Tumor necrosis factor alters evoked response potentials in dissociated neural networks in culture

Abstract

Neural circuits such as cortical columns individually oscillate between functional states which are correlative with whole-organism sleep and waking. Localized injections of cytokines such as tumor necrosis factor alpha (TNF) alter the functional state oscillations, pointing to their role in regulating local sleep. In this study, alteration of functional states by TNF, as evidenced by changed electrical response properties, was demonstrated in dissociated neural networks grown in tissue culture. Specifically, mixed cultures of neurons and glia from 1-day-old mice were grown on multi-electrode-array (MEA) dishes. The cultures were subjected to 1 Hz electrical stimulation at a single electrode over 30 minutes, just after addition of 0.1 ng TNF to the culture bath. Data were bandpass-filtered between 0.1 and 200 Hz to extract slow-wave response characteristics. Evoked response potentials (ERPs), i.e. slow-wave depolarizations induced by a single stimulus, were compared. ERPs after TNF addition exhibit (1) larger response amplitudes, (2) increased signal consistency (decreased variability) over time and across channels, and (3) enhanced cross-channel correlation, compared to the baseline. These patterns match with ERP characteristics observed in vivo during sleep and wake. TNF addition enhances the sleep-like state, in correspondence with its role as a sleep promoter.