The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array.
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'.
Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.
Alfredo
A
Gonzalez-Sulser
Jing
J
Wang
Gholam K
GK
Motamedi
Massimo
M
Avoli
Stefano
S
Vicini
Rhonda
R
Dzakpasu
D015761:4-Aminopyridine / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000187:drug effects; D004195:Disease Models, Animal; D004566:Electrodes; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods*; D009040:Motion Pictures; D010879:Piperazines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000633:toxicity*; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012984:Software; D013003:Somatosensory Cortex / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D058787:GABA-A Receptor Antagonists; D007555:Isoxazoles; D010879:Piperazines; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005680:gamma-Aminobutyric Acid; C036615:bicuculline methobromide; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D015761:4-Aminopyridine; C015542:gaboxadol; D001640:Bicuculline