Fig. 6 | Nature Communications

Fig. 6

From: Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity

Fig. 6

GluN2C/D-containing NMDARs contribute to NMDAR EPSCs but not GNE-8324 potentiation in inhibitory neurons. a NAB-14 reduces NMDAR EPSC areas in inhibitory but not excitatory neurons. b Sensitivity to GNE-8324. Left: Current trace examples of GNE-8324 dose–response recordings from oocytes expressing either diheteromeric GluN1/GluN2A or GluN1/GluN2D* NMDARs, or triheteromeric GluN1/GluN2A/GluN2D* NMDARs. Scale bars, 200 nA/50 s (top), 20 nA/50 s (middle), and 10 nA/50 s (bottom). Right: GNE-8324 dose–response curves for GluN1/GluN2A, GluN1/GluN2D*, or GluN1/GluN2A/GluN2D* NMDARs. N = 5–7 oocytes/concentration. c Sensitivity to NAB-14. Effect of 1 and 10 µM NAB-14 on diheteromeric GluN1/GluN2A NMDARs, diheteromeric GluN1/GluN2D* NMDARs, and triheteromeric GluN1/GluN2A/GluN2D* NMDARs. Later, 20 µM NAB-14 was also tested. Right: Illustrative current trace showing inhibition of triheteromeric GluN1/GluN2A/GluN2D* NMDAR activity by 20 µM NAB-14. Scale bars, 20 nA/40 s. N = 3–7 oocytes/concentration. **P < 0.01, ***P < 0.001, one-way ANOVA with Tukey's correction. d NAB-14 does not affect the level of GNE-8324 potentiation on NMDAR EPSCs in inhibitory neurons. Left: Sample traces showing similar potentiation of NMDAR EPSCs by GNE-8324 in NAB-14-treated slice and Veh-treated slice. Scale bars, 50 pA/100 ms. N = 7, 6, 8, for Veh + 8324, NAB-14 + 8324, and NAB-14 + Veh, respectively. *P < 0.05, one-way ANOVA with Dunnett's correction. Right: Population data. Error bars represent SEM

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