Abstract

Kainic acid-induced status epilepticus (KA-SE) in mature rats results in the development of spontaneous recurrent seizures and a pattern of cell death resembling hippocampal sclerosis in patients with temporal lobe epilepsy. In contrast, KA-SE in young animals before postnatal day (P) 18 is less likely to cause cell death or epilepsy. To investigate whether changes in neuronal excitability occur in the subiculum after KA-SE, we examined the age-dependent effects of SE on the bursting neurons of subiculum, the major output region of the hippocampus. Patch-clamp recordings were used to monitor bursting in pyramidal neurons in the subiculum of rat hippocampal slices. Neurons were studied either one or 2-3 weeks following injection of KA or saline (control) in immature (P15) or more mature (P30) rats, which differ in their sensitivity to KA as well as the long-term sequelae of the KA-SE. A significantly greater proportion of subicular pyramidal neurons from P15 rats were strong-bursting neurons and showed increased frequency-dependent bursting compared to P30 animals. Frequency-dependent burst firing was enhanced in P30, but not in P15 rats following KA-SE. The enhancement of bursting induced by KA-SE in more mature rats suggests that the frequency-dependent limitation of repetitive burst firing, which normally occurs in the subiculum, is compromised following SE. These changes could facilitate the initiation of spontaneous recurrent seizures or their spread from the hippocampus to other parts of the brain.

Highlights

  • Kainic acid (KA)- induced seizures are widely used as an experimental model of temporal lobe epilepsy, the most common surgically remediable drug-resistant epilepsy syndrome [1]

  • KA induced status epilepticus (KA-SE) results in a pattern of hippocampal neurodegeneration that resembles human hippocampal sclerosis [5, 7,8,9,10], but significant neuronal death following status epilepticus is not required for later spontaneous seizures to occur [11, 12]

  • Each group is denoted by an injection age and a recording age and a condition

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Summary

Introduction

Kainic acid (KA)- induced seizures are widely used as an experimental model of temporal lobe epilepsy, the most common surgically remediable drug-resistant epilepsy syndrome [1]. Status Epilepticus Increases Bursting in Subiculum convulsive seizure, include cell death, cell birth, axonal sprouting and electrophysiological changes [4, 5]. These processes contribute to epileptogenesis, but may be separate from the acute molecular and cellular changes caused by seizures [6]. KA induced status epilepticus (KA-SE) results in a pattern of hippocampal neurodegeneration that resembles human hippocampal sclerosis [5, 7,8,9,10], but significant neuronal death following status epilepticus is not required for later spontaneous seizures to occur [11, 12]

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