Enhanced Synaptic Connectivity in the Dentate Gyrus during Epileptiform Activity: Network Simulation

Keite Lira De Almeida França,Esper Abrão Cavalheiro,Antonio Fernando Catelli Infantosi,Gilcélio Amaral Da Silveira,Mario Antônio Duarte,Fulvio Alexandre Scorza,Ricardo Mario Arida,Antônio-Carlos Guimarães De Almeida,Antônio Márcio Rodrigues

doi:10.1155/2013/949816

Abstract

Structural rearrangement of the dentate gyrus has been described as the underlying cause of many types of epilepsies, particularly temporal lobe epilepsy. It is said to occur when aberrant connections are established in the damaged hippocampus, as described in human epilepsy and experimental models. Computer modelling of the dentate gyrus circuitry and the corresponding structural changes has been used to understand how abnormal mossy fibre sprouting can subserve seizure generation observed in experimental models when epileptogenesis is induced by status epilepticus. The model follows the McCulloch-Pitts formalism including the representation of the nonsynaptic mechanisms. The neuronal network comprised granule cells, mossy cells, and interneurons. The compensation theory and the Hebbian and anti-Hebbian rules were used to describe the structural rearrangement including the effects of the nonsynaptic mechanisms on the neuronal activity. The simulations were based on neuroanatomic data and on the connectivity pattern between the cells represented. The results suggest that there is a joint action of the compensation theory and Hebbian rules during the inflammatory process that accompanies the status epilepticus. The structural rearrangement simulated for the dentate gyrus circuitry promotes speculation about the formation of the abnormal mossy fiber sprouting and its role in epileptic seizures.

Highlights

Epileptic syndromes are a group of neurological disorders with different etiology and clinics characterized by recurrent seizures with excessive and hypersynchronous neuronal activity [1]
For the stimulations performed in the simulations (ii) and (iii), the stimulus was applied at the day 1.5, with α = 1.0, during 70 min
The stimulus intensity was adjusted to be less intense but sufficient to induce maximal activation of the network. This procedure took into account the objective of representing the experimental protocols of drug applications in animals to induce epileptiform seizures and, the status epilepticus [27,28,29]

Summary

Introduction

Epileptic syndromes are a group of neurological disorders with different etiology and clinics characterized by recurrent seizures with excessive and hypersynchronous neuronal activity [1]. Approximately 50 million people are affected with epilepsy and 40% of which are classified as temporal lobe epilepsy (TLE) [2]. The human TLE is frequently associated with neuronal loss in the hippocampus and dentate gyrus (DG) [3]. Throughout this degeneration, called hippocampal sclerosis, the granule cells are less affected. The DG has been proposed to be a gate for entry of intense neuronal activity into the hippocampus. In TLE, the synaptic reorganization involving the DG granule cells (abnormal sprouting of hippocampal mossy fibers) may act to reduce the DG filtration properties, increasing the propensity to intensify

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