Kainic Acid‐Induced Dorsal and Ventral Hippocampal Seizures in Rats
Authors: Akaike Koichi , Tanaka Shigeya , Tojo Hideshi , Fukumoto Shin‐ichiro , Imamurn Shin‐ichi , Takigawa Morikuni 
Published: August 2005

Purpose: Though many previous studies dealing with experimental epilepsy have focused on the amygdala and hippocampus, regional differenccs of dorsal and ventral hippocampus are undefined, We investigated thc electrical and behavioral characteristics of seizures after the iiijection of the kainic acid (KA) into left dorsal hippocampus (LdH) or ventral hippocampus (LvH).

Methods: Twenty male Wistar rats (250 to 300 g) undcrwent stereotactic operation under pcntobarbital anesthesia. A stainless steel screw was placed in contact with the dura over the left sensorimotor cortex (LCx) with an additional screw placed in the frontal sinus as an indiffcrent elcctrodc. In LdH group (KA microinjection into dorsal hippocampus, n = lo), a stainless steel cannula with an inner needle guide was inserted into the LdH in preparation for microinjection. Bipolar depth electrodes were placed into the LdH, LvH, and the left basolatera1 nucleus of the amygdala (LA). In LvH group (KA microinjection into ventral hippocampus, n = lo), likewise, a stainless steel cannula was inserted into the LvH. Bipolar depth electrodes were placed into the LdH, LvH, and LA. All elcctrodes, as well as the cannula, were fixcd in place with dental cement, and the electrodes were connected to a terminal plug attached to the head. The animals were allowed to recovcr unrcstraincd for 7 days after surgery with free access to food and water until the day of the experiment when they were placed i n the recording chamber for behavioral observation and electroencephalographic monitoring. The inner guide was replaced with an injection needle and I.O I J of KA dissolved in phosphate‐buffered saline solution (PBS) at a concentration of 10 pg/pL, was injected into the LdH or LvH (11 = 6, respectively). The rate of injection was 1.0 pL/min. In the control group, 1.0 pL of PBS alone was injected into the LdH or LvH (11 = 4, respectively). The above procedures were done under aseptic conditions. All rats were observed electrophysiologically and be haviorally over 7 days, after which the animals were pcrfused with 10% formalin solution under intraperitoneally administcred deep pentobarbital anesthesia. After fixation and embedding in paraffin, 4 pm coronal sections were cut and processed for microscopic examination including staining with cresyl violet and Luxol fast bluc.

Results: In LdH group, on the electrocncephalogram (EEG), multiple spike discharges initially appeared in LdH and propagated to the LvH and thereafter to the LA (30–60 minutes after KA injection). Thc seizures were morc intense in LvH than LdH. The rats showed immobilization only. In LvH group, on the EEG, multiple spikc discharges appeared sirnultaneously in LvH, LdH, LA, and LCx (20‐40 minutes after KA injection). The rats showed facial twitching, forclimb clonus, circling, rearing, and jumping. LvH seizures were morc likely to spread to LA and LCx than LdH seizures. In controls, no EEG or behavioral changes were seen. Microscopic examination dcmonstratcd focal nccrosis and surrounding gliosis around the tip of the injcction cannula, possihly related to the KA microinjection. In LdH group, netironal damage (CA3) in LdH and LvH was slight. In LvH group, scvere pyknosis (CA3 and hilar neuron) was ohserved in LdH and LvH. In controls, only minimal gliosis along the tracts of the cannula and clectrodes was seen.

Conclusions: On the EEG, LvH seizures rapidly propagated to IA and LCx compared to LdH seizures. Behaviorally, only immobilization was observed in LdH seizures, whereas motor manifestations wcrc dominant in LvH scizures. Pathologic examination revcaled that neu‐ ronal cell damage induced by LvH scizures arc more severe than LdH seizures. These results suggest that LvH seizures are morc likely to involve LA and LCx, and to culminate in intense seizures than LdH scizures, probably caused by interaction of these structures.