Research Paper Volume 11, Issue 14 pp 5140—5157

Subunit contribution to NMDA receptor hypofunction and redox sensitivity of hippocampal synaptic transmission during aging

Figure 3. Input-output curves examining age-related differences in the peak NMDAR EPSCs under control conditions and in the presence of DTT (0.5 mM). The cells were voltage clamped at +40 mV. (A) Bath application of DTT (filled circle, n = 8/2 cells/animals) failed to increase NMDAR EPSCs for CA1 pyramidal cells recorded from young animals relative to the control condition (open circle, n = 25/11 cells/animals). (B) Across the range of stimulation intensities, DTT (filled circle, n = 7/3 cells/animals) significantly augmented NMDAR EPSCs in CA1 cells recorded from aged animals relative to the control condition (open circle, n = 26/14 cells/animals). (C) DTT increases the time to half-decay of the NMDAR synaptic response. The symbols represent the mean (±SEM) time of NMDAR-mediated EPSC to decay to 50% of the peak under control conditions and in the presence of DTT for the three highest stimulation intensities. The inset (left) shows time course of the EPSC, evoked by 40 V stimulation, across all CA1 pyramidal cells recorded from young animals under the control condition (gray trace, n = 20/9 cells/animals) and in the presence of DTT (black trace, n = 8/2 cells/animals). The inset (right) time course of the EPSC, evoked by 40 V stimulation, across all CA1 pyramidal cells recorded from aged animals under the control condition (gray trace, n = 26/14 cells/animals) and in the presence of DTT (black trace, n = 7/3 cells/animals). For each cell, the response amplitude evoked by 40 V stimulation was normalized to the peak of the response. (D) Increased contribution of the GluN2B subunit to the peak NMDAR EPSC following DTT-induced potentiation of NMDAR EPSCs in slices obtained from aged animals. The cells were voltage clamped at +40 mV and input-output curves of the peak NMDAR EPSCs were generated in presence of DTT (open circle, n = 7/3 cells/animals), DTT+NVP (gray circle, n = 5/2 cells/animals), and DTT+ifenprodil (filled circle, n = 5/3 cells/animals).