The origin of rhythm generation in mammalian spinal cord networks is still poorly understood. We have previously proposed that disinhibition-induced rhythms are based on intrinsic firing, recurrent excitation and several mechanisms to de-activate the network. In order to clarify these mechanisms we here investigated spontaneous spike discharge oscillations in rat spinal cord slice cultures using multi-electrode arrays and patch clamp. Episodes of such oscillations at 8.5 Hz spontaneously appeared in the ventral parts of the cultured slices. The rising phase of their initial cycles was entirely based on AMPA/kainate receptor-dependent recurrent excitation. Initial oscillations were changed into persistent activity by bicuculline and other blockers of GABA A, but not by blockers of glycine receptors, suggesting a role for GABAergic synaptic inhibition in network de-activation during oscillation cycles. Blockade of glycine receptors by strychnine caused a prolongation of oscillations and their spreading in the slice, suggesting that these receptors are mainly involved in the spatial and temporal restriction of oscillations. In most cultures, oscillations reappeared under disinhibition after an initial phase of persistent activity. Both spontaneous and disinhibition-induced oscillations were facilitated by riluzole, which enhances fast sodium current inactivation and thus leads to early cessation of firing during strong depolarization (depolarization block). In single cell recordings, episodes of strong depolarization were mostly seen during oscillations induced by disinhibition, but occasionally also during spontaneous oscillations. We conclude that both GABA A-mediated synaptic inhibition and depolarization block contribute to the de-activation of spinal cord networks during oscillation cycles.