Fig. 6: NMDAR-dependent LTD is associated to a frequency stimulation facilitation without affecting release probability. | Nature Communications

Fig. 6: NMDAR-dependent LTD is associated to a frequency stimulation facilitation without affecting release probability.

From: NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95

Fig. 6

A Representative traces of synaptic EPSCs in response to 5 stimulations at 20 Hz before (dark line) and 30 min after (blue line) NMDAR treatment. B Paired-average amplitude of the first response before and 30 min after treatment (n = 9 cells, mean ± SEM, paired t-test, p = 0.0263). The decrease of the first response demonstrates the efficiency of the LTD protocol. C Average of the 5 EPSC amplitudes, normalized by the first response intensity (n = 9 cells, mean ± SEM, two-way ANOVA. For PPR variation, F(4,32) = 10.36, p < 0.0001, Dunnett’s post-test found significant differences increase of PPR between PPR1/1 and PPR2/1, p = 0.0234 at basal state, and between PPR1/1 and either PPR2/1, PPR3/1, PPR4/1 or PPR5/1, p < 0.0001, 30 min after NMDAR-dependent LTD induction. For basal state vs NMDAR-dependent LTD, F(1,8) = 12.85, p = 0.0071 and Sidak’s post-test found significant difference between the basal state and 30 min after NMDAR-dependent LTD induction for PPR2/1, PPR3/1, PPR4/1 and PPR5/1, p = 0.0011, p = 0.0013, p < 0.0001 and p < 0.0001 respectively). A clear facilitation of the currents appears after induction of a NMDAR-dependent LTD. D–F Similar experiments has been realized when LTD is induced by ATP application, with example of traces in (D). The significant decrease of the first response represented in (E) validate the depression of the synaptic response (n = 10 cells, mean ± SEM, paired t-test, p = 0.0012). The average of the 5 responses (F) reveals no facilitation compared to control condition after ATP treatment (n = 10 cells, mean ± SEM, two-way ANOVA. For PPR variation, F(4,36) = 7.73, p < 0.0001, Dunnett’s post-test found significant differences increase of PPR between PPR1/1 and PPR2/1, p = 0.0163 at basal state, and between PPR1/1 and PPR2/1 or PPR3/1, p < 0.0004 and p = 0.0138 for P2XR-dependent LTD. For basal state vs P2XR-dependent LTD, F(1,9) = 1.197, p = 0.03023). G Example of the fluorescence increase at a synapse expressing iGluSnFR construct during a field stimulation. Responding synapses are labelled with an arrow (upper part). At the bottom, example of the ∆F/F signal obtained at a single synapse. Stars indicate when the synapse is considered as stimulated (scale bar = 2 µm). H Cumulative distribution of the release probability per synapse in control condition (black line) or after LTD induction with either NMDA (Blue line) or ATP (red line) treatment. The mean values per recorded dendrites has been represented in the insert with the same color code. None of the conditions affects significantly the release probability (n = 64, 44 and 22 respectively, mean ± SEM, one-way ANOVA, p = 0.1520). I Representative traces of synaptic EPSCs in response to 2 stimulations at 20 Hz before (dark line) and 30 min after (blue line) LFS protocol. J Paired-average amplitude of the first response before and 30 min after treatment (n = 19 cells, paired t-test, p = 0.0009). The decrease of the first response demonstrates the efficiency of the LTD protocol. K Average of the paired-pulse ratio before and 30 min after LFS-induced LTD (n = 15; paired t-test, p = 0.046).

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