Over the past two decades basic and clinical neuroscientists have become interested in the anatomic and physiological changes in the central nervous system induced by neuronal activity. These changes, categorized as """"""""neural plasticity"""""""" are believed to explain many normal phenomena, such as learning and memory. However, changes in brain structure and function may also be induced by pathological neuronal activity. There is an emerging literature suggesting that the excessive neuronal discharges associated with epilepsy can alter the structure of neurons without leading to neuronal death, but no one has determined the extent or the reversibility of these changes in single, identified central neurons. There are now optical techniques and transgenic mice expressing the green fluorescent protein (GFP) and variants that allow """"""""online"""""""" tracking of the morphological changes in single neurons during and after in vivo and in vitro seizures. The experiments proposed in this application will begin to test the hypothesis that prolonged seizure discharges can alter the morphology of spines and dendrites in single neurons imaged in real time and that these changes may play a role in the termination of some types of seizures. These are important issues to resolve, because there is an ongoing controversy about the structural and functional consequences of different types of seizure disorders. More conventional histological analysis, which readily identifies neuronal death, lacks the power to resolve questions about subtle anatomic alterations at the level of single neurons and processes. This work is still in an exploratory stage, because the exact parameters required for long term imaging of in vivo and in vitro seizures have not been determined. When the exploaratory work described in this application has been carried out, it should be feasible to begin isolating the individual variables that account for seizure-induced neuronal alterations. This information will be essential in informing debate about more aggressive therapy for specific types of epilepsy.
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