Figure 1.
Exposure to Aβo causes an increase in glutamate release probability that is required for the Aβo-dependent augmentation of hippocampal LTD
(A) Schematic showing protocol for determining kinetics of FM1-43 release from presynaptic terminals.
(B) Left panel: sample image of FM dye-labeled presynaptic terminals in CA1 of an organotypic hippocampal slice. Right panels: sample time-lapse images demonstrating stimulus-driven dye loss at synaptic puncta under conditions indicated. Arrow indicates onset of stimulation. Scale bars = 5 μm.
(C) Average FM1-43 destaining plots fitted with first-order exponential decay curves.
(D) Average time constants of destaining (control: n = 217 puncta from 6 slices, τ = 400.5 ± 14.6 s; Aβo: n = 283 puncta from 6 slices, τ = 268.3 ± 7.0 s).
(E) Frequency distribution of destaining time constants from individual puncta showing clear right shift following Aβo treatment.
(F) Experimental setup for plasticity experiments with acute hippocampal slices incubated in the indicated conditions for at least 2 h before recording field EPSPs from CA3-CA1 synapses.
(G) Summary traces showing LTD following a low-frequency stimulation protocol (900 × 1 Hz). Traces normalized to pre-induction baseline.
(H) Mean average fEPSP slopes calculated within a 55- to 60-min time window after LTD induction. Inset traces represent fEPSPs before (gray) and after (black) LTD induction; scale bars: 0.5 mV, 5 ms (control: n = 7, 77.26% ± 4.79% baseline fEPSP; Aβo: n = 8, 41.46% ± 9.08% baseline fEPSP; AgTx: n = 5, 80.26% ± 8.99% baseline fEPSP; AgTx + Aβo: n = 6, 76.08% ± 4.64% baseline fEPSP).
Kruskal-Wallis test followed by Dunn’s multiple comparison test versus control. Error bars represent ± SEM. ∗p < 0.05, ∗∗∗p < 0.001.