Neuronal network hyperexcitability in tau mouse models. A–G, Hyperexcitability and epileptic seizures in a mouse model of a tauopathy (FTDP-17). Reproduced from García-Cabrero et al. (2013) with permission from Elsevier. A, Intracranial recording of background activity (6–7 Hz) in control mice. B, Spindle-shaped polyspike discharge at 8–10 Hz, during an initial tonic phase (thin arrow indicates the beginning) and a short clonic phase (open arrow signals the beginning) in a FTDP-17 mouse. C, Spontaneous interictal epileptic activity in FTDP-17 mice corresponding to (c1) single spike, (c2) polyspike, (c3) slow wave, and (c4, c5) polyspike-wave discharges. D, Nonconvulsive spontaneous seizure with EEG correlates corresponding to rhythmic, spindle-shaped discharges. E, Spontaneous generalized tonic–clonic seizure in a FTDP-17 mouse manifested in the EEG record as generalized low-frequency (3–6 Hz) poyspike-wave discharge, 36 s in length. Figure shows the records from monopolar electrodes placed over the left frontal cortex with the reference electrodes implanted posterior to λ. F, G, Analysis of seizure latency and length of PTZ-induced generalized seizures in FTDP-17 mice. Mice at three different age spans (1–5, 6–14, and 15–22 months) were injected with a convulsive dose of PTZ (50 mg/kg). F, The time interval between drug administration and development of generalized tonic–clonic seizures and (G) the seizure length were measured. Data are presented as mean ± SEM. Student’s t test was performed for statistical evaluation; *p < 0.05, **p < 0.01, ***p < 0.001 (n = 15–24). H, I, Increased spontaneous synaptic activity in whole-cell patch clamp recordings of layer 3 frontal cortex pyramidal neurons of rTg4510 (hTau P301L) mice. Reproduced with permission from Crimins et al. (2011). Increased frequency of sEPSCs in TG (rTg4510) cells. H, Representative sEPSCs from non-transgenic (NT) and TG cells. I, Bar graphs of mean frequency sEPSCs in NT and TG cells. J, Increased PTZ-induced seizure susceptibility in three-month-old Tau58/4 (htau P301S) mice. Young HET (Tau58/4) mice had higher mean severity scores than WT littermates. Reproduced with permission from Van Erum et al. (2020).