Pyramidal cells accumulate chloride at seizure onset

NEUROBIOLOGY OF DISEASE

卷:47

Article

Lillis, Kyle P.^2,3  Kramer, Mark A.⁴  Mertz, Jerome⁵  Staley, Kevin J.^2,3  White, John A.¹ 

[1] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA

[2] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[5] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA

关键词: Epilepsy;    Ictogenesis;    Chloride accumulation;    Ion imaging;    Calcium;    Seizure;    GABA;    Chloride transport;    Interneuron;    Targeted path scanning;   

DOI  :  10.1016/j.nbd.2012.05.016

来源: Elsevier

【 摘 要 】

Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABA(A) receptors or by hyperpolarizing the GABA(A) reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABA(A) receptor-mediated chloride influx shifts E-GABA to produce a positive feedback loop that contributes to the initiation of seizure activity. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free