Fig. 2.
Effects KCC2 blockers and enhancers on LTP and its synapse specificity in young and old slices (also see Supplemetary Table3). Preincubation of young (n=7) with the KCC2 blocker VU0240551 (10μM, for 1hr) only slightly affected LTP (a) but spread the potentiation to untetanized synapses (b). Preincubation of young (n=11) with the KCC2 enhancer CLP-257 (100μM, for 1hr) did not affect the tetanized (S1) (a) or untetanized (S2) (b) responses. Enhancing KCC2 activity with CLP-257 (100μM, for 1hr) in old (n=6) did not affect LTP magnitude in the tetanized pathway (S1) (a), but significantly stopped the spread of potentiation to untetanized synapses (b). Blocking KCC2 in old slices (n=4) with VU0240551 (10μM, for 1hr) did not change LTP of S1 (a) or its spread to S2 (b). Insets show example traces from the time points marked by “1” and “2”. Calibration bars 0.5mV, 5ms. (c) Lack of correlation between the magnitude of LTP of the tetanized pathway (S1) and that of the untetanized pathway (S2). The average potentiation of the fEPSP slopes during 35-40 min after TBS (fEPSP35-40) of the untetanized (S2) responses are plotted against the tetanized (S1) responses in young and old slices under three different conditions (Ctrl: control, VU:10 μM VU0240551, and CLP: 100μM CLP257). Legends indicate Pearson's correlation coefficients r and their p values according to a two-tailed t-test. Large symbols represent means of the x-y data and the shaded ovals are drawn at 1 × S.D. levels. The dotted lines at x=1 and y=1 indicate no potentiation. Symbols to the right of the x=1 line indicate LTP of S1, above the y=1 line indicate LTP of S2, and those above both lines show LTP of both S1 and S2.