Many different types of integrate-and-fire models have been designed in order to explain how it is possible for a cortical neuron to integrate over many independent inputs while still producing highly variable spike trains. Within this context, the variability of spike trains has been almost exclusively measured using the coefficient of variation of interspike intervals. However, another important statistical property that has been found in cortical spike trains and is closely associated with their high firing variability is long-range dependence. We investigate the conditions, if any, under which such models produce output spike trains with both interspike-interval variability and long-range dependence similar to those that have previously been measured from actual cortical neurons. We first show analytically that a large class of high-variability integrate-and-fire models is incapable of producing such outputs based on the fact that their output spike trains are always mathematically equivalent to renewal processes. This class of models subsumes a majority of previously published models, including those that use excitation-inhibition balance, correlated inputs, partial reset, or nonlinear leakage to produce outputs with high variability. Next, we study integrate-and-fire models that have (non-Poissonian) renewal point process inputs instead of the Poisson point process inputs used in the preceding class of models. The confluence of our analytical and simulation results implies that the renewal-input model is capable of producing high variability and long-range dependence comparable to that seen in spike trains recorded from cortical neurons, but only if the interspike intervals of the inputs have infinite variance, a physiologically unrealistic condition. Finally, we suggest a new integrate-and-fire model that does not suffer any of the previously mentioned shortcomings. By analyzing simulation results for this model, we show that it is capable of producing output spike trains with interspike-interval variability and long-range dependence that match empirical data from cortical spike trains. This model is similar to the other models in this study, except that its inputs are fractional-gaussian-noise-driven Poisson processes rather than renewal point processes. In addition to this model's success in producing realistic output spike trains, its inputs have longrange dependence similar to that found in most subcortical neurons in sensory pathways, including the inputs to cortex. Analysis of output spike trains from simulations of this model also shows that a tight balance between the amounts of excitation and inhibition at the inputs to cortical neurons is not necessary for high interspike-interval variability at their outputs. Furthermore, in our analysis of this model, we show that the superposition of many fractional-gaussian-noise-driven Poisson processes does not approximate a Poisson process, which challenges the common assumption that the total effect of a large number of inputs on a neuron is well represented by a Poisson process.

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