Glutamate receptor block in Lurcher mutant mice during ontogeny and its effect on hippocampal long-term potentiation

Basic evaluation of the effect of chronic NMDA glutamate receptor (NMDAR) blockade on the hippocampal long-term potentiation (LTP) was performed in an animal model of inborn olivo-cerebellar degeneration (Lurcher mutant mice, LMM). NMDA receptor antagonist MK-801 was administered to mice in the dose 0.2 mg/kg of body weight, daily during two periods of their ontogeny: D5-D26 and D91-D111. In the consecutive 15 days some behavioral characteristics were studied using special methods for physical activity testing. Then LTP was investigated in LMM and also in their healthy littermates which served as controls (wild-type, WT). LTP in animals pre-treated with MK-801 showed significant long-term suppression of NMDAR activity, in both WT and LMM despite certain small differences between them. Our results show that cerebellar pathology on one hand and a physical activity on the other hand can influence the LTP in hippocampal region. It can be concluded that the results support the ideas of close functional cooperation between the brain structures which are involved in mechanisms of learning and memory.