RETROHIPPOCAMPAL CIRCUITS MEDIATED EPILEPTIFORM ACTIVITY

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DESCRIPTION: (Adapted from the Investigator's Abstract): The entorhinal cortex can generate epileptiform activity independent of the hippocampus, it can sustain epileptiform activity generated in the hippocampus, and it gates the spread of such activity to the neocortex. While there has been intensive work on the basis for epileptiform activity in CA3 and some phenomenological studies of the interactions of entorhinal and hippocampal seizure generators, there has been virtually no attention paid to the mechanism by which the retrohippocampal areas generate seizure activity themselves. Part of the reason for this has been a lack of data on the fundamental circuitry and cellular properties of retrohippocampal cells. Our laboratory has been studying the cells and circuits of the retrohippocampal regions, including entorhinal cortex, presubiculum, parasubiculum and subiculum. The aim of this project is to define the cells and intrinsic circuits of the entorhinal cortex and to identify their roles in the generation of epileptiform discharges. Our overall hypothesis is that epileptiform events (interictal spikes and after discharges) are generated in entorhinal cortex by a combination of intralaminar and interlaminar excitatory connections not found in other retrohippocampal or hippocampal structures. Single neurons will be electrophysiologically and morphologically characterized. The properties of unitary and compound excitatory postsynaptic potentials will be examined in identified cells. The cellular and synaptic properties of identified neurons will be correlated with their activity during epileptiform discharges in disinhibited slices. The results will provide fundamental data on the basic properties of cells in the entorhinal cortex and its intrinsic connectivity. These data will be part of the foundation for understanding the normal and abnormal physiology of the retrohippocampal regions. The properties of these cells and circuits they form in one model of epilepsy (that seen during disinhibition) will demonstrate some of the functional properties of the circuitry. These functional properties will provide critical insights into epileptogenesis and the spread of seizure activity in the entorhinal cortex. An understanding of such circuits may lead to practical strategies for limiting seizure generation and spread by targeted disconnection procedures.