Approximately 2,700 dendritic spines in Golgi-impregnated hippocampal granule cells were quantified via image analysis 24 h after the unilateral induction of long-term potentiation in seven rats. Stereological corrections were made using a tilting disector and analytical unfolding technique. In the potentiated hemisphere the mean spine density along dendrites was reduced by approximately 20%. The relative frequency of shorter, thicker spines was increased in potentiated tissue. Physiological consequences of two morphological changes leading to a reduction in spine density (retraction or fusion of spines) were examined using a compartmental model of a simplified granule cell. The model was constructed in the NEURON modeling environment and included a realistic population of 60 dendritic spines (with dual-component synapses and active Ca(2+)-dependent mechanisms). Simulations demonstrated that potentiation of postsynaptic responses was compatible with fusion (with branching) of a proportion of spines with their neighbors but was not compatible with retraction of spines. This result held over wide variations of model parameters as long as dendritic membranes were assumed to be excitable.