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

DOI: 10.1155/2013/949816

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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. 1. 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]. Nowadays, 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 neurotransmitter gamma-aminobutyric acid and proteins expressed in these cells are allegedly responsible for neuroprotection, increasing resistance to excitatory injury [4]. The DG has been proposed to be a gate for entry of intense neuronal activity into the hippocampus. However, 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 the neuronal activity and, therefore, the seizure propagation through the hippocampus and other limbic system structures [5]. Mossy fiber sprouting

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