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Dentate gyrus network reorganization during medial temporal lobe epilepsy leads to dysfunctional dentate neural network in rats

Abstract

Theoretical models have suggested that the dentate gyrus (DG) plays a significant role in pattern separation, an important neural-network computation that is critical for memory formation. Patients with medial temporal lobe epilepsy (MTLE), defined by having chronic unprovoked seizures, typically complain of memory impairments. There are many distinct anatomical changes that occur in many MTLE patients, including mossy fiber (mf) sprouting from hippocampal region the DGs granule cells. It is unknown as to whether the observed anatomical reorganization that occurs in the development of MTLE contributes to changes in dentate network function and consequently memory impairments. I therefore proposed to test network functions of the DG in a rat model of MTLE. In this study we looked at the permanent anatomical changes (mf sprouting) of the DG in relation to the functional changes (pattern separation) of the DG network and its downstream target, cornu ammonis region 3 (CA3), in awake-behaving animals. Experiments testing the ability of the dentate network to pattern separate included rats foraging in a series of square and circular environments, while electroencephalograph and extracellular action potentials were recorded. The results showed that the increased amount of pathological reorganization found in the DG (mf sprouting) correlated with the DG cell populations' impaired ability to pattern separate. However, there was no effect on the CA3 region in epileptic rats when compared to control rats

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