The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array

NEUROPHARMACOLOGY

卷:60

Article

Gonzalez-Sulser, Alfredo²  Wang, Jing^3,4,10  Motamedi, Gholam K.^2,5  Avoli, Massimo^6,7,8,9  Vicini, Stefano^1,2  Dzakpasu, Rhonda^2,3,4 

[1] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA

[2] Georgetown Univ, Interdisciplinary Program Neurosci, Washington, DC 20007 USA

[3] Georgetown Univ, Dept Phys, Washington, DC 20007 USA

[4] Georgetown Univ, Dept Pharmacol, Washington, DC 20007 USA

[5] Georgetown Univ, Dept Neurol, Washington, DC 20007 USA

[6] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada

[7] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada

[8] McGill Univ, Dept Physiol, Montreal, PQ H3A 2B4, Canada

[9] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy

[10] Xi An Jiao Tong Univ, Dept Instrument Sci & Technol, Xian 710049, Peoples R China

关键词: Seizures;    Hippocampus;    4-Aminopyridine;    Local field potentials;    GABA;   

DOI  :  10.1016/j.neuropharm.2010.10.007

来源: Elsevier

【 摘 要 】

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'. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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