Extended Data Fig. 6: Recovery of LHb NMDAR-eEPSCs after washout of ketamine in presence of endocytosis blocker Dyngo-4a.
From: Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb
a, Dyngo-4a successfully blocks LFS (1 Hz, 15 min)-induced, endocytosis-based long-term depression of NMDAR-eEPSCs in hippocampal CA1 neurons. NMDAR-eEPSCs are isolated by application of PTX and NBQX in Mg2+ free ACSF under voltage clamp at −70 mV. In the Dyngo-4a group, 30 μM Dyngo-4a is additionally added in ACSF throughout the recording. b, d, In presence of Dyngo-4a, LHb NMDAR-eEPSCs (normalized by baseline) still do not show recovery after wash-out of 100 μM ketamine (b) or 10 μM ketamine (d) in LHb neurons. c, e, Bar graphs showing NMDAR-eEPSCs at the end of the 10 min perfusion period (left) and at 50–60 min (right). Ket: ketamine. The data of vehicle group in (b) was from the data of ket- group in Fig. 3a and the data of vehicle group in (d) was from the data of “no stimulus” group in Fig. 4a. NS, not significant. Error bars indicate SEMs. (see Supplementary Table 1 for statistical analyses and n numbers).
