While most of the animals we observed exhibiting this pattern had cortical electrodes only, the animal shown in Figure 4D Akt inhibitor developed a hippocampal seizure lasting for almost 30 min while exhibiting cortical burst suppression. The animal was moribund during this event, raising the possibility that death in some animals might result from underlying nonconvulsive status epilepticus. The extent of CreERT2-mediated recombination varied among PTEN KO animals, so studies were undertaken to determine whether the percentage of granule cells in which PTEN was deleted correlated with epileptogenesis. Among the eight EEG-recorded PTEN KO mice (aged 3–7 months) for which

good histology was available (e.g., mice that survived and could

be perfusion-fixed), the percentage of dentate granule cells with no detectable PTEN immunoreactivity varied between <1% and 24%. Seizure activity was confirmed in seven of these mice, selleck chemicals llc with PTEN deletion measures of 9%–24%. No seizures were observed in the remaining animal that exhibited few PTEN KO granule cells (<1%). One limitation of the Gli1 promoter used to target hippocampal granule cell progenitors is that subventricular zone progenitors, which populate olfactory bulb via the rostral migratory stream, are also targeted. Cells produced by this pathway differentiate into inhibitory olfactory granule cells (≈95%; OGCs) or olfactory periglomerular cells (≈5%), the majority of which are also GABAergic ( Whitman and Greer, 2009). Although excess growth of inhibitory interneurons may, in principle, be less likely to promote epileptogenesis, it is a formal possibility. To explore this possibility, we first assessed the morphology of OGCs in olfactory bulb from wild-type and PTEN KO mice ( Figure 5). Initially, GFP expression was used to identify OGCs for morphological characterization in the olfactory bulb. Surprisingly,

in olfactory bulb, neither soma area (control, n = 5 [77 cells], 41.1 ± 2.2 μm2; all PTEN KO, n = 4 [44 cells], 47.2 ± 6.8; p = 0.381, t test) nor primary dendrite number (control, n = 5 [77 cells], 3.2 ± 0.2 dendrites/cell; PTEN KO, n = 4 [44 cells], 3.7 ± 0.6; p = 0.353, t test) differed between GFP-expressing OGCs in wild-type and PTEN KO mice. Given the robust morphological impact of PTEN deletion from hippocampal granule cells, we queried whether poor recombination efficiency among GFP expressing OGCs might account for this lack of effect. Analysis of PTEN/GFP double immunostaining revealed that only 44.6% ± 6.5% of GFP-expressing OGCs in PTEN KO mice were also immunonegative for PTEN. By contrast, 84% ± 6.1% of GFP-expressing dentate granule cells in PTEN KO mice were PTEN immunonegative (p = 0.007, t test). These data suggest that cre recombinase is more effective at inducing GFP expression and deleting PTEN from hippocampal granule cells relative to OGCs, although the mechanism of this phenomenon is not clear.