| Autor: |
Dugladze, Tamar, Maziashvili, Nino, Börgers, Christoph, Gurgenidze, Shalva, Häussler, Ute, Winkelmann, Aline, Haas, Carola A., Meier, Jochen C., Vida, Imre, Kopell, Nancy J., Gloveli, Tengis |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 9/10/2013, Vol. 110 Issue 37, p15073-15078, 6p |
| Abstrakt: |
GABAB receptors (GABABRs) mediate slow inhibitory effects on neuronal excitability and synaptic transmission in the brain. However, the GABABR agonist baclofen can also promote excitability and seizure generation in human patients and animals models. Here we show that baclofen has concentration-dependent effects on the hippocampal network in a mouse model of mesial temporal lobe epilepsy. Application of baclofen at a high dose (10 mg/kg i.p.) reduced the power of γ oscillations and the frequency of pathological discharges in the Cornu Ammonis area 3 (CA3) area of freely moving epileptic mice. Unexpectedly, at a lower dose (1 mg/kg), baclofen markedly increased γ activity accompanied by a higher incidence of pathological discharges. Intracellular recordings from CA3 pyramidal cells in vitro further revealed that, although at a high concentration (10 µM), baclofen invariably resulted in hyperpolarization, at low concentrations (0.5 µM), the drug had divergent effects, producing depolarization and an increase in firing frequency in epileptic but not control mice. These excitatory effects were mediated by the selective muting of inhibitory cholecystokinin-positive basket cells (CCK+ BCs), through enhanced inhibition of GABA release via presynaptic GABABRs. We conclude that cell type–specific up-regulation of GABABR-mediated autoinhibition in CCK+ BCs promotes aberrant high frequency oscillations and hyperexcitability in hippocampal networks of chronic epileptic mice. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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