Thalamo-cortical slow wave activity in the sub-delta range determines internal brain states. Such waves occur spontaneously, but may also be evoked by sensory stimulation. They propagate over long distances in the brain. Here we show for the first time that slow-wave-associated Ca2+ transients in vivo behave like global network Ca2+ spikes, invading most of the cortex and thalamus. Like ordinary single cell action potentials, global network Ca2+ spikes are evoked in an all-or-nothing manner, exhibit refractoriness during too frequent repetitive stimulation and propagate over long distances into cortex and thalamus. Global network Ca2+ spikes are generated during UP states by action potential mediated Ca2+ influx into neuronal cell bodies, as well as their axonal and dendritic processes. An optogenetic analysis demonstrated that they can be evoked intracortically by brief stimulation of a local group of virally transduced ChR2-expressing layer 5 cortical neurons. By using paired cortico-cortical, thalamo-cortical and thalamo-thalamical optical fiber Ca2+ recordings as well as a new approach of cortical surface Ca2+ imaging, we found that locally-evoked network Ca2+ spikes initially invade the cortex, followed by a secondary recruitment of the thalamus. The temporal invariance and the globality of the network Ca2+ spikes suggest the presence of unitary time windows of large-scale correlated cortico-thalamic integration of information generated by single sensory modality activation.