During development, critical periods of synaptic plasticity facilitate the reordering and refinement of neural connections, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. The L4-L2/3 synapses in the somatosensory cortex (S1) exhibit a presynaptic form of spike timing-dependent long-term depression (t-LTD) that probably fulfills a role in synaptic refinement. This t-LTD persists until the 4rd postnatal week in mice, disappearing thereafter. When we investigated the mechanisms underlying this maturation-related loss of t-LTD in mouse slices, we found that it could be completely recovered by antagonizing adenosine type 1 receptors (A1R). By contrast, an agonist of A1R impeded the induction of t-LTD at P13-27. Furthermore, we found that the adenosine that mediated the loss of t-LTD supplied by astrocytes. At more mature stages (P38-60), we found that the protocol used to induce t-LTD provokes t-LTP. We characterized this LTP and found it to be expressed presynaptically, as witnessed by paired-pulse and coefficient of variation analysis. In addition, it requires the activation of NMDARs and mGlu1Rs, and the entry of Ca2+ into the postsynaptic neuron through L-type voltage-dependent Ca2+ channels. Nitric oxide is also required for t-LTP as a messenger in the postsynaptic neuron, as are the adenosine and glutamate that are released in association with astrocyte signaling. These results provide direct evidence of the mechanisms that close the window of plasticity associated with t-LTD and that drive the switch in synaptic transmission from t-LTD to t-LTP at L4-L2/3 synapses, in which astrocytes play a central role