Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




Dr. R.J. Racine


In the adult nervous system, neuroplasticity can be described as all modifications in neuronal structure or function in response to alterations in input. The kindling model of temporal lobe epilepsy represents one of the most widely studied models of neuroplasticity in the mature nervous system. Kindling can be defined as a progressive increase in evoked behavioural and electrographic seizure activity following electrical stimulation of forebrain structures. Recent research has shown that kindling produces a number of plastic changes in the brain, particularly in the hippocampal region. These changes include sprouting of axons, an increase in the size of the hilar area of the dentate gyrus, and reactive gliosis. To date, the relationship between kindling and kindling-induced hippocampal plasticity is not clear. The major emphasis of this thesis is to investigate whether kindling-induced plasticity can be induced by activation. In Study 1, the neurotrophin nerve growth factor (NGF) was used as a tool to dissociate kindling-induced cell loss and kindling-induced mossy fiber sprouting. Intravetricular administration of NGF accelerated seizure development, enhanced mossy fiber sprouting and attentuated seizure-induced decreases in hilar cell density. These findings appear to dissociate kindling-induced mossy fiber sprouting is due to the co-involvement of growth factors and activation. Study 2 showed that NGF may mediate kindling-induced mossy fiber sprouting via the cholinergic system, providing the first evidence that the cholinergic system plays a role in mossy fiber sprouting. Study 3 showed that mossy fiber sprouting can be induced by non-epileptogenic stimulation, providing further evidence that mossy fiber sprouting can occur in the absence of neuronal damage. Study 4 showed that kindling-induced changes in hilar area and kindling-induced changes in hilar area and kindling-induced reactive gliosis follow a similar time course.

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