NMDAR1 receptor proteins and mossy fibers in the fascia dentata during ratkainate hippocampal epileptogenesis

We examined the time course of NMDAR1 (NR1) immunoreactivity (IR) in the ra t inner molecular layer of the dentate gyrus following unilateral intrahipp ocampal (hilar) kainic acid (KA) lesions and compared them to progressive a berrant mossy fiber (MF) sprouting into the inner molecular layer (IML). Th e results demonstrated that NR1 receptors in the IML of the KA side were de creased as early as 3 days after KA-induced denervation, then significantly increased at postinjection day (PID) 7. The densities of NR1 IR in the IML continued to increase up to 5 months. By comparison, RIF sprouting did not occur significantly in the IML until PID 17, 10 days after NR1 IR was sign ificantly increased. Recurrent MF-IML neoinnervation significantly increase d on days 17, 60, and 150. This progressive MF innervation was significantl y correlated with NR1 increases. These results suggest that NR1 receptors w ere decreased soon after KA-induced deafferentation of granule cell dendrit es in the IML; however, they were replaced by new NR1 receptors at increase d densities in the granule cell dendrites, which may have released neurotro phic factors to stimulate growth cones of MFs to reinnervate the IML. The p rogressive increases of NR1 and MFs in the IML suggest that such neosynapto genesis would contribute monosynaptic recurrent excitatory mechanisms for f ocal hippocampal hyperexcitability and seizure onsets. (C) 2000 Academic Pr ess.