Assessing the role of the hippocampus in amygdala kindled fear : an analysis of environmental habituation

Abstract

Amygdala kindling is commonly used to study the mechanisms involved in epileptogenesis, with long-term amygdala kindling providing a useful model of the behavioural disturbances— such as heightened anxiety— that can occur between epileptic seizures. The purpose of this thesis was to determine whether increased fear behaviours exhibited by long-term amygdala kindled rats are reflective of previously observed kindling-mediated alterations in the hippocampus. As the hippocampus plays an integral role in contextual learning, the ability of the animals to habituate to a novel environment was evaluated, in order to determine if the rats displayed impairments in this hippocampal-dependent function. In Experiment 1, long-term kindled rats demonstrated consistently elevated exploration and fear over repeated exposure to an initially novel open field, indicating impaired habituation. In Experiment 2, all kindled rats showed elevated exploration and an inability to form a home base in relation to static visual cues, again demonstrating an inability to habituate over repeated exposures to the initially novel environment. Rats that had received 30 or 60 stimulations demonstrated hyperexploratory behaviour and elevated fear, although this behaviour did dissipate to a certain degree by the final day of testing. Long-term kindled rats, having received 99 stimulations, demonstrated extremely heightened fear behaviours that interfered with normal exploration, home base formation and habituation. These fear behaviours included high levels of freezing, disorganized running, and purposive jumping from the open field. Taken together, these results indicate that long-term amygdala kindling does produce deficits in habituation to an initially novel environment. As habituation necessarily involves the hippocampal-dependent roles of contextual learning and memory, the current research suggests that long-term kindling does impair hippocampal function and that this may contribute to kindling-induced fear behaviours. This research may help to understand the mechanisms involved in emotional disturbances experienced by human epileptics.