Simultaneous video/electroencephalography (EEG) recordings were made from either hippocampus or cortex of control (n = 9) and PTEN KO mice (n = 14) using 2-lead wireless EEG transmitters beginning at ≈6–8 weeks of age. Four additional animals (n = 1 control, three PTEN KO) were recorded simultaneously from hippocampus

Tyrosine Kinase Inhibitor Library and ipsilateral motor cortex using 4-lead wireless transmitters. A total of 96 days of video/EEG data was collected from control animals and 112 days collected from PTEN KO animals. Strikingly, 82% of PTEN KO mice exhibited spontaneous seizures. Two of the three animals that did not exhibit seizures died after only 4 days of recording, so whether they would have exhibited seizures eventually is not known. Many animals exhibited seizures during

GSK126 cost the first week of recording (≈6–8 weeks of age), indicating that epilepsy can develop in these mice in as little as 4 weeks after tamoxifen injection. No seizures were observed in any control animals. In PTEN KO animals followed over a period of weeks, the seizure phenotype was progressive. Initially (≈8 weeks), animals exhibited relatively frequent epileptiform activity (e.g., brief spike trains with no change in frequency) and occasional stereotypical seizures, characterized by progressive changes in frequency and amplitude before terminating after about 30–60 s ( Figure 4A). In animals recorded from hippocampus and cortex simultaneously, epileptiform activity and seizures were consistently observed in hippocampus hours to days before abnormalities were evident in the cortical EEG ( Figure 4B). Animals were typically immobile during these focal hippocampal seizures. As the animals became older, EEG abnormalities became more severe. Some animals exhibited more frequent stereotypical seizures, which were associated with convulsions when they spread to cortex ( Figure 4C). Other animals exhibited fewer

overt seizures but began to exhibit increasing amounts of abnormal background activity and interictal spikes. Over time abnormal activity typically devolved to intermittent bursting ( Figure 4D) or burst suppression patterns P-type ATPase ( Figure 4E), and manifested in both hippocampus and cortex. Latencies between bursts ranged from about 1–60 s. Periods of burst suppression could persist for 20–30 min or longer, during which animals were largely immobile. Normalization of the EEG in these animals was followed by a return to normal behavior. PTEN KO animals exhibiting burst suppression patterns exhibited poor grooming and declining health. Ten of 17 PTEN KO mice became moribund and were euthanized or died prematurely, compared to only one of ten EEG implanted control mice. Mean age for morbidity/mortality among PTEN KO mice was 2.2 months.