PMID- 20955719 OWN - NLM STAT- MEDLINE DCOM- 20120118 LR - 20211020 IS - 1873-7064 (Electronic) IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 60 IP - 7-8 DP - 2011 Jun TI - The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array. PG - 1142-53 LID - 10.1016/j.neuropharm.2010.10.007 [doi] AB - Epileptiform discharges recorded in the 4-aminopyridine (4-AP) in vitro epilepsy model are mediated by glutamatergic and GABAergic signaling. Using a 60-channel perforated multi-electrode array (pMEA) on corticohippocampal slices from 2 to 3 week old mice we recorded interictal- and ictal-like events. When glutamatergic transmission was blocked, interictal-like events no longer initiated in the hilus or CA3/CA1 pyramidal layers but originated from the dentate gyrus granule and molecular layers. Furthermore, frequencies of interictal-like events were reduced and durations were increased in these regions while cortical discharges were completely blocked. Following GABA(A) receptor blockade interictal-like events no longer propagated to the dentate gyrus while their frequency in CA3 increased; in addition, ictal-like cortical events became shorter while increasing in frequency. Lastly, drugs that affect tonic and synaptic GABAergic conductance modulated the frequency, duration, initiation and propagation of interictal-like events. These findings confirm and expand on previous studies indicating that multiple synaptic mechanisms contribute to synchronize neuronal network activity in forebrain structures. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. CI - Copyright (c) 2010 Elsevier Ltd. All rights reserved. FAU - Gonzalez-Sulser, Alfredo AU - Gonzalez-Sulser A AD - Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA. FAU - Wang, Jing AU - Wang J FAU - Motamedi, Gholam K AU - Motamedi GK FAU - Avoli, Massimo AU - Avoli M FAU - Vicini, Stefano AU - Vicini S FAU - Dzakpasu, Rhonda AU - Dzakpasu R LA - eng GR - R01 NS047700/NS/NINDS NIH HHS/United States GR - R01 NS047700-13/NS/NINDS NIH HHS/United States GR - CAPMC/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20101016 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Anticonvulsants) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Isoxazoles) RN - 0 (Piperazines) RN - 0 (Potassium Channel Blockers) RN - 0 (Quinoxalines) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 66016-70-4 (bicuculline methobromide) RN - 98Y1I8ZD4M (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) RN - BH3B64OKL9 (4-Aminopyridine) RN - K1M5RVL18S (gaboxadol) RN - Y37615DVKC (Bicuculline) SB - IM MH - 4-Aminopyridine/*toxicity MH - Animals MH - Anticonvulsants/pharmacology MH - Bicuculline/analogs & derivatives/pharmacology MH - CA3 Region, Hippocampal/drug effects MH - *Disease Models, Animal MH - Electrodes MH - Epilepsy/*chemically induced/drug therapy MH - GABA-A Receptor Antagonists/pharmacology MH - Hippocampus/drug effects MH - In Vitro Techniques MH - Isoxazoles/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Microarray Analysis/*methods MH - Motion Pictures MH - Piperazines/pharmacology MH - Potassium Channel Blockers/*toxicity MH - Quinoxalines/pharmacology MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors MH - Software MH - Somatosensory Cortex/drug effects MH - gamma-Aminobutyric Acid/metabolism PMC - PMC3032005 MID - NIHMS247528 EDAT- 2010/10/20 06:00 MHDA- 2012/01/19 06:00 PMCR- 2012/06/01 CRDT- 2010/10/20 06:00 PHST- 2010/07/27 00:00 [received] PHST- 2010/10/06 00:00 [revised] PHST- 2010/10/12 00:00 [accepted] PHST- 2010/10/20 06:00 [entrez] PHST- 2010/10/20 06:00 [pubmed] PHST- 2012/01/19 06:00 [medline] PHST- 2012/06/01 00:00 [pmc-release] AID - S0028-3908(10)00277-7 [pii] AID - 10.1016/j.neuropharm.2010.10.007 [doi] PST - ppublish SO - Neuropharmacology. 2011 Jun;60(7-8):1142-53. doi: 10.1016/j.neuropharm.2010.10.007. Epub 2010 Oct 16.