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. 2018 Dec 12;38(50):10595–10606. doi: 10.1523/JNEUROSCI.1700-18.2018

Figure 1.

Figure 1.

Soluble P301S tau aggregates, but not monomers or fibrils, potently inhibit LTP in vivo. A, Negative contrast electron micrographs of P301S tau monomers, fibrils and SτAs. Scale bar, 100 nm. B, ThT binding of P301S tau monomers (Mon), fibrils (Fib), and SτAs (3 technical replicates in each group). C, Particle size distribution, peaking at ∼50 nm, for SτAs using DLS (average of 3 technical replicates). D, E, Synaptic field EPSPs recorded in the CA1 area of anesthetized rats injected with (D) Veh (black diamonds; n = 5), P301S tau monomers (16 pmol; open squares; n = 4), P301S tau fibrils (23 pmol; gray circles; n = 4) or (E) different doses of P301S SτAs: 0.28 pmol (gray circles; n = 7), 1.4 pmol (open squares; n = 5), or 2.8 pmol (black triangles; n = 5). To induce LTP, HFS (arrow at time 0) was applied 15 min after intracerebroventricular injection (open triangle). Sample traces were recorded 10 min before (dotted line) and 3 h after HFS (solid line). F, Summary bar charts showing the magnitude of LTP during the last 10 min for data in D and E. Numbers in brackets represent dose (in pmol) of injected preparations. G, Burst responses during the HFS (10 trains of 20 pulses at 200 Hz with a 2 s intertrain interval). Change in the burst response (compound EPSP integral) evoked by each train of stimuli, expressed as a percentage of the first burst response in animals pretreated with either Veh (black circles) or P301S SτA (open squares; n = 5 per group). H, Summary bar charts showing the magnitude of LTP induced by a stronger HFS protocol (sHFS; consisting of 3 sets of HFS at high intensity) in Veh and P301S SτAs-treated groups (n = 4 for both groups). I–K, Baseline excitatory transmission was recorded for >3 h after injection of Veh (black circles; n = 5) or P301S SτAs (open squares; n = 6). Summary bar charts of EPSP amplitude (J) and PPF (40 ms interstimulus interval) ratios (EPSP2/EPSP1; K) at 3 h postinjection. Values are mean ± SEM. Scale bars: vertical, 2 mV; horizontal, 10 ms. #p < 0.05, ##p < 0.01 compared with pre-HFS, paired t test; **p < 0.01, ****p < 0.0001, two-way ANOVA with repeated-measures followed by Dunnett's multiple-comparison tests versus Veh group.