The Effect of Anti-Epileptic Drugs on 4- AP Induced Seizures in Rat Brain Slices

Abstract

Epilepsy is a neurological disorder that affects an estimated 50 million people, nearly one-third of whom do not have sufficient control over its symptoms. It is characterized by the onset of hypersynchronous neuronal activity known as seizures. The Netoff lab is focused on understanding the dynamics of epilepsy at the cellular and neural network levels. Our project focuses on how certain antiepileptic drugs alter the connections between neurons to prevent seizures. In this project, we performed extracellular recordings in rat hippocampal brain slices using a microscope and micropipette electrode setup. The brain slices rested in low-magnesium artificial cerebrospinal fluid containing 4-aminopyridine, a potassium ion channel blocker that causes seizures. Once seizures began, we introduced the anti-epileptic drug ethosuximide to the fluid and observed the effect on the seizures. We have seen that the amplitude of the seizure activity is much lower overall after the drug is applied. Often the drug also reduces the length and/or frequency of the seizures. When we stop adding the drug, the original seizures resume, creating a “wash-out” effect as the drug is no longer present. If we can discover the precise cause of seizure onset and the mechanisms by which anti-epileptic drugs affect it, we can develop more effective treatments for epileptic patients.