The brain is continuously active. Spontaneous neuronal activity is prevalent in vivo and in vitro and could reflect intrinsic functional properties of the microcircuit, so its dynamics may help reveal the basic logic of network operations. However, it is largely unknown how such naturally generated spikes are organized or how they can affect individual synaptic efficacy. We reconstructed spike patterns of many cortical neurons in vitro and found that sequences of activity were reactivated in the same spatiotemporal order. Spontaneous activity drifts with time, recruiting different sets of cells, and thereby, sequences are replaced with novel patterns. Patterns of spontaneous activity were predictable by training a feedback neural network model with a past period of dataset. We also sought to determine whether spontaneous activity alters synaptic strength. When hippocampal slices were exposed to ACSF that mimicked the extracellular ionic compositions in vivo, cells started to exhibit slow wave oscillations with rhythmic action potentials. After wash-out, postsynaptic currents were altered at CA3 synapses. The direction of synaptic plasticity was determined by the frequency of UP-DOWN state alternations. When the modified ACSF was repetitively applied, identical cells generated different oscillation rhythms, and thus, changes in synaptic efficacy varied from trial to trial. Therefore, spontaneous self-excitation of cortical networks is non-randomly structured and can modify synaptic weights. Our talk provides a novel regimen of cortical operations, i.e., self-rewritable microcircuitry with ongoing plasticity. [J Physiol Sci. 2006;56 Suppl:S14]