Understanding the functional role of mossy fiber sprouting in epileptic patients is pivotal in developing new therapies for this disease. Previous studies have utilized low resolution extracellular and intracellular recording to investigate the functional role of mossy fiber sprouting. This proposal outlines a strategy to use high resolution whole cell voltage clamp recording of excitatory postsynaptic currents (EPSCs) in granule cells evoked with both electrical and photostimulation. The incidence and extent of functional excitatory synapses between granule cells will be investigated under normal conditions and following mossy fiber sprouting in preparations of increasing difficulty and complexity: 1) Kainic acid treated organotypic hippocampal slice cultures; and acute hippocampal slices isolated from 2) Pilocarpine treated rats; and 3) Human epileptic hippocampus. The properties of recurrent excitatory synaptic connections will be examined by determining the proportion of recurrent EPSCs that is mediated by NMDA and nonNMDA glutamate receptors. The effects of GABAergic transmission on recurrent EPSCs also will be investigated. These experiments are designed to determine whether granule cells from functional recurrent excitatory synapses with other granule cells following mossy fiber sprouting and to define the properties of these recurrent excitatory synaptic connections.
