Facilitated NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 area of dystrophin-deficient mice

The contribution of the cytoskeletal membrane-associated protein dystrophin in glutamatergic transmission and related plasticity was investigated in the hippocampal CA1 area of wild-type and dystrophin-deficient (mdx) mice, using extracellular recordings in the ex vivo slice preparation. Presynaptic fiber volleys and field excitatory postsynaptic potentials (fEPSPs) mediated through N-methyl-D-Aspartate receptors (NMDAr) or non-NMDAr were compared in both strains. Comparable synaptic responses were observed in wild-type and mdx mice, suggesting that basal glutamatergic transmission is not altered in the mutants. By contrast, the synaptic strengthening induced by a conditioning stimulation of either 10, 30, or 100 Hz was significantly greater in mdx mice during the first minutes posttetanus. Because the posttetanic potentiation induced in the presence of the NMDAr antagonist D-APV was not affected in the mutants, a critical role of NMDAr in this increase was suggested. The magnitude of the potentiation induced by a 30 Hz stimulation in mdx mice was normalized as compared to wild-type mice by increasing the extracellular magnesium concentration from 1.5 to 3 mM. Moreover, the transitory depression of fEPSPs induced by bath-applied NMDA (50 microM for 30s) was more sensitive to an increased extracellular magnesium concentration in wild-type than in mdx mice. Our results suggest that the absence of dystrophin may facilitate NMDAr activation in the CA1 hippocampal subfield of mdx mice, which may be partly due to a reduction of the voltage-dependent block of this receptor by magnesium.