D-serine is required for VC long-term potentiation A: Upper panel shows representative composite current responses of L5PyN for the range of imposed potentials before and during LTP. Scale bars: 300pA, 50ms. Medium panels displays the corresponding total conductance change gT before and during LTP. Lower panels show decomposition of gT into excitatory (gE, black) and inhibitory (gI, grey) conductances (n = 15 cells, 15 slices, 8 animals). Scale bars: 4nS, 50ms. B: Changes in the gT integral (IntgT) calculated every 15 min, up to 1 h post-TBS, show that LTP is abolished by blocking the co-agonist binding site of NMDARs with 7-Cl-KYN, removing D-serine through the D-serine degrading enzyme RgDAAO (n = 18 cells, 18 slices, 9 animals) or preventing D-serine production via blockade of the D-serine producing enzyme serine racemase with Et-Phen (n = 17 cells, 17 slices, 8 animals). This indicates that D-serine is required for VC L5PyNs LTP. C-F: Excitatory (black) and inhibitory (grey) conductances were found to be equally affected by TBS application, regardless of the treatment, indicating that the E-I balance is unaltered by D-serine and LTP. *p<0.05, **p<0.01, ***p<0.001 compared to pre-TBS.