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Xenon pressure dependence on the synchronized burst inhibition of rat cortical neuronal network cultured on multi-electrode arrays.

ABSTRACT: Mature rat cortical neuronal networks cultured on multi-electrode arrays (MEAs) are known to show spontaneous synchronized bursts accompanied by independent single spikes. The spontaneous synchronized bursts can be inhibited by Xe gas. In this study, we adjust the Xe gas pressure to control the amount of Xe in a neuron-cultured MEA medium. We show that the synchronized bursts cease completely within several minutes by applying Xe gas at partial pressures above 0.3 MPa. After depressurizing and purging with fresh air, the synchronized bursts recover to their original frequency. Thus, we confirmed that Xe acts as a network-activity inhibitor of the cultured neuronal network on MEAs. But below 0.3 MPa, the synchronized bursts are inhibited only partially, depending on the Xe partial pressure. Based on the partial-pressure influence on the change of the neuronal network activities, we find the critical concentration of Xe for the inhibition effect to be approximately 9.5 mM, a value above which more than 90% of the synchronized burst activity is inhibited. Further systematic observations with Xe-air mixed gases show that pressurized air with a small amount of Xe suppresses the inhibition of synchronized bursts, suggesting an air component that can accelerate the synchronized bursts.

SUBMITTER: Uchida T

PROVIDER: S-EPMC6084913 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat ('artificial animal') applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown.ResultsConsequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion.ConclusionsWe suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

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Xenon pressure dependence on the synchronized burst inhibition of rat cortical neuronal network cultured on multi-electrode arrays.

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