High-density MEA recordings unveil the dynamics of bursting events in Cell Cultures

High density multielectrode arrays (MEAs) based on CMOS technology (CMOS-MEAs) can simultaneously record extracellular spiking activity in neuronal cultures from 4096 closely spaced microelectrodes. This allows for a finer investigation of neuronal network activity compared to conventional MEAs with a few tens of electrodes. However, the sensing properties of these devices differ. To highlight this aspect, here we investigate and discuss the differences observed when quantifying spontaneous synchronized bursting events (SBEs) in datasets acquired with conventional MEAs and high-density MEAs from comparable hippocampal cultures. We found that datasets acquired with high-density MEAs exhibit collective dynamics similar to conventional arrays, but are characterized by a higher percentage of random spikes, i.e. spikes that are not part of a burst, most probably resulting from the larger recording capability. Additionally, the percentage of electrodes that record a burst is remarkably small on high-density MEAs compared to what can be observed on conventional MEAs and SBEs appear to be propagating in time across the electrode array, by involving shorter sequences of spikes per electrode. Overall, these results highlight a lower level of network synchronization involved in SBEs compared to what has been debated for several decades based on conventional MEA recordings from cell cultures.

[1]  M Gandolfo,et al.  Tracking burst patterns in hippocampal cultures with high-density CMOS-MEAs , 2010, Journal of neural engineering.

[2]  R. Segev,et al.  Long term behavior of lithographically prepared in vitro neuronal networks. , 2002, Physical review letters.

[3]  Alessandro Vato,et al.  Burst detection algorithms for the analysis of spatio-temporal patterns in cortical networks of neurons , 2005, Neurocomputing.

[4]  Paolo Massobrio,et al.  A novel algorithm for precise identification of spikes in extracellularly recorded neuronal signals , 2009, Journal of Neuroscience Methods.

[5]  Luca Berdondini,et al.  Emergent Functional Properties of Neuronal Networks with Controlled Topology , 2012, PloS one.

[6]  Eshel Ben-Jacob,et al.  Collective Plasticity and Individual Stability in Cultured Neuronal Networks , 2006 .

[7]  Luca Berdondini,et al.  High-density MEAs reveal lognormal firing patterns in neuronal networks for short and long term recordings , 2015, 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER).

[8]  Luca Berdondini,et al.  Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks. , 2009, Lab on a chip.

[9]  L. M. Prida,et al.  Nonlinear frequency-dependent synchronization in the developing hippocampus. , 1999, Journal of neurophysiology.

[10]  György Buzsáki,et al.  Neural Syntax: Cell Assemblies, Synapsembles, and Readers , 2010, Neuron.

[11]  Luca Berdondini,et al.  Experimental Investigation on Spontaneously Active Hippocampal Cultures Recorded by Means of High-Density MEAs: Analysis of the Spatial Resolution Effects , 2010, Front. Neuroeng..