Abstract

For large-scale network simulations, it is often desirable to have computationally tractable, yet in a defined sense still physiologically valid neuron models. In particular, these models should be able to reproduce physiological measurements, ideally in a predictive sense, and under different input regimes in which neurons may operate in vivo. Here we present an approach to parameter estimation for a simple spiking neuron model mainly based on standard f–I curves obtained from in vitro recordings. Such recordings are routinely obtained in standard protocols and assess a neuron’s response under a wide range of mean-input currents. Our fitting procedure makes use of closed-form expressions for the firing rate derived from an approximation to the adaptive exponential integrate-and-fire (AdEx) model. The resulting fitting process is simple and about two orders of magnitude faster compared to methods based on numerical integration of the differential equations. We probe this method on different cell types recorded from rodent prefrontal cortex. After fitting to the f–I current-clamp data, the model cells are tested on completely different sets of recordings obtained by fluctuating (“in vivo-like”) input currents. For a wide range of different input regimes, cell types, and cortical layers, the model could predict spike times on these test traces quite accurately within the bounds of physiological reliability, although no information from these distinct test sets was used for model fitting. Further analyses delineated some of the empirical factors constraining model fitting and the model’s generalization performance. An even simpler adaptive LIF neuron was also examined in this context. Hence, we have developed a “high-throughput” model fitting procedure which is simple and fast, with good prediction performance, and which relies only on firing rate information and standard physiological data widely and easily available.

Highlights

  • We investigated a large number of data sets (N ∼ 100 recorded prefrontal cortex neurons) in order to characterize the potential of our simplified AdEx model

  • The fitting procedure is based on closed-form expressions for the f–I curves we had derived from an approximation to the AdEx model, and does not require to simulate the full underlying system of differential equations up to the point where a steady-state in spiking activity has been reached

  • For the purpose of large-scale neuronal network simulations (Traub et al, 1988, 2005; Markram et al, 2004; Markram, 2006; Wang et al, 2006; Izhikevich and Edelman, 2008; Lansner, 2009), single neuron models which do not compromise physiological realism too much and capture some of the tremendous cellular heterogeneity observed in real cortical tissue are of increasing interest

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Summary

Introduction

In recent years there has been a growing interest in large-scale neuronal network simulations (Traub et al, 1988, 2005; Whittington et al, 2000; Markram, 2006; Izhikevich and Edelman, 2008; Lansner, 2009; Lundqvist et al, 2010) that capture the cellular heterogeneity observed in real cortical tissue (Binzegger et al, 2004; Markram et al, 2004; Wang et al, 2006; Thomson and Lamy, 2007) and model interactions between many diverse cortical and subcortical brain structures (Lansner et al, 2003; Izhikevich and Edelman, 2008). On one side, detailed multi-compartmental biophysically meaningful models can often reproduce voltage traces of their experimental counterparts to almost arbitrary degree (Traub et al, 1991; De Schutter and Bower, 1994; Jaeger et al, 1997; Poirazi and Mel, 2001; Prinz et al, 2003; Druckmann et al, 2007, 2011; Moyer et al, 2007), and potentially provide a deep understanding of the underlying biophysical mechanisms and functional role of the cellular morphology (e.g., Mainen and Sejnowski, 1996; Poirazi and Mel, 2001; Shu et al, 2006; Durstewitz and Gabriel, 2007) Because of their large number of parameters, fitting such single-cell models to electrophysiological observations is often a slow and tedious procedure which may run into the risk of serious over-fitting: Different parameter configurations may result in good fits of a given “training set” (Prinz et al, 2004), Frontiers in Computational Neuroscience www.frontiersin.org

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