Quantification of bursting and synchrony in cultured hippocampal neurons

Abstract

It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavior such as seizures. However, methods for quantifying bursting and synchrony are not agreed upon and can be confounded with spike rate measures. Previous validation has largely relied on in silico networks and single experimental conditions. How published measures of bursting and synchrony perform when applied to biological networks of varied average spike rate and subjected to varied experimental challenges is unclear. In multielectrode array recordings of network activity, we found that two mechanistically distinct drugs, cyclothiazide and bicuculline, produced equivalent increases in average spike rate but differed in bursting and synchrony. We applied several measures of bursting to the recordings (2 threshold interval methods and a surprise-based method) and found that a measure based on an average critical interval, adjusted for the array-wide spike rate, performed best in quantifying differential drug effects. To quantify synchrony, we compared a coefficient of variation-based measure, the recently proposed spike time tiling coefficient, the SPIKE-distance measure, and a global synchrony index. The spike time tiling coefficient, the SPIKE-distance measure, and the global synchrony index all captured a difference between drugs with the best performance exhibited by the global synchrony index. In summary, our exploration should aid other investigators by highlighting strengths and limitations of current methods.

A comparison of computational methods for detecting bursts in neuronal spike trains and their application to human stem cell-derived neuronal networks

“…For example, the RGS method, which was originally developed to analyze dopaminergic neurons, could not detect the majority of bursts in simulated spike trains and also performed poorly at analyzing experimental recordings from mouse RGCs, even when its probabilistic threshold parameter was varied over a large range. Other studies have also found issues using the RGS method to analyze changes in bursting behavior under different drug effects ( Eisenman et al 2015 ).…”

“…MEAs have thus been used to study changes in the spontaneous activity patterns exhibited by neuronal networks over development ( Charlesworth et al 2015 ; Wagenaar et al 2006 ). Analysis of bursting activity has also been used as an important tool in applications such as studying the impact of genetic or chemical manipulations on network activity ( Charlesworth et al 2016 ; Eisenman et al 2015 ).…”

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents

“…Furthermore, while multiple studies have investigated the role of these synaptic receptors in spike train generation (Chiappalone et al 2007; Eisenman et al 2015;Madha-van et al 2007;Slomowitz et al 2015;Wagenaar et al 2006), the relationship between the low-frequency component of the local field potential (LFP) and spike generation, under different synaptic connectivity conditions, has not been well understood. Ultimately, such detailed knowledge of the role of synaptic transmission and the low-frequency components of the LFP may help us to better interpret activity recorded at a larger scale, such as the electroencephalogram (EEG).…”

Comparison of Different Spike Train Synchrony Measures Regarding Their Robustness to Erroneous Data From Bicuculline-Induced Epileptiform Activity

“…Measuring synchrony between neural spike trains is a common method to analyze experimental data e.g. recordings from in vitro neuronal cell cultures with microelectrode arrays (MEA) (Selinger et al, 2004;Chiappalone et al, 2006Chiappalone et al, , 2007aEisenman et al, 2015;Flachs and Ciba, 2016) or from in vivo experiments (Li et al, 2011). As an example for in vitro neuronal cell cultures on MEA chips, Sokal et al (2000) reported that synchrony reliably increased due to the substance bicuculline (BIC), while the usual applied quantification method "spike rate" increased or decreased.…”