Dorsal hippocampal kindling produces a selective and enduring disruption of hippocampally mediated behavior

Abstract

Kindling produces enduring neural changes that are subsequently manifest in enhanced susceptibility to seizure-evoking stimuli and alterations in some types of behavior. The present study investigated the effects of dorsal hippocampal (dHPC) kindling on a variety of behaviors to clarify the nature of previously reported effects on spatial task performance. Rats were kindled twice daily with dHPC stimulation until three fully generalized seizures were evoked. Beginning 7 d later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task, and a delayed-match-to-place (DMTP) task in a water maze to assess anxiety-related and activity-related behavior (tasks 1 and 2), object recognition memory (task 3), and spatial cognition (task 4). Kindling disrupted performance on the DMTP task in a manner that was not delay dependent and produced a mild enhancement of activity-related behaviors in the open field task but not the elevated plus maze. All other aspects of testing were spared. These findings indicate that dHPC kindling produces enduring and selective effects on behavior that are consistent with a restricted disruption of hippocampally mediated functions. Possible bases for these effects are changes in local NMDA receptor function and/or changes in local inhibition, which might alter the optimal conditions for experience-dependent induction of intrahippocampal plasticity. This preparation may be useful for studying the mechanisms of mnemonic dysfunction associated with temporal lobe epilepsy and may offer unique insights into the mechanisms underlying normal hippocampal function.

Fig. 1.

Measures of activity–exploration in the elevated plus maze. Kindled and control groups (both nvalues = 13) were tested 7 d after the completion of kindling. Data are presented as means ± SEM. Total Entries, Total number of entries to all arms in the maze.

Fig. 2.

Measures of anxiety in the elevated plus maze. Testing took place 7 d after the completion of kindling. Data are presented as means ± SEM. Entry Ratio, Number of open arm entries per number of closed arm entries; Dwell Ratio, time in open arms per trial duration.

Fig. 3.

Measures of anxiety in the open field task. Data are from day 1 of open field testing, 8 d after the completion of kindling, and are presented as means ± SEM.Entries, Number of entries to the central ring of the open field; Dwell Time, time spent in the central ring of the open field.

Fig. 4.

Measures of activity–exploration in the open field task. Data are from day 1 of open field testing, 8 d after the completion of kindling, and are presented as means ± SEM. Object Dwell Times, Time spent exploring the two objects placed in the open field. *p < 0.05 relative to control performance; one-tailed ttest.

Fig. 5.

Performance on measures of object recognition memory in the object exploration open field task, 12 d after the completion of kindling. Data are means ± SEM. Dashed line represents chance levels of performance.Entries, Ratio of number of bouts of exploration of the novel object per number of bouts of exploration of the familiar object.Dwell Time, Ratio of time spent exploring the novel object per time spent exploring the familiar object. #p < 0.05 relative to chance performance.

Fig. 6.

Latency to escape to the hidden platform on matching trials 1 (A), 2 (B), and 3 (C) during delay phase of testing on the DMTP task in the MWM, 18–23 d after kindling. Data are averaged across 2 d of testing at each delay and are presented as means ± SEM. *p < 0.05 relative to control performance.

Fig. 7.

Direct swims to the hidden platform on matching trials 1 (A), 2 (B), and 3 (C) during delay phase of testing on the DMTP task in the MWM, 18–23 d after kindling. Data are averaged across 2 d of testing at each delay and are presented as means ± SEM. A direct swim was scored if the rat remained within a 25 cm alley from the start position to the platform. *p < 0.05 relative to control performance.