Neurons are capable of changing their functional properties and morphology throughout the life of animals, a phenomenon called plasticity. An important question is how do the functional and structural changes relate to one another. Very few studies, however, have directly examined which neuronal pathways are activated during experimental manipulations that induce functional plasticity and what are the patterns of synaptic activation necessary to induce structural changes. Here, we hypothesized that the coincident activation of two thalamocortical pathways can lead to both functional and structural plasticity. Using the somatosensory whisker-related system of the mouse as a model, we find that paired stimulation of these two pathways leads to potentiation of subthreshold whisker-evoked responses. Paired stimulation also leads to overall spine shrinkage that is most prevalent in the population of superficial spines, coinciding with a convergence zone of the two pathways, indicating that heterosynaptic shrinkage may be a mechanism involved.