Figure 1. MF-SLIN dedepression/LTP is not a mechanistic reversal of LTD.

Time course plot of EPSC amplitude from a representative recording illustrating HFS induced LTP at MF-SLIN synapses that have undergone prior chemical LTD by L-AP4 (400 μM) treatment. Each point represents the peak amplitude of an individual EPSC obtained at the time indicated along the X axis. Traces above are averaged EPSCs (20 consecutive events) obtained at the times indicated (bars 25 pA/20ms). In this and all subsequent time course plots the period of drug application and/or HFS (arrow) are shown at the top of the plot. B. Decimated group data time course plot for experiments similar to that shown in A (n =11). EPSC amplitudes for each recording were binned and averaged (1min. segments) then normalized to the average EPSC amplitude obtained during the baseline period prior to drug treatment. The break in the X axis results from different wash periods (5–10 minutes) following L-AP4 treatment with all recordings being realigned to the 1 minute prior to HFS. C. Representative sample images (top) and records (bottom) illustrating CaT recordings from SLIN targeting MF terminals. Upper panels show wide field (left) and zoomed (right) confocal images of a parent MF bouton with SLIN targeting filipodial extensions loaded with the Ca²⁺ indicator OGB1-AM. The positioning of line scan to monitor presynaptic CaTs is indicated by a line in the right panel. Bottom panels show a single line scan image of a stimulus evoked fluorescence transient (left) and associated CaT (trace at right) plotted as % ΔF/F in time from the average of 4 individual line scan images (bars, 500ms/50% ΔF/F). D. Normalized group data time course plot showing that HFS does not reverse L-AP4-induced CaT LTD (n = 5). Traces above are CaTs obtained from a representative recording obtained at the times indicated (bars, 500ms/20% ΔF/F). DCGIV (1 μM) depression at the end of recordings is used to confirm MF origin of the stimulated axons. E,F Representative recording (E) and normalized group data (F, n = 5) time course plots showing that P/Q type VGCC blockade with AgTx (250 nM) occludes L-AP4 induced LTD of MF-SLIN synapses but does not prevent LTP by HFS given after L-AP4 treatment. Traces above in E are average EPSC pairs (20 HZ) obtained at the times indicated (bars, 25pA/25ms). Inset in E (gray) reveals the boxed region of the plot with expanded Y axis and traces.