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T Ladewig, S Fellner, E Guenther; BDNF Regulation of NMDA Receptor Function in the Rat Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2703.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Growth factors have been implicated in the regulation of neuronal survival and differentiation during development. However in recent years the idea of neurotrophic factors modulating synaptic transmission has gained increasing interest (Sherwood & Lo, 1999). In order to assess the effect of brain-derived neurotrophic factor (BDNF) on glutamate receptors of the NMDA type, reported to be involved in synaptic transmission and plasticity, we have performed patch-clamp recordings on retinal gangion cells in wildtype and BDNF knockout mice. Methods: BDNF -/- mutants were obtained by cross breeding heterozygous mice from a well characterized line of BDNF null-mutant mice (Korte et al., 1995). The animals were genotyped by performing PCR on genomic DNA. Retinas from wildtype, BDNF +/- and -/- mice were examined at postnatal days P3 to P12. Electrophysiological responses to the externally applied glutamate agonist NMDA (in concentrations from 500 µM up to 2 mM) of ganglion cells in a retinal slice preparation were recorded using the whole-cell patch-clamp technique, while AMPA and GABA receptor activity were blocked by the selective antagonists CNQX and bicuculline, respectively. Results: We found that peak amplitudes of NMDA-evoked currents in -/- mutant retinal ganglion cells at postnatal days P3 - P12 in vitro were significantly decreased compared to that of wildtype mice at the same age. Heterozygous mutant mice showed an intermediate reduction of NMDA responses. A restoration of the decreased NMDA receptor activity by a 1 to 3 hour incubation of -/- mice retinal slices in BDNF (100 ng/ml) was not observed. Conclusion: BDNF seems to be responsible for the expression of functional NMDA channels in retinal ganglion cells. Our results suggest that BDNF has long-term (days to weeks) but not short-term (minutes to hours) effects on excitatory synaptic transmission in retinal ganglion cells. The mechanism of BDNF regulation of NMDA receptor activity remains to be determined. Supported by Grimmke-Foundation and German Research Council (SFB 430).
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