Stimulus-evoked high frequency oscillations are present in neuronal networks on microelectrode arrays

Hales, Chadwick M.; Zeller-Townson, Riley; Newman, Jonathan P.; Shoemaker, James T.; Killian, Nathaniel J.; Potter, Steve M.

doi:10.3389/fncir.2012.00029

Cited by 14 publications

(21 citation statements)

References 62 publications

(117 reference statements)

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“…Our recordings in cortical cells cultured on microelectrode arrays (MEAs) confirmed the data presented by Hales et al. (): Electrical stimulation evoked voltage oscillations in a broad and continuous frequency spectrum up to 600 Hz. The amplitudes of these oscillations were comparable to extracellularly measured neuronal action potentials.…”

Section: Resultssupporting

confidence: 89%

High-frequency voltage oscillations in cultured astrocytes

et al. 2015

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Because of their close interaction with neuronal physiology, astrocytes can modulate brain function in multiple ways. Here, we demonstrate a yet unknown astrocytic phenomenon: Astrocytes cultured on microelectrode arrays (MEAs) exhibited extracellular voltage fluctuations in a broad frequency spectrum (100–600 Hz) after electrical stimulation. These aperiodic high-frequency oscillations (HFOs) could last several seconds and did not spread across the MEA. The voltage-gated calcium channel antagonist cilnidipine dose-dependently decreased the power of the oscillations. While intracellular calcium was pivotal, incubation with bafilomycin A1 showed that vesicular release of transmitters played only a minor role in the emergence of HFOs. Gap junctions and volume-regulated anionic channels had just as little functional impact, which was demonstrated by the addition of carbenoxolone (100 μmol/L) and NPPB (100 μmol/L). Hyperpolarization with low potassium in the extracellular solution (2 mmol/L) dramatically raised oscillation power. A similar effect was seen when we added extra sodium (+50 mmol/L) or if we replaced it with NMDG+ (50 mmol/L). The purinergic receptor antagonist PPADS suppressed the oscillation power, while the agonist ATP (100 μmol/L) had only an increasing effect when the bath solution pH was slightly lowered to pH 7.2. From these observations, we conclude that astrocytic voltage oscillations are triggered by activation of voltage-gated calcium channels and driven by a downstream influx of cations through channels that are permeable for large ions such as NMDG+. Most likely candidates are subtypes of pore-forming P2X channels with a low affinity for ATP.

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Section: Resultssupporting

confidence: 89%

High-frequency voltage oscillations in cultured astrocytes

et al. 2015

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“…Across the entire culture, within 100 ms of stimulation, an increase in signal power around 350 Hz was seen compared to the 100 ms preceding stimulation (Figure 6C ; P < 0.05, cluster-based permutation test; Maris and Oostenveld, 2007 ). Interestingly, this is near the peak frequency of the stimulus-induced oscillation described in Hales et al ( 2012 ), suggesting that it may have arisen through a similar mechanism. The oscillation described in Hales et al ( 2012 ) was restricted to the stimulated electrodes, whereas the result described here was observed over a population of recordings sites, suggesting that it may reflect propagating multi-unit activity (MUA).…”

Section: Resultssupporting

confidence: 58%

“…Interestingly, this is near the peak frequency of the stimulus-induced oscillation described in Hales et al ( 2012 ), suggesting that it may have arisen through a similar mechanism. The oscillation described in Hales et al ( 2012 ) was restricted to the stimulated electrodes, whereas the result described here was observed over a population of recordings sites, suggesting that it may reflect propagating multi-unit activity (MUA). However, there remained a significant increase in high-frequency signal power even after removing the effect of spikes by replacing ±3 ms around spike times (detected at ± 3 standard deviations of the raw signal and resolved at 1 kHz) with the mean value during each snippet.…”

Section: Resultssupporting

confidence: 58%

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

et al. 2016

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Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.

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“…The aim of this study was to provide insight into the kinds of neural dynamics that explain how synchronized bursts of neural activity can disrupt cognitive processing. Because of advances in stem cell technology, the development of new in vitro models of basic processes relevant to cognitive and neurological disorders has become increasingly relevant (Chiappalone et al, 2003 ; Berger et al, 2011 ; Durnaoglu et al, 2011 ; Hales et al, 2012 ; Stephens et al, 2012 ). The ability to culture human neurons derived from patients with neurological diseases and to test those cells using in vitro drug protocols will help researchers develop individualized treatments for patients and perhaps even aid in the development of new drugs for controlling negative symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Synchronous Network Bursts (SNBs) arise spontaneously in cultures of living neuronal networks and appear to be an intrinsic property of any densely connected recurrent neural network (Wagenaar et al, 2005 ; Chiappalone et al, 2009 ; Hales et al, 2012 ; Maheswaranathan et al, 2012 ). Given that cultured neuronal networks can maintain stimulus-specific information across short delays, two experiments were performed to test whether this information is disrupted by SNBs.…”

Section: Introductionmentioning

confidence: 99%

Stimulus information stored in lasting active and hidden network states is destroyed by network bursts

Dranias

Westover

Cash

et al. 2015

Front. Integr. Neurosci.

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In both humans and animals brief synchronizing bursts of epileptiform activity known as interictal epileptiform discharges (IEDs) can, even in the absence of overt seizures, cause transient cognitive impairments (TCI) that include problems with perception or short-term memory. While no evidence from single units is available, it has been assumed that IEDs destroy information represented in neuronal networks. Cultured neuronal networks are a model for generic cortical microcircuits, and their spontaneous activity is characterized by the presence of synchronized network bursts (SNBs), which share a number of properties with IEDs, including the high degree of synchronization and their spontaneous occurrence in the absence of an external stimulus. As a model approach to understanding the processes underlying IEDs, optogenetic stimulation and multielectrode array (MEA) recordings of cultured neuronal networks were used to study whether stimulus information represented in these networks survives SNBs. When such networks are optically stimulated they encode and maintain stimulus information for as long as one second. Experiments involved recording the network response to a single stimulus and trials where two different stimuli were presented sequentially, akin to a paired pulse trial. We broke the sequential stimulus trials into encoding, delay and readout phases and found that regardless of which phase the SNB occurs, stimulus-specific information was impaired. SNBs were observed to increase the mean network firing rate, but this did not translate monotonically into increases in network entropy. It was found that the more excitable a network, the more stereotyped its response was during a network burst. These measurements speak to whether SNBs are capable of transmitting information in addition to blocking it. These results are consistent with previous reports and provide baseline predictions concerning the neural mechanisms by which IEDs might cause TCI.

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Stimulus-evoked high frequency oscillations are present in neuronal networks on microelectrode arrays

Cited by 14 publications

References 62 publications

High-frequency voltage oscillations in cultured astrocytes

High-frequency voltage oscillations in cultured astrocytes

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

Stimulus information stored in lasting active and hidden network states is destroyed by network bursts

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