Cortical synapses are modified by sensory experience, a process that is considered as a fundamental mechanism to support learning and long-term adaptation to an altered environment. This process occurs developmentally during a window of heightened plasticity called a critical period, but also takes place throughout life. However, the underlying molecular mechanisms remain unclear, especially in mature animals. Here we investigated the mechanism underlying whisker deprivation-induced synaptic weakening after the critical period. Whisker deprivation decreased the presynaptic glutamate release probability at layer 4 (L4)-layer 2/3 (L2/3) synapses in the barrel cortex of mice. As previously reported, type 1 cannabinoid receptor (CB1R)-dependent depression contributes to this weakening during the critical period, in which L2/3 synapses share around postnatal day 12-14. After this period, the involvement of CB1R was diminished and we surprisingly found that deprivation-induced weakening was restored by a positive allosteric modulator of the metabotropic glutamate receptor (mGluR). Furthermore, mGluR antagonists or chronic suppression of inositol 1,4,5-trisphosphate (IP₃) signaling in the L2/3 postsynaptic neurons showed effects similar to those of whisker deprivation. These results suggest that experience-dependent mGluR-IP₃ signaling in the postsynaptic neurons retrogradely regulates the presynaptic functions in the mature barrel cortex, providing a novel insight into deprivation-induced plasticity in the cerebral cortex.