The two processes of activation in thalamocortical systems exerted by mesopontine cholinergic neurons are (a) a direct depolarization associated with increased input resistance of thalamic relay neurons, which is antagonized by muscarinic blockers, and (b) a disinhibition of the same neurons via hyperpolarization of inhibitory thalamic reticular neurons. Low-frequency (< 15 Hz) oscillations during slow-wave sleep, characterized by rhythmic and prolonged hyperpolarizations, are suppressed by brainstem cholinergic neurons and nucleus basalis cholinergic and GABAergic neurons projecting to thalamic reticular neurons. Fast rhythms (20-60 Hz) appear during the sustained depolarization of thalamic and neocortical neurons during brain-active states that are accompanied by increased release of acetylcholine (ACh) in the thalamus and cerebral cortex. Such fast rhythms also occur during the depolarizing phases of the slow oscillation (0.5-1 Hz) in non-REM sleep. Intracellular recordings of neocortical neurons during natural states of waking and sleep demonstrate stable and increased input resistance of corticocortical and corticothalamic neurons during the sustained depolarization in wakefulness, compared to the depolarizing phase of the slow oscillation in non-REM sleep. Despite the highly increased synaptic inputs along different afferent systems that open many conductances of cortical neurons during wakefulness, the increased input resistance is attributed to the effect of acetylcholine on cortical neurons.