NMDAR2 upregulation precedes mossy fiber sprouting in kainate rat hippocampal epilepsy

Following intrahippocampal (hilar) kainic acid (KA) lesions in rats, NMDAR2A/B receptor proteins are upregulated significantly in the inner molecular layer (IML) of the dentate gyrus by post-injection day 5. By contrast, the aberrant mossy fibers which reinnervate the IML remained in the subgranular zone before sprouting and synapsing in the IML, which occurs at approximately post-KA day 17. For 40 days thereafter, this mossy fiber ingrowth progressed, while the increased NMDAR2A/B (receptors) immunoreactivity remained at the same densities. These results suggest that new NMDAR2A/B proteins in granule cell dendrites are limited to the IML, which is the eventual site for MF hyperinnervation, neosynaptogenesis, and recurrent synaptic hyperexcitability.