Chronic stimulation of cultured neuronal networks boosts low-frequency oscillatory activity at theta and gamma with spikes phase-locked to gamma frequencies.

Slow wave oscillations in the brain are essential for coordinated network activity but have not been shown to self-organize in vitro. Here, the development of dissociated hippocampal neurons into an active network with oscillations on multi-electrode arrays was evaluated in the absence and presence of chronic external stimulation. Significant changes in signal power were observed in the range of 1-400 Hz with an increase in amplitude during bursts. Stimulation increased oscillatory activity primarily in the theta (4-11 Hz) and slow gamma (30-55 Hz) bands. Spikes were most prominently phase-locked to the slow gamma waves. Notably, the dissociated network self-organized to exhibit sustained delta, theta, beta and gamma oscillations without input from cortex, thalamus or organized pyramidal cell layers.