%0 Journal Article %A Robert P. Gowers %A Yulia Timofeeva %A Magnus J. E. Richardson %T Low-rate firing limit for neurons with axon, soma and dendrites driven by spatially distributed stochastic synapses %D 2019 %R 10.1101/669705 %J bioRxiv %P 669705 %X Analytical forms for neuronal firing rates are important theoretical tools for the analysis of network states. Since the 1960s, the majority of approaches have treated neurons as being electrically compact and therefore isopotential. These approaches have yielded considerable insight into how single-cell properties affect network activity; however, many neuronal classes, such as cortical pyramidal cells, are electrically extended objects. Calculation of the complex flow of electrical activity driven by stochastic spatio-temporal synaptic input streams in these structures has presented a significant analytical challenge. Here we demonstrate that an extension of the level-crossing method of Rice, previously used for compact cells, provides a general framework for approximating the firing rate of neurons with spatial structure. Even for simple models, the analytical approximations derived demonstrate a surprising richness including: independence of the firing rate to the electrotonic length for certain models, but with a form distinct to the point-like leaky integrate-and-fire model; a non-monotonic dependence of the firing rate on the number of dendrites receiving synaptic drive; a significant effect of the axonal and somatic load on the firing rate; and the role that the trigger position on the axon for spike initiation has on firing properties. The approach necessitates only calculating first and second moments of the non-thresholded voltage and its rate of change in neuronal structures subject to spatio-temporal synaptic fluctuations. The combination of simplicity and generality promises a framework that can be built upon to incorporate increasing levels of biophysical detail and extend beyond the low-rate firing limit treated in this paper.Author summary Neurons are extended cells with multiple branching dendrites, a cell body and an axon. In an active neuronal network, neurons receive vast numbers of incoming synaptic pulses throughout their dendrites and cell body that each exhibit significant variability in amplitude and arrival time. The resulting synaptic input causes voltage fluctuations throughout their structure that evolve in space and time. The dynamics of how these signals are integrated and how they ultimately trigger outgoing spikes have been modelled extensively since the late 1960s. However, until relatively recently the ma jority of the mathematical formulae describing how fluctuating synaptic drive triggers action potentials have been applicable only for small neurons with the dendritic and axonal structure ignored. This has been largely due to the mathematical complexity of including the effects of spatially distributed synaptic input. Here we show that in a physiologically relevant, low-firing-rate regime, an approximate, level-crossing approach can be used to provide an estimate for the neuronal firing rate even when the dendrites and axons are included. We illustrate this approach using basic neuronal morphologies that capture the fundamentals of neuronal structure. Though the models are simple, these preliminary results show that it is possible to obtain useful formulae that capture the effects of spatially distributed synaptic drive. The generality of these results suggests they will provide a mathematical framework for future studies that might require the structure of neurons to be taken into account, such as the effect of electrical fields or multiple synaptic input streams that target distinct spatial domains of cortical pyramidal cells. %U https://www.biorxiv.org/content/biorxiv/early/2019/06/12/669705.full.pdf