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Date of Award

4-1985

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

G.K. Smith

Abstract

Repeated electrical stimulation of certain brain sites in animals leads to the progressive development of clinical seizures, a phenomenon known as kindling. The basic neuronal mechanisms underlying this effect may be similar to those involved in human epilepsy, but are not well understood. We have examined the properties of single neurones and populations of neurones in hippocampal slices derived from rats kindled in the hippocampus, fimbria/fornix, perforant path, or amygdala, and compared them with those of unstimulated animals.

At the neuronal population level, tissue from kindled rats did not display an increased tendency to generate spontaneous epileptiform activity. This as also the finding in ionic substitution experiments, where the levels of extracellular potassium were increased as high as 9 mEq/1. Electrical stimulation of afferents to the CA1 region evoked synaptically-mediated population responses which were similar to those of controls, except for tissue derived from rats kindled in the fimbria or in the amygdala. In these experiments, there was a tendency for multiple population spikes to appear in the responses to stimulation and this may reflect an increased excitability of the neuronal population.

Intracellular studies of hippocampal CA1 neurones from amygdala-kindled rats revealed that the basic activity and passive membrane properties did not differ from those of controls. However, the amplitude of the afterhyperpolarization following synaptic activation was increased in these neurones. In addition, the response to intracellular injection of depolarizing current was altered in some neurones, observed as an increased action potential discharge during the initial phase of depolarization.

These findings are discussed in terms of an apparent immunity of the hippocampus towards the development of chronic epileptogenic properties, and the ionic and membrane mechanisms which may be responsible for the observed differences between kindled and unkindled tissue.

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