We characterize sleep-like states in cultured neurons and glia during development in vitro, and after electrical stimulation, the addition of tumor necrosis factor alpha (TNF), and the combination of TNF plus electrical stimulation. We also characterize optogenetic stimulation-induced ATP release and neuronal interleukin-1 and TNF expression in vitro demonstrating the activity-dependence of these putative sleep regulatory substances. Action potential (AP) burstiness (BI; burstiness index), synchronization of slow electrical potentials between recording electrodes (SYN), and slow wave (SW) power (0.25 - 3.75Hz) determined using fast Fourier analyses emerged as network properties, maturing after two weeks in culture. Homologous in vivo measures are used to characterize sleep. Electrical stimulation reduced the BI, SYN, and SW power values during and/or after the stimulus period. One day later, homeostasis was evident by rebounds of SYN and SW power values to above baseline levels; the magnitude of the rebound was stimulus pattern-dependent. The addition of TNF enhanced BI, SYN, and SW power values suggesting the induction of a deeper sleep-like state. Electrical stimulation reversed these TNF effects suggesting the network state was more wake-like. The day after TNF plus electrical stimulation, the changes in SYN and SW power values were dependent upon the stimulus patterns the cells received the day before. We conclude that sleep- and wake states in cultured in vitro networks can be controlled and they share molecular regulatory mechanisms with local in vivo networks. Further, sleep is an activity-dependent emergent local network property. This article is protected by copyright. All rights reserved.
This research output has an Altmetric Attention Score of 42. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 November 2017.
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