Plasticity of the cerebral cortex following a modification of the sensorimotor experience takes place in several steps that can last from few hours to several months. Among the mechanisms involved in the dynamic modulation of the cerebral cortex in adults, it is commonly proposed that short-term plasticity reflects changes in synaptic connections. Here, we were interested in the time-course of synaptic plasticity taking place in the somatosensory primary cortex all along a 14-day period of sensorimotor perturbation (SMP), as well as during a recovery phase up to 24 h. Activation and expression level of pre- (synapsin 1, synaptophysin, synaptotagmin 1) and postsynaptic (AMPA and NMDA receptors) proteins, postsynaptic density scaffold proteins (PSD-95 and Shank2), and cytoskeletal proteins (neurofilaments-L and M, β3-tubulin, synaptopodin, N-cadherin) were determined in cortical tissue enriched in synaptic proteins. During the SMP period, most changes were observed as soon as D7 in the presynaptic compartment and were followed, at D14, by changes in the postsynaptic compartment. These changes persisted at least until 24 h of recovery. Proteins involved in synapse structure (scaffolding, adhesion, cytoskeletal) were mildly affected and almost exclusively at D14. We concluded that experience-dependent reorganization of somatotopic cortical maps is accompanied by changes in synaptic transmission with a very close time-course.