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Network analysis of hippocampal neurons by microelectrode array in the presence of HIV‐1 Tat and cocaine

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Journal of Cellular Physiology

Published online on

Abstract

--- - |2+ HIV‐associated neurocognitive disorders affecting greater than 30% of patients are caused by HIV‐1 infection of the CNS, and in part, include neurotoxic effects of the viral transactivator of transcription, Tat protein. In addition to increasing the risk for becoming HIV infected, cocaine abuse enhances the neuropathogenic impacts of HIV‐1. To investigate the outcome of Tat and cocaine interference in the hippocampal neuronal network, cross‐rank‐corrlation was employed to develop a systematic framework to assess hippocampal neurons behavior cultured on multielectrode arrays. Tat and cocaine differentially disturbed neuronal spiking rates, amplitude, synchronous activity, and oscillations within the hippocampal neuronal network via potentiation of inhibitory neurotransmission. The Tat‐mediated impairment of neuronal spiking was reversible by removal of Tat, which restored neuronal activity. The presence of astrocytes co‐cultured with neuronal networks diminished the effects of Tat and cocaine on neuron function suggesting a role for astrocytes in stabilizing neuronal behavior and increasing neuronal spontaneous activities such as bursting amplitude, frequency, and wave propagation rate. Taken together, our studies indicate that the HIV protein Tat and cocaine impair hippocampal neuronal network functioning and that the presence of astrocytes alleviates network dysfunction pointing to a newly discovered pathway through which ionic homeostasis is maintained by neuron‐glial crosstalk in the CNS. - Journal of Cellular Physiology, Volume 233, Issue 12, Page 9299-9311, December 2018.