Mn2+ -enhanced magnetic resonance imaging (MEMRI) was used to characterize activity-dependent plasticity in the moss), fiber pathway after intraperitoneal kainic acid (KA) injection. Enhancement of the MEMRI signal in the dentate gyrus and the CA3 subregion of the hippocampus was evident 3 to 5 days after injection of MnCl2 into the entorhinal cortex both in control and KA-injected rats. In volume-rendered three-dimensional reconstructions, Mn2+-induced signal enhancement revealed the extent of the mossy fiber pathway throughout the septotemporal axis of the dentate gyrus. An increase in the number of Mn2+ -enhanced pixels in the dentate gyrus and CA3 subfield of rats with KA injection correlated (P <0.05) with histologically verified mossy fiber sprouting. These data demonstrate that MEMRI can be used to detect specific changes at the cellular level during activity-dependent plasticity in vivo. The present findings also suggest that MEMRI signal changes can serve as an imaging marker of epileptogenesis. (c) 2005 Elsevier Inc. All rights reserved.