Models of drug-induced epileptiform synchronization in vitro.
Models of epileptiform activity in vitro have many advantages for recording and experimental manipulation. Neural tissues can be maintained in vitro for hours, and in neuronal or organotypic slice cultures for several weeks. A variety of drugs and other agents increase activity in these in vitro conditions, in many cases resulting in epileptiform activity, thus providing a direct model of symptomatic seizures. We review these preparations and the experimental manipulations used to induce epileptiform activity. The most common of drugs used are GABAA receptor antagonists and potassium channel blockers (notably 4-aminopyridine). Muscarinic agents also can induce epileptiform synchronization in vitro, and include potassium channel inhibition amongst their cellular actions. Manipulations of extracellular ions are reviewed in another paper in this special issue, as are ex vivo slices prepared from chronically epileptic animals and from people with epilepsy. More complex slices including extensive networks and/or several connected brain structures can provide insights into the dynamics of long range connections during epileptic activity. Visualization of slices also provides opportunities for identification of living neurons and for optical recording/stimulation and manipulation. Overall, the analysis of the epileptiform activity induced in brain tissue in vitro has played a major role in advancing our understanding of the cellular and network mechanisms of epileptiform synchronization, and it is expected to continue to do so in future.
Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montréal, QC, Canada H3A 2B4; Department of Experimental Medicine, Facoltà di Medicina e Odontoiatria, Sapienza University of Rome, Roma 00185, Italy. Electronic address: massimo.avoli@mcgill.ca.
Massimo
M
Avoli
Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
John G R
JG
Jefferys
D000818:Animals; D002478:Cells, Cultured; D018678:Cholinergic Agents; D003344:Cortical Synchronization / Q000187:drug effects*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D018756:GABA Antagonists; D006801:Humans; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009924:Organ Culture Techniques / Q000379:methods; D026902:Potassium Channel Blockers
D018678:Cholinergic Agents; D018756:GABA Antagonists; D026902:Potassium Channel Blockers
Animal models in vitro; Epileptiform synchronization; GABA(A) receptor antagonists; K(+) channel blockers