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. 2021 Jun 1;10:e66612. doi: 10.7554/eLife.66612

Figure 3. Reduced facilitation by NMDAR antagonism is independent of the GC somatodendritic compartment.

(A) KAR-EPSCs were recorded at Vh = −70 mV in the presence of 15 µM LY303070 and 100 µM picrotoxin. In addition, NMDAR-mediated transmission was blocked intracellularly by loading MK-801 (2 mM) in the patch-pipette. LFF of KAR-EPSCs was assessed as in Figure 1G but with transected mf axons (see Materials and methods). Bath application of MK-801 (50 µM) significantly reduced LFF (baseline 213 ± 9%, MK-801 181 ± 10%, n = 8 cells, seven animals; baseline vs MK-801, p=0.002, paired t-test). In all panels of this figure: recording arrangement (inset), representative traces (top), representative experiment (middle), normalized LFF and summary plot (bottom). (B) Stable LFF in transected, naïve slices (baseline 186 ± 10%, naïve 196 ± 5%, n = 8 cells, seven animals; baseline vs naïve, p=0.278, paired t-test). (C) LFF was induced before and during puff application of D-APV (2 mM) in stratum lucidum. This manipulation significantly reduced facilitation (baseline 220 ± 19%, D-APV puff 176 ± 11%, n = 7 cells, seven animals; baseline vs D-APV puff, p=0.003, paired t-test). (D) Stable LFF in acute slices during puff application of ACSF (baseline 210% ± 12, naïve 213% ± 9, n = 7 cells, seven animals; baseline vs naïve, p=0.778, paired t-test). NBQX (10 µM) was applied at the end of all recordings to confirm mf KAR transmission. Data are presented as mean ± s.e.m. ***p<0.005.

Figure 3.

Figure 3—figure supplement 1. Targeting preNMDARs located in mf axons, but not granule cells.

Figure 3—figure supplement 1.

(A) Field view of a representative hippocampal slice showing a surgical cut between DG and CA3. (B) Local D-APV puff application (vertical arrow, two puffs at 0.1 Hz) blocks NMDAR currents recorded at Vh = −50 mV and washes out in less than 10 min (n = 7 cells, five animals, p=5×10−8, paired t-test). Inset depicts the recording paradigm of the experiment (left), the representative NMDAR currents (top) and the summary time course (bottom) where arrows denote the onset of D-APV (2 mM) puff application. Mfs were stimulated with a bipolar electrode (theta-glass pipette) in stratum lucidum in the presence of 100 µM picrotoxin and 10 µM NBQX. (C) D-APV puff application in CA3 did not reduce NMDAR transmission in GCs (n = 6 cells, five animals, control vs D-APV puff, U = 0.594, Mann–Whitney test). Excitatory inputs were stimulated with a monopolar electrode placed in the medial molecular layer/inner molecular layer, in the presence of 100 µM picrotoxin and 10 µM NBQX, while GCs were clamped at Vh = +40 mV. Data are presented as mean ± s.e.m.