Figure 2.

Experimental Timeline and Procedures

(A) The timeline depicts the sequence of pre-treatment evaluation and monitoring, viral vector delivery, and post-treatment evaluation. (B) Two coronal sections indicating the location of the KA injection (back) and depth electrode implantation (front). (C) Typical T2 weighted MRI image of a KA injected rat. A lesion of the hippocampus is visible ipsilateral to the injection (right). The dorsal viral vector delivery location in the hippocampus for this particular animal is shown on the right side. (D) A schematic illustration of distribution of the burr holes and supporting screws on the rat skull: A, cortical electrode; B, depth electrode; C, KA injection, D1 and D2 reference electrodes; E, cement-free area reserved for viral vector delivery; shaded area, area covered with dental cement embedding two screws attached to the skull bone. (E) The number of SRS during the pre-treatment monitoring period was found not to differ between the groups, indicating equal disease severity across the three batches (p = 0.73, Kruskal-Wallis test). (F) The animals were assigned to the treatment groups with the aim of stratifying them for equal mean SRS frequency. Pairs were formed from animals with equal number of SRS, and these were then randomized into the treatment groups. (G) No difference in SRS frequency during 3 weeks of monitoring before treatment indicated a successful stratification of the groups (p = 0.93, Mann-Whitney test). (H) A typical generalized SRS found in the rats during the pre-treatment period. The hippocampal trace (blue) exhibits high amplitude fast-spiking seizure activity before the cortical manifestation of electrographic seizure becomes apparent (black trace), suggesting a focal seizure with secondary generalization.