meaRtools: An R package for the analysis of neuronal networks recorded on microelectrode arrays

Abstract

Here we present an open-source R package ‘meaRtools’ that provides a platform for analyzing neuronal networks recorded on Microelectrode Arrays (MEAs). Cultured neuronal networks monitored with MEAs are now being widely used to characterize in vitro models of neurological disorders and to evaluate pharmaceutical compounds. meaRtools provides core algorithms for MEA spike train analysis, feature extraction, statistical analysis and plotting of multiple MEA recordings with multiple genotypes and treatments. meaRtools functionality covers novel solutions for spike train analysis, including algorithms to assess electrode cross-correlation using the spike train tiling coefficient (STTC), mutual information, synchronized bursts and entropy within cultured wells. Also integrated is a solution to account for bursts variability originating from mixed-cell neuronal cultures. The package provides a statistical platform built specifically for MEA data that can combine multiple MEA recordings and compare extracted features between different genetic models or treatments. We demonstrate the utilization of meaRtools to successfully identify epilepsy-like phenotypes in neuronal networks from Celf4 knockout mice. The package is freely available under the GPL license (GPL> = 3) and is updated frequently on the CRAN web-server repository. The package, along with full documentation can be downloaded from: https://cran.r-project.org/web/packages/meaRtools/.

Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy

“…Raw data and spike list files were collected. Spike list files were used to extract additional spike, burst, and network features, using a custom MEA analysis software package for interpretation of neuronal activity patterns, meaRtools, based on rigorous permutation statistics that enables enhanced identification of over 70 activity features ( Gelfman et al, 2018 ). Specifically, we analyzed spiking and bursting rates, burst duration, and the time between bursts (i.e., interburst interval, IBI), as well as synchronicity of the network.…”

Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures

“…Burst analysis was performed utilizing the R-package meaRtools 85 . For burst detection, the logISI algorithm was integrated into the analysis code 86 with minor modifications.…”

A Transcriptome‐Based Drug Discovery Paradigm for Neurodevelopmental Disorders

“…Importantly, mouse models can often provide disease-relevant behavioral and electrophysiological endpoints for small molecule screening. 2,[57][58][59][60] Some mouse models of genetic epilepsies, for example, display spontaneous seizures or altered seizure thresholds. Additionally, although mouse models cannot fully capture the symptoms associated with ASD and schizophrenia, they can model certain aspects of these disorders that may manifest in a similar manner in rodents.…”

“…Genetically engineered mouse lines have contributed to significant advances in neurodevelopmental disease gene research. Importantly, mouse models can often provide disease‐relevant behavioral and electrophysiological endpoints for small molecule screening 2,57–60 . Some mouse models of genetic epilepsies, for example, display spontaneous seizures or altered seizure thresholds.…”