](240,-15){\tiny\textsf{$\mathcal{I}_{n-1}$}} \arrow\lines{(280,10),(280,-10)} \tlabel[tc](280,-15){\tiny\textsf{$\mathcal{I}_n$}} \end{mfpic}} Synaptic input at $\lambda_k$ is modelled by the constitutive law \[ \mathcal{I}_k(t)=g_k(t)(V(\lambda_k,t)-E_k) \] where $E_k$ is the synaptic reversal potential and $g_k(t)$ is the time course of the synaptic conductance. The partitioning rule now gives \[ \begin{array}{rcl} I_\mathrm{P} & = &\ds \sum_{k=1}^n\, \frac{r_\mathrm{P}}{r_k}\,(1-\lambda_k)\,g_k(t)\Bigg[ V(\lambda_k,t)-E_k\Bigg]\,,\\[25pt] -I_\mathrm{D} & = &\ds \sum_{k=1}^n\, \frac{r_\mathrm{D}}{r_k}\,\lambda_k\,g_k(t)\Bigg[V(\lambda_k,t)-E_k\Bigg]\,, \end{array} \] but now $V(\lambda_k,t)$ is unknown. \vfill \end{slide} % % \begin{slide} \begin{center} \textbf{Preliminary idea} \end{center} \begin{itemize} \item Estimate $V(\lambda_k,t)$ by the formula \[ \widehat{V}_k(t)=V_\mathrm{P}(t)\,(1-\lambda_k)\, \frac{r_\mathrm{P}}{r_k}+V_\mathrm{D}(t)\,\lambda_k\, \frac{r_\mathrm{D}}{r_k}\,. \] \item For a single synapse at $\lambda_1$, the partitioning rule with $V(\lambda_k,t)=\widehat{V}_k(t)$ gives \[ \begin{array}{rcl} I_\mathrm{P} & = &\ds \frac{r_\mathrm{P}}{r_1}\,(1-\lambda_1)\,g_1(t) \Bigg[\widehat{V}_1(t)-E_1\Bigg]\,,\\[25pt] -I_\mathrm{D} & = & \ds\frac{r_\mathrm{D}}{r_1}\,\lambda_1\,g_1(t) \Bigg[\widehat{V}_1(t)-E_1\Bigg]\,. \end{array} \] \item In fact, the case of a single synaptic input at $\lambda_1$ has exact solution \[ \begin{array}{rcl} I_\mathrm{P} & = & \ds\frac{r_\mathrm{P}}{r_1}\, \frac{(1-\lambda_1)\,g_1(t)\Bigg[\widehat{V}_1(t)-E_1\Bigg]} {1+\frac{\lambda_1(1-\lambda_1 )h g_1}{\pi g_\mathrm{A} r^2_1}}\,,\\[35pt] -I_\mathrm{D} & = &\ds\frac{r_\mathrm{D}}{r_1}\, \frac{\lambda_1\,g_1(t)\Bigg[\widehat{V}_1(t)-E_1\Bigg]} {1+\frac{\lambda_1(1-\lambda_1 )h g_1}{\pi g_\mathrm{A} r^2_1}}\,. \end{array} \] The estimate $V(\lambda_k,t)=\widehat{V}_k(t)$ therefore overstates the influence of the synapse. \end{itemize} \end{slide} % % \begin{slide} \begin{center} \textbf{A more detailed analysis} \end{center} \textbf{Current conservation} at each synapse gives \[ I_{k+1}+g_k(V_k-E_k) = I_k\,,\quad k=1,\cdots,n \] where $V_k$ is the potential at $\lambda_k$ and \[ I_k = \frac{\pi g_\mathrm{A}r_{k-1}r_k} {h(\lambda_k-\lambda_{k-1})}\,\big(V_{k-1}-V_k\,\big) \] for $k=1,\cdots,(n+1)$. \vfil \textbf{Solve the equation} relating $I_k$ to $V_k$ to get \[ V_k = V_\mathrm{P} -\frac{h}{\pi g_\mathrm{A}}\,\sum_{j=1}^k \, \frac{(\lambda_j-\lambda_{j-1})I_j}{r_{j-1}r_j} \] for $k=1,\cdots,(n+1)$. The case $k=n+1$ is the constraint \[ \sum_{j=1}^{n+1} \, \frac{(\lambda_j-\lambda_{j-1})I_j}{r_{j-1}r_j}= \frac{h(V_\mathrm{P}-V_\mathrm{D})}{\pi g_\mathrm{A}}. \] \end{slide} % % \begin{slide} \textbf{Eliminate} $V_k$ from the current conservation condition to obtain $n$ linear equations connecting $I_1$ to $I_{n+1}$. The $(n+1)^{th}$ equation is the constraint. \textbf{Re-express} the equations for $I_1$ to $I_{n+1}$ in terms of $\widehat{I}_k=I_k-I_\mathrm{PD}$ where $\widehat{I}_k$ is the perturbation in $I_k$ from $I_\mathrm{PD}$. The equations satisfied by $\widehat{I}_0,\ \cdots \,\widehat{I}_{n+1}$ are {\tiny \[ \hskip-30pt\begin{array}{rcl} \ds\Big[1+\frac{\lambda_1 h g_1}{\pi g_\mathrm{A} r_\mathrm{P} r_1}\Big]\widehat{I}_1-\widehat{I}_2 & = & \mathcal{I}_1(t) \\[10pt] \vdots & &\vdots\\ \ds\frac{g_k h}{\pi g_\mathrm{A}}\sum_{j=1}^{k-1} \frac{(\lambda_j-\lambda_{j-1})\widehat{I}_j}{r_{j-1}r_j}+ \Big[1+\frac{(\lambda_k-\lambda_{k-1})hg_k}{\pi g_\mathrm{A} r_{k-1}r_k}\Big]\widehat{I}_k-\widehat{I}_{k+1} & = & \mathcal{I}_k(t)\\[10pt] \vdots & &\vdots\\ \ds\frac{g_n h}{\pi g_\mathrm{A}}\sum_{j=1}^{n-1} \frac{(\lambda_j-\lambda_{j-1})\widehat{I}_j}{r_{j-1}r_j}+ \Big[1+\frac{(\lambda_n-\lambda_{n-1})hg_n}{\pi g_\mathrm{A} r_{n-1}r_n}\Big]\widehat{I}_n-\widehat{I}_{n+1} & = & \mathcal{I}_n(t)\\[10pt] \ds\sum_{j=1}^{n+1}\frac{(\lambda_j-\lambda_{j-1}) \widehat{I}_j}{r_{j-1}r_j} & = & 0 \end{array} \] } where $\mathcal{I}_k(t)=g_k(t)\,[\,\widehat{V}_k-E_k\,]$. \end{slide} % % \begin{slide} These equations have matrix formulation \[ A\,\widehat{I}+GD\,\widehat{I}=\mathcal{I} \] where $G$ and $D$ are $(n+1)\times(n+1)$ matrices and \[ \begin{array}{rcl} \widehat{I} & = & [\widehat{I}_1,\ \cdots\ , \widehat{I}_{n+1}]^\mathrm{T}\\[10pt] \mathcal{I} & = & [\mathcal{I}_1,\ \cdots\ , \mathcal{I}_n,0\,]^\mathrm{T} \end{array} \] The matrix $A$ is { \tiny \[ \left[\begin{array}{ccccc} 1 & \hskip-9pt-1 & 0 & \cdots & 0 \\[5pt] 0 & 1 & \hskip-9pt-1 & \cdots & 0 \\[5pt] 0 & 0 & 1 & \cdots & 0 \\[5pt] \cdots & \cdots & \cdots & \cdots & \cdots \\[5pt] 0 & 0 & 0 & \cdots & \hskip-9pt-1 \\[5pt] \ds\frac{(\lambda_1-\lambda_0)}{r_0 r_1} & \ds\frac{(\lambda_2-\lambda_1)}{r_1 r_2} & \ds\frac{(\lambda_3-\lambda_2)}{r_2 r_3} & \cdots & \ds\frac{(\lambda_{n+1}-\lambda_n)}{r_n r_{n+1}} \end{array}\right] \] } with inverse {\tiny \[ \left[\begin{array}{ccccccc} (1-\lambda_1)\ds\frac{r_\mathrm{P}}{r_1} & (1-\lambda_2)\ds\frac{r_\mathrm{P}}{r_2} & (1-\lambda_3)\ds\frac{r_\mathrm{P}}{r_3} & \cdots & \cdots & r_\mathrm{P}r_\mathrm{D} \\[15pt] -\lambda_1\ds\frac{r_\mathrm{D}}{r_1} & (1-\lambda_2)\ds\frac{r_\mathrm{P}}{r_2} & (1-\lambda_3)\ds\frac{r_\mathrm{P}}{r_3} & \cdots & \cdots & r_\mathrm{P}r_\mathrm{D} \\[15pt] -\lambda_1\ds\frac{r_\mathrm{D}}{r_1} & -\lambda_2\ds\frac{r_\mathrm{D}}{r_2} & (1-\lambda_3)\ds\frac{r_\mathrm{P}}{r_3} & \cdots & \cdots & r_\mathrm{P}r_\mathrm{D} \\[15pt] \cdots & \cdots & \cdots & \cdots & \cdots & \cdots \\[15pt] -\lambda_1\ds\frac{r_\mathrm{D}}{r_1} & -\lambda_2\ds\frac{r_\mathrm{D}}{r_2} & -\lambda_3\ds\frac{r_\mathrm{D}}{r_3} & \cdots & (1-\lambda_n)\ds\frac{r_\mathrm{P}}{r_n} & r_\mathrm{P}r_\mathrm{D} \\[15pt] -\lambda_1\ds\frac{r_\mathrm{D}}{r_1} & -\lambda_2\ds\frac{r_\mathrm{D}}{r_2} & -\lambda_3\ds\frac{r_\mathrm{D}}{r_3} & \cdots & -\lambda_n\ds\frac{r_\mathrm{D}}{r_n} & r_\mathrm{P}r_\mathrm{D} \end{array}\right]\,. \] } \end{slide} % % \begin{slide} \textbf{Exogenous point current}: Here $G=0$ and therefore $\widehat{I}=A^{-1}\mathcal{I}$. In fact, only the first ($I_\mathrm{P}$) and last ($I_\mathrm{D}$) rows of $A^{-1}\mathcal{I}$ are needed. \textbf{General synaptic point current}: The first and last rows of $A^{-1}\mathcal{I}$ now give the preliminary estimates of $I_\mathrm{P}$ and $I_\mathrm{D}$ (which overestimate synaptic influence). Solve by rewriting $A\,\widehat{I}+GD\,\widehat{I}=\mathcal{I}$ as \[ A\,\widehat{I}^{\;(m+1)}=\mathcal{I}-GD\,\widehat{I}^{\;(m)} \] and iterate starting with $\widehat{I}^{\;(1)}=A^{-1}\mathcal{I}$. Clearly the solution for $\widehat{I}$ has generic form \[ \widehat{I} = \phi_1(t)V_\mathrm{P} + \phi_2(t)V_\mathrm{D}+\phi_3(t) \] where $\phi_1(t)$, $\phi_2(t)$ and $\phi_3(t)$ are functions of time only. \end{slide} % % \begin{slide} \begin{center} \textbf{III - Capacitative current} \end{center} The contribution of capacitative current is estimated by approximating the true membrane potential with $\widehat{V}(\lambda,t)$ to obtain \[ \begin{array}{rcl} I^\mathrm{\,cap}_\mathrm{P} & = & 2\pi\, r_\mathrm{P} h \ds\Bigg[r_\mathrm{P}\frac{dV_\mathrm{P}}{dt} \int_0^1\frac{(1-\lambda)^2 c_\mathrm{M}(\lambda)\,d\lambda} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\\[25pt] &&\ds\quad+r_\mathrm{D}\frac{dV_\mathrm{D}}{dt} \int_0^1 \frac{\lambda(1-\lambda)c_\mathrm{M}(\lambda)\,d\lambda} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\Bigg],\\[25pt] -I^\mathrm{\,cap}_\mathrm{D} & = & 2\pi\, r_\mathrm{D} h \ds\Bigg[r_\mathrm{P}\frac{dV_\mathrm{P}}{dt}\int_0^1\, \frac{\lambda(1-\lambda)c_\mathrm{M}(\lambda)\,d\lambda} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\\[25pt] &&\quad\ds+r_\mathrm{D}\frac{dV_\mathrm{D}}{dt}\int_0^1\,\frac{\lambda^2 c_\mathrm{M}(\lambda)\,d\lambda} {(1-\lambda)\,r_\mathrm{P}+\lambda\,r_\mathrm{D}}\,\Bigg]\,. \end{array} \] For a compartment with constant specific membrane capacitance in the shape of a uniform right circular cylinder, \[ \begin{array}{rcl} I^\mathrm{\,cap}_\mathrm{P} & = & \ds\frac{C}{6}\, \Bigg[\,2\frac{dV_\mathrm{P}}{dt}+\frac{dV_\mathrm{D}}{dt}\,\Bigg]\\[25pt] -I^\mathrm{\,cap}_\mathrm{D} & = & \ds\frac{C}{6}\, \Bigg[\,\frac{dV_\mathrm{P}}{dt}+2\frac{dV_\mathrm{D}}{dt} \,\Bigg] \end{array} \] where $C$ is the total membrane capacitance of the segment. \end{slide} % % \begin{slide} \begin{center} \textbf{IV - Intrinsic voltage-dependent current} \end{center} IVDC is often described by the constitutive law $J=g_\alpha(V)(V-E_\alpha)$ where $V$ is the membrane potential, $E_\alpha$ is the reversal potential for species $\alpha$ and $g_\alpha(V)$ is a voltage-dependent membrane conductance. For a compartment with constant specific membrane capacitance in the shape of a uniform right circular cylinder, \[ \begin{array}{rcl} I^\mathrm{\,ivdc}_\mathrm{P} & = & \ds\frac{\pi h r_\mathrm{P}}{6} \,\Bigg[\,(3g_\mathrm{P}+g_\mathrm{D})(V_\mathrm{P}-E)\\[10pt] &&\ds\qquad+\;(g_\mathrm{P}+g_\mathrm{D})(V_\mathrm{D}-E)\Bigg]\,,\\[20pt] -I^\mathrm{\,ivdc}_\mathrm{D} & = & \ds\frac{\pi h r_\mathrm{D}}{6} \,\Bigg[\,(g_\mathrm{P}+g_\mathrm{D})(V_\mathrm{P}-E)\\[10pt] &&\qquad+\;(g_\mathrm{P}+3g_\mathrm{D})(V_\mathrm{D}-E)\Bigg]. \end{array} \] where $g_\mathrm{P}=g_\alpha(V_\mathrm{P})$ and $g_\mathrm{D}=g_\alpha( V_\mathrm{D})$. \end{slide} % % \begin{slide} \begin{center} \textbf{Construction of the model equations} \end{center} The model (differential) equations are constructed as follows:- \textbf{Equate} the expression for the axial current at the distal boundary of one segment to that of the axial current at the proximal boundary of the neighbouring segment. \textbf{Apply} appropriate boundary conditions on the axial current at the distal boundary of each terminal segment (\emph{e.g.} current is zero). \textbf{Assert} that the sum of the axial currents at the proximal boundary of segments meeting at a branch point balances the axial current at the distal boundary of the parent segment. \textbf{Apply} a suitable somal boundary condition. \end{slide} % % \begin{slide} The model differential equations are integrated using the trapezoidal and midpoint quadratures, as appropriate. The reorganised equations can usually be expressed in the form \[ \begin{array}{ll} \ds A_\mathrm{L}(t_{k+1},t_k)\,V^{(k+1)} = & A_\mathrm{R}(t_{k+1},t_k)\,V^{(k)}\\[10pt] &\quad+B(t_{k+1},t_k)+O(h^3). \end{array} \] where $A_\mathrm{L}$ and $A_\mathrm{R}$ are sparse matrix with structural form that of the connectivity matrix of the neuron. \end{slide} % % \begin{slide} \begin{center} \textbf{Model Neuron} \end{center} The accuracy of the new and traditional compartmental models is compared using a branched neuron for which the continuum model has a closed form expression for the membrane potential in response to input. \[ \begin{array}{c} $\begin{mfpic}[1.3][1.3]{0}{220}{-20}{220} \pen{2pt} \dotsize=1pt \dotspace=3pt \lines{(-5,100),(5,110),(15,100),(5,90),(-5 ,100)} % Upper dendrite % Root branch \dotted\lines{(5,115),(15,170),(20,170)} \lines{(20.0,160),(36.7,160)} \tlabel[tc](28.4,150){\textsf{(a)}} % Level 1 \lines{(50.0,190),(88.3,190)} \tlabel[bc](75,200){\textsf{(c)}} \lines{(50.0,130),(91.0,130)} \tlabel[tc](75,120){\textsf{(d)}} \dotted\lines{(36.7,160),(45,200),(55,200)} \dotted\lines{(36.7,160),(45,120),(55,120)} % Level 2 \lines{(100.0,210),(153.2,210)} \lines{(100.0,190),(153.2,190)} \lines{(100.0,170),(153.2,170)} \tlabel[cl](160,210){\textsf{(g)}} \tlabel[cl](160,190){\textsf{(g)}} \tlabel[cl](160,170){\textsf{(g)}} \dotted\lines{(88.3,190),(95,220),(105,220)} \dotted\lines{(88.3,190),(95,160),(105,160)} \lines{(100.0,140),(165.1,140)} \lines{(100.0,120),(165.1,120)} \dotted\lines{(91.0,130),(95,150),(105,150)} \dotted\lines{(91.0,130),(95,110),(105,110)} \tlabel[cl](175,140){\textsf{(h)}} \tlabel[cl](175,120){\textsf{(h)}} % % Lower dendrite % Root branch \lines{(20.0,40),(58.0,40)} \dotted\lines{(5,85),(15,30),(25,30)} \tlabel[bc](39,50){\textsf{(b)}} % Level 1 \lines{(70.0,70),(133.1,70)} \lines{(70.0,10),(127.1,10)} \dotted\lines{(58,40),(66.5,80),(76.5,80)} \dotted\lines{(58,40),(66.5,0),(76.5,0)} \tlabel[bc](105,80){\textsf{(e)}} \tlabel[tc](105,0){\textsf{(f)}} % Level 2 \lines{(145,80),(195.1,80)} \lines{(145,60),(195.1,60)} \dotted\lines{(133.1,70),(140,90),(150,90)} \dotted\lines{(133.1,70),(140,50),(150,50)} \tlabel[cl](205,80){\textsf{(i)}} \tlabel[cl](205,60){\textsf{(i)}} \lines{(140,30),(179.6,30)} \lines{(140,10),(179.6,10)} \lines{(140,-10),(179.6,-10)} \dotted\lines{(127.1,10),(134,40),(144,40)} \dotted\lines{(127.1,10),(134,-20),(144,-20)} \tlabel[cl](190,30){\textsf{(j)}} \tlabel[cl](190,10){\textsf{(j)}} \tlabel[cl](190,-10){\textsf{(j)}} \end{mfpic}$ \end{array} \] The diameters and lengths of the dendritic sections are organised so that $l/\sqrt{r}$ is fixed for all children of each branch point. \end{slide} % % \begin{slide} It can be proved that the solution of any well-configured compartmental model of a neuron converges to the solution of the continuum model of that neuron in the limit as the maximum segment size tends to zero. The accuracy of the new compartmental model will be compared with that of a traditional compartmental model by measuring the closeness with which the solutions of both models estimate the exact solution for the somal potential of the continuum model. \end{slide} % % \begin{slide} \centerline{\textbf{Simulation exercises}} \begin{itemize} \item 75 exogenous point inputs each of strength $2\times10^{-5}\,\mu$A were distributed randomly over the branched model neuron. \item The difference between the exact somal potential and its value computed by each compartmental model was determined at one millisecond intervals for the first 10 milliseconds of the simulation. \item Each difference was divided by the (known) exact potential of the soma at that time to get relative errors for that model. \item For a fixed number of compartments, each simulation exercise consisted of 2000 repetitions of the procedure for each model (for identical input). \end{itemize} \end{slide} % % \begin{slide} \begin{center} \textbf{Results} \end{center} \vfil \centerline{\begin{mfpic}[84][36]{0.4}{3}{-7.2}{1.3} \headlen7pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % x-axis \tlabel[br](3.0,0.7){\tiny\textsf{$\log_{10}(\mbox{No. Compartments})$}} \lines{(1.0,0),(3.0,0)} \lines{(1.5,0),(1.5,-0.2)} \lines{(2.0,0),(2.0,-0.2)} \lines{(2.5,0),(2.5,-0.2)} \lines{(3.0,0),(3.0,-0.2)} \tlabel[bc](1.0,0.3){\tiny\textsf{1.0}} \tlabel[bc](1.5,0.3){\tiny\textsf{1.5}} \tlabel[bc](2.0,0.3){\tiny\textsf{2.0}} \tlabel[bc](2.5,0.3){\tiny\textsf{2.5}} \tlabel[bc](3.0,0.3){\tiny\textsf{3.0}} % y-axis \tlabel[bc](0.5,-6){\rotatebox{90}{\tiny\textsf{$\log_{10}(\mbox{Mean relative error})$}}} \lines{(1,0),(1,-7)} \lines{(1.0,-1.0),(1.05,-1.0)} \lines{(1.0,-2.0),(1.05,-2.0)} \lines{(1.0,-3.0),(1.05,-3.0)} \lines{(1.0,-4.0),(1.05,-4.0)} \lines{(1.0,-5.0),(1.05,-5.0)} \lines{(1.0,-6.0),(1.05,-6.0)} \lines{(1.0,-7.0),(1.05,-7.0)} \tlabel[cr](0.95,-0.0){\tiny\textsf{0.0}} \tlabel[cr](0.95,-1.0){\tiny\textsf{-1.0}} \tlabel[cr](0.95,-2.0){\tiny\textsf{-2.0}} \tlabel[cr](0.95,-3.0){\tiny\textsf{-3.0}} \tlabel[cr](0.95,-4.0){\tiny\textsf{-4.0}} \tlabel[cr](0.95,-5.0){\tiny\textsf{-5.0}} \tlabel[cr](0.95,-6.0){\tiny\textsf{-6.0}} \tlabel[cr](0.95,-7.0){\tiny\textsf{-7.0}} % \lines{(2,-1),(2.3,-1)} \tlabel[cl](2.4,-1){\tiny\textsf{New Model}} \dashed\lines{(2,-1.8),(2.3,-1.8)} \tlabel[cl](2.4,-1.8){\tiny\textsf{NEURON}} % % Mean values at t=10 \dashed\lines{(1.2,-2.494),(3.0,-4.60)} \lines{(1.2,-2.686),(3.0,-6.466)} \end{mfpic}} \vfil \centerline{\begin{mfpic}[84][36]{0.4}{3}{-7.2}{1.3} \headlen7pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % x-axis \tlabel[br](3.0,0.7){\tiny\textsf{$\log_{10}(\mbox{No Compartments})$}} \lines{(1.0,0),(3.0,0)} \lines{(1.5,0),(1.5,-0.2)} \lines{(2.0,0),(2.0,-0.2)} \lines{(2.5,0),(2.5,-0.2)} \lines{(3.0,0),(3.0,-0.2)} \tlabel[bc](1.0,0.3){\tiny\textsf{1.0}} \tlabel[bc](1.5,0.3){\tiny\textsf{1.5}} \tlabel[bc](2.0,0.3){\tiny\textsf{2.0}} \tlabel[bc](2.5,0.3){\tiny\textsf{2.5}} \tlabel[bc](3.0,0.3){\tiny\textsf{3.0}} % y-axis \tlabel[bc](0.5,-6){\rotatebox{90}{\tiny\textsf\tiny{$\log_{10}(\mbox{Standard Dev.})$}}} \lines{(1,0),(1,-7)} \lines{(1.0,-1.0),(1.05,-1.0)} \lines{(1.0,-2.0),(1.05,-2.0)} \lines{(1.0,-3.0),(1.05,-3.0)} \lines{(1.0,-4.0),(1.05,-4.0)} \lines{(1.0,-5.0),(1.05,-5.0)} \lines{(1.0,-6.0),(1.05,-6.0)} \lines{(1.0,-7.0),(1.05,-7.0)} \tlabel[cr](0.95,-0.0){\tiny\textsf{0.0}} \tlabel[cr](0.95,-1.0){\tiny\textsf{-1.0}} \tlabel[cr](0.95,-2.0){\tiny\textsf{-2.0}} \tlabel[cr](0.95,-3.0){\tiny\textsf{-3.0}} \tlabel[cr](0.95,-4.0){\tiny\textsf{-4.0}} \tlabel[cr](0.95,-5.0){\tiny\textsf{-5.0}} \tlabel[cr](0.95,-6.0){\tiny\textsf{-6.0}} \tlabel[cr](0.95,-7.0){\tiny\textsf{-7.0}} % \lines{(2,-1),(2.3,-1)} \tlabel[cl](2.4,-1){\tiny\textsf{New Model}} \dashed\lines{(2,-1.8),(2.3,-1.8)} \tlabel[cl](2.4,-1.8){\tiny\textsf{NEURON}} % % Standard deviations at t=10 \dashed\lines{(1.2,-2.664),(3.0,-4.680)} \lines{(1.2,-3.169),(3.0,-7.021)} \end{mfpic}} \vfill \end{slide} % % \begin{slide} \centerline{\textbf{Concluding remarks}} \begin{itemize} \item At each level of discretisation the new compartmental model always performs better that the traditional model. \item This improvement in accuracy is achieved without a comparable increase in computational effort. In the simulation exercises described here, there was no discernible difference in computational effort. \item This difference in accuracy can be attributed in large part to the fact that the new model is more sensitive to the location of point input than the traditional model. \end{itemize} \end{slide} % % \begin{slide} \centerline{\textbf{Regression lines}} \textbf{Mean regressions} NEURON ($R^2=97.4\%$ (adj)) \[ \log_{10}(\mbox{MRE})=-1.09-1.17\log_{10}(\mbox{Nodes}). \] New Model ($R^2=99.5\%$ (adj)) \[ \log_{10}(\mbox{MRE})=-0.17-2.10\log_{10}(\mbox{Nodes}). \] \textbf{Standard deviations} NEURON ($R^2=98.7\%$ (adj)) \[ \log_{10}(\mbox{SD})=-1.32-1.12\log_{10}(\mbox{Nodes}). \] New Model ($R^2=99.4\%$ (adj)) \[ \log_{10}(\mbox{SD})=-0.60-2.14\log_{10}(\mbox{Nodes}) \] \end{slide} \closegraphsfile \end{document} % % \begin{slide} \begin{center} \textbf{Some additional comments} \end{center} Compartmental models of a dendrite begin with a subdivision of its sections into contiguous segments which, in turn, define the compartments of the mathematical model. \vfil Although the traditional and new compartmental models assign membrane potentials throughout a dendrite in different ways, both approaches use identical numbers of unknown potentials. \vfil The traditional and new compartmental models both involve nearest neighbour interactions, and give rise to families of differential equations that are structurally identical. \vfil The numerical solution of the ODE's requires the solution of a sparse matrix system in which the controlling matrix is time dependent. The equations can be efficiently solved by an iterative procedures. \vfill \end{slide} % % \begin{slide} \begin{center} \textbf{Analytical solution} \end{center} The deviation $V(t)$ of the somal potential from its resting value as a result of distributed current $I(x,t)$ on a uniform cylindrical dendrite of radius $a$ and length $l$ attached to a soma is \[ V(t)=e^{-t/\tau}\,\Big[\,\phi_0(t)+\sum_\beta\;\phi_\beta(t) e^{-\beta^2 t/L^2\tau}\,\cos\beta\,\Big] \] where, in the usual notation, \[ L=l\,\sqrt{\ds\frac{2 g_\mathrm{M}}{a g_\mathrm{A}}} \] and $\tau$ is the time constant of the somal and dendritic membranes (assumed identical). The summation is taken over all the non-negative solutions $\beta$ of the transcendental equation $\tan\beta+\gamma\beta=0$ where \[ \gamma=\frac{\mbox{Somal membrane leakage conductance}} {\mbox{Dendritic membrane leakage conductance}} \] \pagebreak[4] In the special case of a neuron, initially at its resting potential, and stimulated by point currents $I_k(t)$ at distance $x_k$ from the soma of the uniform cylinder ($k=1,\cdots,n$), the coefficient functions $\phi_0$ and $\phi_\beta$ satisfy \[ \begin{array}{rcl} \ds\frac{d\phi_0}{dt} & = &\ds -\frac{e^{t/\tau}} {C_\mathrm{D}+C_\mathrm{S}}\,\Bigg[\, I_\mathrm{S}(t)+\sum_{k=1}^n\;I_k(t)\,\Bigg]\,,\\[25pt] \ds\frac{d\phi_\beta}{dt} & = & \ds-\frac{2e^{(1+\beta^2/L^2)t/\tau}} {C_\mathrm{D}+C_\mathrm{S}\cos^2\beta}\,\times\\[20pt] &&\hskip-20pt\ds\Bigg[\, \sum_{k=1}^n \;I_k(t)\cos\beta\big(1-x_k/l\big) +\cos\beta\,I_\mathrm{S}(t)\,\Bigg]\,. \end{array} \] The parameters $C_\mathrm{D}$ and $C_\mathrm{S}$ denote respectively the total membrane capacitances of the soma and dendrite, and $I_\mathrm{S}(t)$ is the current supplied to the soma. \end{slide} % % \begin{slide} \begin{center} \textbf{Use of the analytical solution} \end{center} New and traditional compartmental models (the latter represented by the NEURON simulator) were compared by estimating the accuracy with which both models computed the time course of the potential at the soma of the model neuron under the action of large scale exogenous input on its dendrites. Facts. \textbf{The connected cable} of the model neuron is equivalent to a cylinder (Rall cylinder). \textbf{The effect} of any configuration of exogenous input at the soma of the model neuron (assumed to be a sphere of diameter $40\,\mu$m) is exactly representable at the soma of the equivalent cylinder by a suitable configuration of exogenous input on that cylinder. \textbf{Each input} on the model neuron is mapped to an input on the equivalent cylinder of identical strength and lying at the same electrotonic distance from the soma of the equivalent cylinder as the original input lies from the soma of the model neuron. \vfill \end{slide}