Tetanic stimulation has long been used to induce plasticity in neuronal networks. However, it was technically difficult to precisely characterize how tetanic stimulation of a single neuron influences the connections to a large number of post-synaptic neurons. In the present study, we addressed this question in dissociated cultured neurons on a high-density CMOS microelectrode array. The CMOS array offers subcellular-resolution recording from 11,011 electrodes within a 2 x 2 mm² area and extracellular microstimulation through arbitrarily selectable electrodes. By measurements of the spontaneous activity, all active cells in the test dishes were localized. A stimulation site was then determined so that the stimulation pulses delivered to an axon reproducibly induced antidromic activation of the respective single neuron. Microstimulation-evoked activity patterns were investigated in terms of conditional firing probability to estimate the connectivity between the directly stimulated neuron and other neurons. Tetanic stimulation was then used to induce plasticity in the neural population. The tetanic stimulation consisted of 20 sets of 10 pulses at 20 Hz with 5-sec intervals. We observed a trend that tetanic stimulation weakened strong connections, while it strengthened weak connections. This tetanic-stimulation-induced plasticity lasted at least for 2 hours, indicating that the synaptic depletion is not the cause. Thus, without activation of post-synaptic neurons, tetanic stimulation of a single neuron induces long-lasting plasticity that may make the post-synaptic connectivity homogeneous.