Neurons can engage in synchronized oscillatory activity in the gamma-frequency range when responding to sensory stimuli. Both the oscillatory patterning and the synchronization of responses are enhanced with arousal and attention or when the electroencephalogram is activated by electrical stimulation of the mesencephalic reticular formation. Here we show with intracortical application of cholinergic antagonists that the enhancement of gamma oscillations and response synchronization is mediated by acetylcholine and muscarinic receptors. We demonstrate further that coapplication of cholinergic agonists with synchrony-inducing light stimuli causes a lasting increase in the probability that the stimulated cells engage in gamma oscillations and response synchronization. These changes develop slowly over tens of minutes and then persist for many hours. Thus, cholinergic modulation plays a crucial role both in the fast, state-dependent facilitation of gamma oscillations and response synchronization and in use-dependent long-term modifications of cortical dynamics that favor synchronization of responses in the gamma-frequency range.