Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-FoS expression

被引:462
作者
Baraban, SC
Taylor, MR
Castro, PA
Baier, H
机构
[1] Univ Calif San Francisco, Dept Neurol Surg, Epilepsy Res Lab, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA
基金
美国国家卫生研究院;
关键词
Danio rerio; epilepsy; extracellular; c-Fos; interictal; ictal;
D O I
10.1016/j.neuroscience.2004.11.031
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Upregulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:759 / 768
页数:10
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