title: Forebrain electrophysiological recording in larval zebrafish.
abstract: Epilepsy affects nearly 3 million people in the United States and up to 50 million people worldwide. Defined as the occurrence of spontaneous unprovoked seizures, epilepsy can be acquired as a result of an insult to the brain or a genetic mutation. Efforts to model seizures in animals have primarily utilized acquired insults (convulsant drugs, stimulation or brain injury) and genetic manipulations (antisense knockdown, homologous recombination or transgenesis) in rodents. Zebrafish are a vertebrate model system that could provide a valuable alternative to rodent-based epilepsy research. Zebrafish are used extensively in the study of vertebrate genetics or development, exhibit a high degree of genetic similarity to mammals and express homologs for ~85% of known human single-gene epilepsy mutations. Because of their small size (4-6 mm in length), zebrafish larvae can be maintained in fluid volumes as low as 100 μl during early development and arrayed in multi-well plates. Reagents can be added directly to the solution in which embryos develop, simplifying drug administration and enabling rapid in vivo screening of test compounds. Synthetic oligonucleotides (morpholinos), mutagenesis, zinc finger nuclease and transgenic approaches can be used to rapidly generate gene knockdown or mutation in zebrafish. These properties afford zebrafish studies an unprecedented statistical power analysis advantage over rodents in the study of neurological disorders such as epilepsy. Because the "gold standard" for epilepsy research is to monitor and analyze the abnormal electrical discharges that originate in a central brain structure (i.e., seizures), a method to efficiently record brain activity in larval zebrafish is described here. This method is an adaptation of conventional extracellular recording techniques and allows for stable long-term monitoring of brain activity in intact zebrafish larvae. Sample recordings are shown for acute seizures induced by bath application of convulsant drugs and spontaneous seizures recorded in a genetically modified fish.
authors: Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, USA. scott.baraban@ucsf.edu
authors: Scott C
authors: SC
authors: Baraban
mesh_terms: D000818:Animals; D055724:Electrophysiological Phenomena; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods*; D007814:Larva; D008839:Microelectrodes; D016548:Prosencephalon / Q000502:physiology*; D015027:Zebrafish
references: Epilepsia. 2007 Jun;48(6):1151-7
references: 17521353
references: Front Biosci. 2002 Jun 01;7:d1439-53
references: 12045008
references: Development. 1996 Dec;123:241-54
references: 9007244
references: J Neurosci Methods. 2006 Jul 15;155(1):39-48
references: 16564574
references: Nat Genet. 2000 Oct;26(2):216-20
references: 11017081
references: Rev Neurosci. 2011;22(1):49-62
references: 21615261
references: Prog Neurobiol. 2011 Feb;93(2):231-43
references: 21130139
references: Epilepsia. 2010 Apr;51(4):592-601
references: 19780794
references: J Vis Exp. 2009 Mar 09;(25):
references: 19274045
references: Development. 2011 Oct;138(20):4555-64
references: 21937602
references: Methods Mol Biol. 2009;561:41-63
references: 19504063
references: PLoS One. 2012;7(5):e36690
references: 22615792
references: Neuroscience. 2005;131(3):759-68
references: 15730879