Chronically elevating spontaneous activity in cultured neuronal networks results in distint homeostatic changes
Law, Rachel Candace
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During the first few weeks in vitro, cultured neuronal networks exhibit spontaneous bursts of action potentials, even in the absence of external input . Pharmacological intervention, as well as electrical stimulation provide a direct means for chronically elevating this spontaneous network activity and allow the study of homeostatic plasticity [3, 8]. In this study, embryonic day 18 rat cortical neurons were dissociated and grown on multi-electrode arrays (MEAs). During the third week in vitro, activity was chronically increased for 24 hours by disinhibiting the network using a GABA_A receptor antagonist, or by electrically stimulating the network using the MEA. Spiking activity was continuously recorded through the MEA before, during, and after each perturbation, and the frequency of spontaneous population bursts was obtained to give insight on how the overall network was affected. Chronic pharmacological blockade of GABA_A receptors increased culture burst frequency and after washing out the drug, a significant homeostatic reduction in bursting was observed. Meanwhile, the same increase in elevated burst frequency was attempted using distributed electrical stimulation. Although electrical stimulation did not increase activity in every trial, of the cultures that did experience elevated bursting, a surprisingly distinct homeostatic effect was seen. When compared to drug treated cultures that had similar increases in burst frequency, there was a significant difference in bursting immediately following treatment ending. These experiments may help improve our knowledge of clinical interventions where neural tissue is subject to chronic electrical stimulation, as well as identify the consequences of these therapeutic approaches.