Original recordings of excitatory postsynaptic currents (EPSCs) evoked in individual CA1 pyramidal cells before and after theta burst stimulation (TBS). The individual neurons were recorded in (a) a control hippocampal slice pretreated with recombinant tau monomer, (b) in a hippocampal slice pretreated with recombinant tau oligomers, (c) in a hippocampal slice pretreated with brain-derived tau oligomers, and (d) in a hippocampal slice pretreated with brain-derived tau oligomers preincubated with tau oligomer-specific antibody (T22). Each trace is the average of 8–10 EPSCs. Scale bars, 100 pA, 10 ms. (e) Time course of LTP averaged across the sample of neurons recorded in (a, n = 6 neurons), (b, n = 5 neurons), (c, n = 7 neurons), and (d, n = 6 neurons). Each symbol shows the mean ± SEM of 10 EPSCs at every 30 s. Brain-derived tau oligomers, but not brain-derived PHF, impair object recognition memory in vivo. (f) Brain-derived tau oligomers and PHF isolated and characterized as shown in were injected into the hippocampus bilaterally (0.6 µg each). Mice were tested 3 days post injection. Mice injected with PBS, and PHF spent significantly more time investigating the novel object, whereas mice injected with brain-derived tau oligomers showed memory impairment, as evidenced by their inability to recognize the novel object and hence spending equal time investigating both objects. (g) Histograms show the discrimination index corresponding to the data in (f).