Morphological alterations in GABA neurons in temporal lobe epilepsy are complex and involve the loss of some groups of GABA neurons and the preservation of others. While previous studies have focused primarily on the loss of cell bodies of GABA neurons in epilepsy models, the present studies will examine changes in the distributions of GABAergic axons and terminals. The studies will determine if axonal reorganization of GABA neurons, similar to that of excitatory neurons, occurs in the hippocampal formation in a pilocarpine-treated mouse model of recurrent seizures. The following questions will be addressed: 1) Do remaining somatostatin/GABA neurons in CA1 exhibit axonal reorganization and form an aberrant GABAergic innervation of the molecular layer of the dentate gyrus? Such changes could alter the effectiveness and timing of inhibition in the dentate gyrus. 2) Is a distinct group of GABAergic basket cells that contain cholecystokinin damaged during status epilepticus, and is a loss of these neurons followed by axonal sprouting of a different group of basket cells that express parvalbumin? Such changes could alter the balance between functionally different groups of basket cells and thus alter the inhibitory processes. 3) Is there a maintained reduction of GABAergic fibers in two major dendritic regions of the hippocampus, and is this decreased GABAergic innervation the result of preferential loss of bistratified neurons that innervate the regions? A combination of light and electron microscopic immunohistochemical methods will be used to study the sequential changes of specific groups of GABAergic axons in order to provide solid evidence for initial degeneration of axon terminals and subsequent reorganization or sprouting of GABAergic axons. The results of these studies could help provide an explanation for the paradoxical findings of a substantial loss of some groups of GABA neurons in the hippocampal formation and yet an abundance of GABAergic fibers in the region in temporal lobe epilepsy. The studies could provide new evidence for GABA neuron plasticity in epilepsy that, rather than reducing epileptiform activity, could contribute to the epilepsy process through aberrant inhibitory circuits. ? ?
