Persistent PTD evoked by a single burst of PF firing.

<p><b>A</b>, Schematic diagram of electrode positions in a sagittal cerebellar slice for field potential recording of the PF to PC synaptic transmission. The effect of PF stimulation was recorded extracellularly at least 70 µm vertically below the stimulation electrode. <b>B</b>, Typical field potential evoked by a single PF stimulation. In 10 µM GABAzine (black trace), three negative peaks were resolved. The second negative peak (N2) was abolished in 25 µM NBQX (red trace) and unaltered by the GAGA_A agonist muscimol (10 µM). The N2 peak was assimilated to the field excitatory postsynaptic response (fEPSP). The first negative peak (N1), which remained in NBQX and was abolished in 1 µM TTX, was assimilated to the fiber volley (FV), i.e. the field potential associated to the action potential propagation along PFs. <b>C</b>, The N1 and N2 peaks are respectively 96.2±1.4% and 1.7±0.3% of control in 10 µM NBQX (n = 9). <b>D</b>, Effect of a burst of 10 stimuli at 200 Hz on the recorded field potential. Traces from left to right are averaged field potentials evoked by 15 consecutive stimulations for the 2 min before the burst, 4 consecutive stimulations starting 4 s after the burst, and 15 consecutive stimulations starting 8 min after the burst. A depression of the fEPSP is observed 8–10 min after the burst stimulation. This depression was named persistent PTD (see Text). <b>E</b>, Time course of FV (grey) and fEPSP (black) amplitudes normalized to their averaged values for the 2 min preceding the burst. Only recording showing no detectable change in FV amplitude over their duration are plotted (n = 13). <b>F</b>, Same as in E, but including all the recordings exhibiting an averaged change in the FV amplitude of less than 1%/min (n = 34). Although on average the FV decreased by 5.9±0.8% after 10 min, the fEPSP depression was significantly larger (14±0.8%, n = 34, p = 3·10⁻⁹). <b>G</b>, Average change in fEPSP amplitude plotted against change in FV amplitude. Data obtained from baseline recordings preceding burst stimulation (n = 34). The relationship between FV and fEPSP is sublinear rather than supralinear. <b>H</b>, The persistent PTD is not CB1 receptor-dependent. Synaptic transmission is plotted as fEPSP/FV normalized to the averaged value during the two minutes preceding the burst stimulation. In control condition (n = 34), the burst evokes an SSE (transient 40% depression, see Text) and a persistent PTD (remaining 8% depression until at least 10 min after burst). Following incubation with 2 µM AM251, the SSE (shaded grey) was abolished while the persistent PTD (shaded green) remained unchanged (n = 13). <b>I</b>, Average persistent PTD amplitude 4–6 min (black), 6–8 min (grey) and 8–10 min (dark grey) following the burst, in control and AM251, showing that steady amplitude is reached after 4 min.