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Characterization of conditioned effects in the kindling model of epilepsy and neuroplasticity Barnes, Steven John


Mild periodic electrical stimulation to any one of many brain sites leads to the development and progressive intensification of elicited convulsions. This "kindling phenomenon" has been widely studied as a model of epilepsy and neuroplasticity. We recently discovered that subjects in conventional kindling experiments learn the relationship between the stimulation environment and the subsequent stimulation and convulsion and that this conditioning has significant effects on both their convulsions and interictal (between convulsions) behaviour. Specifically, the convulsions of rats kindled from the basolateral amygdala (BA) were more severe in an environment in which they had always been stimulated than in an environment in which they had never been stimulated, and they displayed more interictal defensive behaviour in the stimulation environment. The objective of the present experiments was to establish the reliability, generality, nature, and theoretical significance of this discovery. This thesis comprises three different lines of experiments. The first line confirmed that the effects of the stimulation environment observed during BA kindling are the result of Pavlovian conditioning. The second line explored the conditioned effects associated with the kindling of brain structures other than the BA; the results suggested that kindling site determines the conditioned effects of the stimulation environment on convulsions and interictal behaviour. The third line demonstrated that conditioned effects contribute substantially to two of the defining features of the kindling phenomenon: its permanence (If a rat is left unstimulated for several months, fully generalized convulsions are quickly elicited once kindling recommences.) and its "transfer" between brain sites (If a rat is kindled from one brain site, it subsequently requires fewer stimulations to kindle from a second brain site.). The present results not only characterize the conditioned effects of kindling, they also indicate that such effects are a general and reliable component of kindling. Clearly, the key to discovering the mechanisms underlying kindling lies, to a large degree, in the interactions of the subjects with the cues that predict each stimulation and not solely in the unconditioned consequences of the brain stimulations and convulsions.

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