thesis

Spatial cognition during the active avoidance task: The role of the prefrontal cortex and preempting impairment following febrile status epilepticus

Abstract

The active place avoidance task is a dynamic spatial cognition task that has been used to study spatial memory impairment in animal models of epilepsy in order to better understand how prolonged early-life seizures affect cognition. To determine whether the prefrontal cortex is necessary for this task, the performance of adult male rats (n = 3) was assessed before and after bilateral injections of muscimol or PBS in the medial prefrontal cortex (mPFC). Both muscimol and PBS impaired task performance, though only muscimol altered hippocampal oscillations in the theta and gamma ranges. Due to small sample size and potential confounds, these results do not strongly indicate the necessity of the mPFC in this task. However, muscimol had more profound effects on behavior and network activity than PBS, suggesting that with a bigger sample size the involvement of the mPFC could be demonstrated. In addition, the role of neuron-restrictive silencer factor (NRSF), a protein that is overexpressed after prolonged seizures, was investigated with regard to prolonged seizure-related cognitive deficits. Rats induced with febrile status epilepticus (FSE) and given intracerebral injections of neuron-restrictive silencer element (NRSE), which has been shown to decrease NRSF levels, performed as well as controls, measured in terms of shock zone entrances, shocks, and time spent opposite the shock zone. Untreated FSE rats were impaired in each of these measurements. These results provide strong evidence that NRSF overexpression mediates FSE-induced cognitive impairment

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