Homeostatic plasticity plays a critical role in the stability of neuronal activities. Here, with high-density hippocampal networks cultured on multi-electrode arrays (MEAs), the transformation of spontaneous neuronal firing patterns induced by 1microM tetrodotoxin was clarified. Once tetrodotoxin was washed out after a 4-h treatment, spontaneous activities rose significantly with spike rate increasing approximately three times, and synchronized burst oscillations appeared throughout the network, with the cross-correlation coefficient between the active sites rising from 0.06+/-0.03 to 0.27+/-0.05. The long-term recording showed that the oscillations lasted for more than 4h before the network recovered. These results suggest that short-term treatment by tetrodotoxin may induce the homeostatically enhanced neuronal excitability, and that the spontaneous synchronized oscillations should be an indicator of homeostatic plasticity in cultured neuronal network. Furthermore, the non-invasive and long-term recording with MEAs as a novel sensing system is identified to be appropriate for pharmacological investigations of neuronal plasticity at the network level.