4-Aminopyridine Induces Network-Driven Bursting in Subiculum Minislices in an Animal Model of Temporal Lobe Epilepsy
Abstract number :
3.018
Submission category :
Translational Research-Basic Mechanisms
Year :
2006
Submission ID :
6704
Source :
www.aesnet.org
Presentation date :
12/1/2006 12:00:00 AM
Published date :
Nov 30, 2006, 06:00 AM
Authors :
1Giulia Curia, 1Ruba Benini, and 1,2Massimo Avoli
Temporal lobe epilepsy (TLE) is the most common form of partial complex seizures in humans. For several years neuroscientists have focused on investigating network and intrinsic properties of the hippocampus proper, and its role in TLE. Recently however, they have been giving more importance to parahippocampal structures, including the subiculum. Subiculum is the closest structure to the hippocampus; it receives inputs from the hippocampus proper and projects to the entorhinal cortex., The brain was quickly removed from adult rats and cut into slices (450 [mu]m thickness) that initially included the hippocampus and adjacent enthorinal cortex. The subiculum was further isolated from these slices by cutting out the CA1, dentate gyrus, pre- and para-subiculum and enthorinal cortex. We performed extra- and intracellular recordings from isolated subiculum minislices obtained from both non-epileptic controls (NEC) and pilocarpine-treated rats, which represents an animal model of TLE., In subiculum minislices, application of 4-aminopyridine (4-AP) induced spontaneous network activity in both NEC (interval of occurrence: 85.71[plusmn]10.56 s; duration: 0.78[plusmn]0.06 s; n=15) and pilocarpine-treated (interval of occurrence: 73.35[plusmn]8.74 s; duration 0.64[plusmn]0.01 s; n=7) animals. Intracellular recordings revealed that subicular cells at resting membrane potential exhibited three different types of spontaneous network activity. In the first group, field activity corresponded intracellulary to an initial hyperpolarization followed by a long-lasting depolarization (LLD). In the second group, the LLD was preceded by an initial depolarization leading to one or more action potentials. Finally, in the third group, an initial burst discharge was found to precede the LLD. In both NEC and pilocarpine-treated tissue, all three types of activity were contributed by GABA[sub]A[/sub] receptors since the activity is markedly reduced by picrotoxin. Comparison of NEC and pilocarpine-treated tissue revealed a difference in the expression of these three types of activity. In NEC, 71.43% of the cells, demonstrated the first situation (n=10/14); this percentage dropped to 57.14% in pilocarpine-treated animals (n=4/7). The second situation occurred in 21.43% of NEC (n=3/14) and in 14.28% of pilocarpine (n=1/7). The third situation was present only in 7.14% of NEC (n=1/14) but in 28.57% of pilocarpine-treated rodents (n=2/7)., These data demonstrate that 4-AP induces network-driven events in subicular minislices of both NEC and pilocarpine-treated rats. In addition, subicular cells from epileptic tissue are more likely to exhibit network-driven burst discharges as compared to those from NEC., (Supported by CIHR, FXRFC, CURE and FRSQ.)
Translational Research