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 t he hippocampal CA1 area of wild-type and dystrophin-deficient (mdx) mice, u sing extracellular recordings in the ex vivo slice preparation. Presynaptic fiber volleys and field excitatory postsynaptic potentials (fEPSPs) mediat ed through N-methyl-D-Aspartate receptors (NMDAr) or non-NMDAr were compare d in both strains. Comparable synaptic responses were observed in wild-type and mdx mice, suggesting that basal glutamatergic transmission is not alte red in the mutants. By contrast, the synaptic strengthening induced by a co nditioning stimulation of either 10, 30, or 100 Hz was significantly greate r 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 sug gested. 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 ex tracellular magnesium concentration from 1.5 to 3 mM. Moreover, the transit ory depression of fEPSPs induced by bath-applied NMDA (50 mu M for 30s) was more sensitive to an increased extracellular magnesium concentration in wi ld-type than in mdx mice. Our results suggest that the absence of dystrophi n may facilitate NMDAr activation in the CA1 hippocampal subfield of mdx mi ce, which may be partly due to a reduction of the voltage-dependent block o f this receptor by magnesium. Synapse 31:59-70, 1999. (C) 1999 Wiley-Liss, Inc.