\section{Distributed and point process input to a segment}\label{dpi} In general, segments receive distributed and point process sources of input each of which require a different mathematical treatment. The current supplied by distributed input such as intrinsic voltage-dependent current or capacitative current is proportional to the surface area of the segment on which it acts, whereas the current supplied to a segment at a synapse or by an exogenous point input is independent of the size of the segment. An implicit assumption of a compartmental model is that distributed current input to a segment is small by comparison with axial current flowing along the segment. To appreciate why this assumption is reasonable, consider a cylindrical dendritic segment of radius $r$ (cm), length $h$ (cm) and with membrane of constant conductance $g_\mathrm{M}$ (mS/cm$^2$). Suppose that axoplasm has constant conductance $g_\mathrm{A}$ (mS/cm) and that a potential difference $V$ (mV) exists between the segment boundaries, then the axial current along the segment is $I_\mathrm{A}=\pi r^2 g_\mathrm{A} V/h$ ($\mu$A) and the total distributed current crossing the membrane of the segment is $I_\mathrm{M}=2\pi r h g_\mathrm{M}\,(V/2)$. The ratio of the distributed current to the axial current is therefore \begin{equation}\label{pc1} \frac{\mbox{Distributed current}}{\mbox{Axial current}} =\frac{I_\mathrm{M}}{I_\mathrm{A}}=\frac{\pi r h g_\mathrm{M}\,V} {\pi r^2 g_\mathrm{A}\,(V/h)}=\frac{h^2 g_\mathrm{M}} {r g_\mathrm{A}}=\Big(\frac{h}{r}\Big)^2\, \frac{r g_\mathrm{M}}{g_\mathrm{A}}\,. \end{equation} For a typical dendritic segment $r g_\mathrm{M}/g_\mathrm{A}$ is small (say $ \approx 10^{-5}$), and therefore distributed current acting on a segment is small by comparison with axial current for ``short'' segments. On the other hand, segments several orders of magnitude longer than their radius can be expected to have distributed and axial currents of similar magnitude. An important property of a compartmental model is that segments are not excessively long by comparison with their radius. (However, see Segev and Burke, \cite{Segev98}, Figure 3.3b). In the treatment of distributed current, the development of the new compartmental model makes explicit use of the assumption that distributed current is much smaller than axial current. This assumption may not be valid for point process input, and will not be made for the treatment of this type of input in the new approach to compartmental modelling. \subsection{Axial current in the absence of transmembrane current} The importance of the conclusion from Section \ref{dpi} is that distributed transmembrane current acting on short segments is small compared with axial current, and may be neglected in a first approximation of the distribution of membrane potential on a segment. Thus in the absence of point process input, the axial current in a segment is well approximated from the potential drop across the segment. In the light of this approximation, consider Figure \ref{model} which illustrates a dendritic segment of length $h$ in which $\lambda\in[0,1]$ is the fractional distance of a point of the segment from its proximal end ($\lambda=0$). Let $r_\mathrm{P}$ and $r_\mathrm{D}$ be the radii of the segment at its proximal and distal boundaries respectively, let $V_\mathrm{P}(t)$ and $V_\mathrm{D}(t)$ be the membrane potentials at these boundaries and let $I_\mathrm{PD}$ be the axial current in the segment in the absence of transmembrane current. \begin{figure}[!h] \centering \begin{tabular}{c} \includegraphics[ ]{NCFig2.eps} \end{tabular}\qquad \begin{tabular}{p{2.55in}} \caption{\label{model} A segment of length $h$ is illustrated. In the absence of transmembrane current, membrane potentials $V_\mathrm{P}$ and $V_\mathrm{D}$ at the proximal and distal boundaries of the segment generate axial current $I_\mathrm{PD}$.} \end{tabular} \end{figure} %\begin{figure}[!h] %\centering %\begin{tabular}{c} %\begin{mfpic}[1][1]{-40}{140}{180}{300} %\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} %\end{tabular}\qquad %\begin{tabular}{p{2.55in}} %\caption{\label{model} A segment of length $h$ (cm) is illustrated. In %the absence of transmembrane current, membrane potentials $V_\mathrm{P}$ %and $V_\mathrm{D}$ at the proximal and distal boundaries of the %segment generate axial current $I_\mathrm{PD}$.} %\end{tabular} %\end{figure} The membrane of the segment in Figure \ref{model} is formed by rotating the straight line PD about the axis of the dendrite to form the frustum of a cone of radius \begin{equation}\label{mp1} r(\lambda)=(1-\lambda)r_\mathrm{P}+\lambda r_\mathrm{D} \,,\qquad \lambda\in[0,1]\,. \end{equation} Assuming that the segment is filled with axoplasm of constant conductance $g_\mathrm{A}$ and that no current crosses its membrane, then the relationship between $V_\mathrm{P}$, $V_\mathrm{D}$ and $I_\mathrm{PD}$ can be constructed by integrating the defining equation of axial current, namely $I_\mathrm{PD}=-g_\mathrm{A}\,A(x)\,dV/dx$, from the proximal to the distal boundary of a segment. For the conical segment illustrated in Figure \ref{model}, $A(x)=\pi r^2(\lambda)$, $dV/dx=h^{-1}\,dV/d\lambda$ and the equation to be integrated is \[ I_\mathrm{PD}=-\frac{g_\mathrm{A}\pi}{h}\,\Big[\, (1-\lambda)r_\mathrm{P}+\lambda r_\mathrm{D}\,\Big]^2\, \frac{dV}{d\lambda} \] with boundary conditions $V(0)=V_\mathrm{P}$ and $V(1)=V_\mathrm{D}$. The result of this calculation is that the the axial current $I_\mathrm{PD}$ and the potentials $V_\mathrm{P}$ and $V_\mathrm{D}$ are connected by the formula \begin{equation}\label{mp2} I_\mathrm{PD}= \frac{\pi g_\mathrm{A} r_\mathrm{P} r_\mathrm{D}}{h}\,\big(\,V_\mathrm{P}-V_\mathrm{D}\,\big) \end{equation} in the absence of transmembrane current. Moreover, the potential at the point $\lambda$ is \begin{equation}\label{mp3} 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{equation} Note that equation (\ref{mp3}) is valid for sections with taper and in the absence of taper will lead to a membrane potential which varies linearly along the length of a segment. The subsequent development of the new compartmental model assumes that sections may taper unless stated specifically that the section is uniform. \subsection{Partitioning rule for transmembrane current} In compartmental modelling the effect of transmembrane current is represented in the model by input at points, or nodes, at which the membrane potential is known. In a traditional approach to compartmental modelling, these nodes are at the centre of segments, whereas in the new approach they are located at the boundaries of segments. The new approach partitions the effect of input at any location between the nodes at the proximal and distal boundaries of the segment. This procedure ensures that the solution of the compartmental model is insensitive to small changes in the location of segment boundaries because changes in these boundaries also affect how the input is partitioned between nodes. In the mathematical description of the new compartmental model, the effect of input to a segment is treated as perturbations $I_\mathrm{P}$ and $I_\mathrm{D}$ to the axial current $I_\mathrm{PD}$ at the proximal and distal boundaries of a segment. Axial current $I_\mathrm{PD}+I_\mathrm{P}$ is assumed to leave the proximal boundary of a segment in the direction of its distal boundary, while axial current $I_\mathrm{PD}+I_\mathrm{D}$ is assumed to arrive at the distal boundary of a segment from the direction of its proximal boundary. The perturbations $I_\mathrm{P}$ and $I_\mathrm{D}$ must satisfy the conservation of current condition \begin{equation}\label{potc1} (I_\mathrm{PD}+I_\mathrm{D})-(I_\mathrm{PD}+I_\mathrm{P})+h\int_0^1 J(\lambda,t)\,d\lambda=0\quad\rightarrow\quad I_\mathrm{P}-I_\mathrm{D}=h\int_0^1 J(\lambda,t)\,d\lambda \end{equation} where $J(\lambda,t)$ denotes transmembrane current. The task is to construct expressions for $I_\mathrm{P}$ and $I_\mathrm{D}$ that satisfy (\ref{potc1}) for all constitutive forms for the current density $J(\lambda,t)$. The new approach to compartmental modelling requires a procedure or rule for partitioning transmembrane current between the proximal and distal boundaries of a segment. The rule used in this article is that transmembrane current flow to a boundary of a segment is proportional to the axial conductance of the segment lying between the point of application of the current and that boundary. If $G_\mathrm{P}(\lambda)$ is the axial conductance of the portion of segment lying between the point $\lambda$ and the proximal boundary of the segment, and $G_\mathrm{D}(\lambda)$ is the axial conductance of the portion of segment lying between the point $\lambda$ and the distal boundary of the segment, then \begin{equation}\label{potc2} G_\mathrm{P}(\lambda) = \frac{\pi g_\mathrm{A} r_\mathrm{P}r(\lambda)}{\lambda h}\,,\qquad G_\mathrm{D}(\lambda) = \frac{\pi g_\mathrm{A} r_\mathrm{D} r(\lambda)}{(1-\lambda)h} \end{equation} and the rule for partitioning transmembrane current leads to the expressions \begin{equation}\label{potc3} \begin{array}{rcl} I_\mathrm{P} & = & \ds h\int_0^1 \frac{G_\mathrm{P} J(\lambda,t)\,d\lambda} {G_\mathrm{P}+G_\mathrm{D}} = h\int_0^1 \frac{(1-\lambda)\,r_\mathrm{P}\, J(\lambda,t)\,d\lambda}{(1-\lambda)\,r_\mathrm{P} +\lambda\,r_\mathrm{D}}\,,\\[10pt] -I_\mathrm{D} & = & \ds h\int_0^1 \frac{G_\mathrm{D} J(\lambda,t)\,d\lambda} {G_\mathrm{P}+G_\mathrm{D}} = 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} \end{equation} Clearly these expressions satisfy identically condition (\ref{potc1}) for the conservation of current. \subsection{Specification of transmembrane current} Transmembrane current is usually assumed to consist of four distinct components: capacitative current, intrinsic voltage-dependent current and point process input which is subdivided into synaptic current and exogenous point current. Total transmembrane current is represented by \begin{equation}\label{tc1} \int 2\pi r \,c_\mathrm{M}\,\frac{\partial V}{\partial t}\,dx +\int 2\pi r\,J_\mathrm{IVDC}(V)\,dx+\sum J_\mathrm{SYN}(V_\mathrm{syn}) +\sum I_\mathrm{EX} \end{equation} where the integrals and summations are taken over the length of a segment. In this expression $c_\mathrm{M}$ ($\mu$F/cm$^2$) is the specific capacitance of the segment membrane, $V(x,t)$ is the distribution of membrane potential at time $t$ (msec), $J_\mathrm{IVDC}(V)$ ($\mu$A/cm$^2$) is the density of transmembrane current due to intrinsic voltage-dependent channel activity, $J_\mathrm{SYN}(V_\mathrm{syn})$ ($\mu$A) describes synaptic input and $I_\mathrm{EX}$ ($\mu$A) describes exogenous input. Although the specific capacitance of dendritic membrane is normally taken to be constant in neuronal modelling, it will be treated here as a function of position to show how transmembrane current of this type may be incorporated into the new compartmental model. For a segment of length $h$, the expression for $J(\lambda,t)$ corresponding to formula (\ref{tc1}) is \begin{equation}\label{tc2} \begin{array}{rcl} h J(\lambda,t) & = & \ds 2\pi h r(\lambda)\,c_\mathrm{M}(\lambda)\,\frac{\partial V(\lambda,t)}{\partial t}+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) + \sum_k I_\mathrm{EX}(t)\,\delta(\lambda-\lambda_k) \end{array} \end{equation} where $\lambda_k$ denotes the relative location of the $k^{th}$ synapse or exogenous input with respect to the proximal boundary of the segment ($\lambda=0$).