Abstract

Advanced statistical methods have enabled trial-by-trial inference of the underlying excitatory and inhibitory synaptic conductances (SCs) of membrane-potential recordings. Simultaneous inference of both excitatory and inhibitory SCs sheds light on the neural circuits underlying the neural activity and advances our understanding of neural information processing. Conventional Bayesian methods can infer excitatory and inhibitory SCs based on a single trial of observed membrane potential. However, if multiple recorded trials are available, this typically leads to suboptimal estimation because they neglect common statistics (of synaptic inputs (SIs)) across trials. Here, we establish a new expectation maximization (EM) algorithm that improves such single-trial Bayesian methods by exploiting multiple recorded trials to extract common SI statistics across the trials. In this paper, the proposed EM algorithm is embedded in parallel Kalman filters or particle filters for multiple recorded trials to integrate their outputs to iteratively update the common SI statistics. These statistics are then used to infer the excitatory and inhibitory SCs of individual trials. We demonstrate the superior performance of multiple-trial Kalman filtering (MtKF) and particle filtering (MtPF) relative to that of the corresponding single-trial methods. While relative estimation error of excitatory and inhibitory SCs is known to depend on the level of current injection into a cell, our numerical simulations using MtKF show that both excitatory and inhibitory SCs are reliably inferred using an optimal level of current injection. Finally, we validate the robustness and applicability of our technique through simulation studies, and we apply MtKF to in vivo data recorded from the rat barrel cortex.

Highlights

  • Inferring the excitatory and inhibitory synaptic conductances (SCs) from single trials of membrane-potential recordings, and their underlying trial-to-trial variability, is crucial for understanding various functional aspects of neuronal sensory response, such as the neuron’s receptive fields (Anderson et al, 2001; Wehr and Zador, 2003; Priebe and Ferster, 2005) or unveiling the mechanisms of adaptation (Katz et al, 2006; Heiss et al, 2008; Ramirez et al, 2014)

  • We first simulate the membranepotential dynamics with zero current injection to compare the performance of multiple-trial Kalman filtering (MtKF) with that of single-trial KF (StKF) (Lankarany et al, 2013b)

  • We proposed a new multiple-trial expectation maximization (EM) framework to simultaneously infer the excitatory and inhibitory SCs in individual trials from the recorded membrane potential (MP)

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Summary

Introduction

Inferring the excitatory and inhibitory synaptic conductances (SCs) from single trials of membrane-potential recordings, and their underlying trial-to-trial variability, is crucial for understanding various functional aspects of neuronal sensory response, such as the neuron’s receptive fields (Anderson et al, 2001; Wehr and Zador, 2003; Priebe and Ferster, 2005) or unveiling the mechanisms of adaptation (Katz et al, 2006; Heiss et al, 2008; Ramirez et al, 2014). While the voltage-clamp technique (Zhang et al, 2003; Murphy and Rieke, 2006; Haider et al, 2013) can yield either excitatory or inhibitory SCs in each trial by setting the holding potential equal to the inhibitory or excitatory reversal potential, respectively, simultaneous recording of both SCs is not possible

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