Brain-derived neurotrophic factor (BDNF) has been reported to exert an acute potentiation of synaptic activity. Here we examined the action of BDNF on synchronous spontaneous Ca(2+) oscillations in cultured cerebral cortical neurons prepared from postnatal 2-3-day-old rats. The synchronous spontaneous Ca(2+) oscillations began at approximately DIV 5. It was revealed that voltage-dependent Ca(2+) channels and ionotropic glutamate receptors were involved in the synchronous spontaneous oscillatory activity. BDNF potentiated the frequency of these oscillations. The BDNF-potentiated activity reached 207 +/- 20.1% of basal oscillatory activity. NT-3 and NT-4/5 also induced the potentiation. However, nerve growth factor did not. We examined the correlation between BDNF-induced glutamate release and the BDNF-potentiated oscillatory activity. Both up-regulation of phospholipase C-gamma (PLC-gamma) expression and the BDNF-induced glutamate release occurred at approximately DIV 5 when the BDNF-potentiated oscillations appeared. We confirmed that the BDNF-induced glutamate release occurred through a glutamate transporter that was dependent on the PLC-gamma/IP(3)/Ca(2+) pathway. Transporter inhibitors blocked the BDNF-potentiated oscillations, demonstrating that BDNF enhanced the glutamatergic transmissions in the developing cortical network by inducing glutamate release via a glutamate transporter.