Oscillatory patterns in neocortical electrical activity show various degrees of large-scale synchrony depending on experimental conditions, but the exact mechanisms underlying these variations of coherence are not known. Analysis of multisite local field potentials revealed that the coherence of spindle oscillations varied during different states. During natural sleep, the coherence was remarkably high over cortical distances of several millimeters, but could be disrupted by artificial cortical depression, similar to the effect of barbiturates. Possible mechanisms for these variations of coherence were investigated by computational models of interacting cortical and thalamic neurons, including their intrinsic firing patterns and various synaptic receptors present in the circuitry. The model indicates that modulation of the excitability of the cortex can affect spatiotemporal coherence with no change in the thalamus. The highest level of coherence was obtained by enhancing the excitability of cortical pyramidal cells, simulating the action of neuromodulators such as acetylcholine and noradrenaline. The underlying mechanism was due to cortex-thalamus-cortex loops in which a more excitable cortical network generated a more powerful and coherent feedback onto the thalamus, resulting in highly coherent oscillations, similar to the properties measured during natural sleep. In conclusion, these experiments and models are compatible with a powerful role for the cortex in triggering and synchronizing oscillations generated in the thalamus, through corticothalamic feedback projections. The model suggests that intracortical mechanisms may be responsible for synchronizing oscillations over cortical distances of several millimeters through cortex-thalamus-cortex loops, thus providing a possible cellular mechanism to explain the genesis of large-scale coherent oscillations in the thalamocortical system.