The oscillatory rhythms underlying many physiological and pathological states, including absence seizures, require both the thalamus and cortices for full expression. A co-culture preparation combining cortical and thalamic explants provides a unique model for investigating how such oscillations initiate and spread. Here we investigated the dynamics of synchronized thalamocortical activity by simultaneous measurement of field-potential recordings and rapid imaging of Ca(2+) transients by fluorescence methods. Spontaneous sustained hypersynchronized "seizure-like" oscillations required reciprocal cortico-thalamocortical connections. Isolated cortical explants can independently develop brief discharges, while thalamic explants alone were unable to do so. Rapid imaging of Ca(2+) transients demonstrated deep-layer cortical initiation of oscillatory network activity in both connected and isolated explants. Further, cortical explants derived from a rat model of genetic absence epilepsy showed increased bursting duration consistent with an excitable cortex. We propose that thalamocortical oscillatory network activity initiates in deep layers of the cortex with reciprocal thalamic interconnections enabling sustained hyper-synchronization.