Neocortical neurons maintain high firing rates across all behavioral states of vigilance but the discharge patterns vary during different types of brain oscillations, which are assumed to play an important role in information processing and memory consolidation. In the present study, we report that trains of stimuli applied to local neocortical networks of cats, at frequencies that mimic endogenous brain rhythms, produced depression or potentiation of postsynaptic potentials, which lasted for several minutes. This form of synaptic plasticity was not mediated through NMDA receptors since it persisted after blockade of these receptors, but was strongly modulated by the level of background neuronal activity. Using different preparations in vivo, we found that increased background neuronal activity decreased the probability of plastic changes but enhanced the probability of potentiation over depression. Conversely, when the level of background neuronal activity was low, plasticity was observed in all neurons, but mainly depression was induced. Our results demonstrate that high levels of neuronal activity in the cortical network promote potentiation and insure the stability of synaptic connections.