Although synaptic plasticity is a widespread phenomenon, the underlying mechanisms leading to its occurrence are virtually unknown. In this sense, glial cells, especially astrocytes, may have a role in network changes of the nervous system, influencing the retraction of boutons as well as providing a proper perisynaptic environment, thereby affecting the replacement of inputs. Interestingly, the glial reaction does vary between strains of rats and mice. In this sense, we present evidence that C57BL/6J and A/J isogenic mice present different astrocyte reactivity after a peripheral lesion in vivo as well as in vitro, by analyzing primary cell cultures. Such a difference in the glial reaction has a direct influence on in vivo number of pre-synaptic terminals and on in vitro synaptogenesis.