Abstract
Abstract: :
Purpose: Changes in N-methyl-D-aspartate receptor (NMDAR) properties are reported to regulate periods of plasticity in different cortical areas. In order to learn whether similar changes occur in the retina, structure-function relationships of NMDAR were investigated in rat retinal ganglion cells (RGCs) during retinal development. Methods: Perforated-patch clamp recordings of NMDAR-currents were carried out on identified retinal ganglion cells in a slice preparation of the pigmented rat retina, followed by single-cell RT PCR and semi-quantitative dot blots to analyze the NMDAR subunit distribution in individual RGCs. Drugs were applied by a fast superfusion system via a pipette located in a distance of about 100 µm from the RGC recorded. Results: Before eye opening, all RGCs investigated between postnatal day (P) 9-12 had large NMDAR currents with mean amplitudes of -110 pA (±53 pA SD). When animals were kept in a 12 h light-dark cycle, NMDAR current amplitudes decreased after eye opening to a mean value of -13 pA (±7 pA SD) at P30 and could be elicited in only 65% of the RGCs. In contrast, dark rearing animals, up to P30, prevented this decrease of NMDAR currents. In dark-reared animals, NMDAR currents could be recorded in 93% of RGCs with mean amplitudes of -81 pA (±25 pA SD). Subsequent light exposure for as little as 5 days induced a down regulation of NMDAR current amplitude to a mean of -19 pA (±7 pA SD). Single-cell RT PCR analysis revealed distinct developmental alterations in the composition of NMDAR subunits in RGCs; however, none of them were induced by the onset of light. Conclusion: Our data indicate that the light-induced decrease of NMDAR currents in rat retinal ganglion cells is not caused by alterations in the molecular structure of NMDA receptors. This is in contrast to cortical neurons where alterations in NMDAR properties during development seem to be related to an increased substitution of subunit NR2A for NR2B in the NMDA channel complex. Since the down-regulation of NMDAR in RGCs occurs after eye opening, when the retinal network is reported to be mature, we hypothetise that NMDAR function in RGCs is related to periods of retinal plasticity and is regulated by a post-translational mechanisms acting on the NMDAR protein rather than a change in NMDAR subunit expression and composition.
Keywords: 401 excitatory amino acid receptors • 415 ganglion cells • 520 plasticity