An in vitro seizure model from human hippocampal slices using multi-electrode arrays

Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Charles Y Liu; Christianne N Heck; David Millett; Theodore W Berger

doi:10.1016/j.jneumeth.2014.09.010

An in vitro seizure model from human hippocampal slices using multi-electrode arrays

J Neurosci Methods. 2015 Apr 15:244:154-63. doi: 10.1016/j.jneumeth.2014.09.010. Epub 2014 Sep 22.

Authors

Min-Chi Hsiao¹, Pen-Ning Yu², Dong Song³, Charles Y Liu⁴, Christianne N Heck⁵, David Millett⁶, Theodore W Berger⁷

Affiliations

¹ Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: mhsiao@usc.edu.
² Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: penning@usc.edu.
³ Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: dsong@usc.edu.
⁴ Department of Neurological Surgery and Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Department of Biomedical Engineering, and Rancho Los Amigos National Rehabilitation Center, USA. Electronic address: cliu@med.usc.edu.
⁵ Department of Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Los Angeles, CA 90033, USA. Electronic address: check@med.usc.edu.
⁶ Department of Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Los Angeles, CA 90033, USA; Rancho Los Amigos National Rehabilitation Center, Downey, CA 90242, USA. Electronic address: millett@med.usc.edu.
⁷ Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: berger@usc.edu.

PMID: 25244953
DOI: 10.1016/j.jneumeth.2014.09.010

Abstract

Temporal lobe epilepsy is a neurological condition marked by seizures, typically accompanied by large amplitude synchronous electrophysiological discharges, affecting a variety of mental and physical functions. The neurobiological mechanisms responsible for the onset and termination of seizures are still unclear. While pharmacological therapies can suppress the symptoms of seizures, typically 30% of patients do not respond well to drug control. Unilateral temporal lobectomy, a procedure in which a substantial part of the hippocampal formation and surrounding tissue is removed, is a common surgical treatment for medically refractory epilepsy. In this study, we have developed an in vitro model of epilepsy using human hippocampal slices resected from patients suffering from intractable mesial temporal lobe epilepsy. We show that using a planar multi-electrode array system, spatio-temporal inter-ictal like activity can be consistently recorded in high-potassium (8 mM), low-magnesium (0.25 mM) artificial cerebral spinal fluid with 4-aminopyridine (100 μM) added. The induced epileptiform discharges can be recorded in different subregions of the hippocampus, including dentate, CA1 and subiculum. This new paradigm will allow the study of seizure generation in different subregions of hippocampus simultaneously, as well as propagation of seizure activity throughout the intrinsic circuitry of hippocampus. This experimental model also should provide insights into seizure control and prevention, while providing a platform to develop novel, anti-seizure therapeutics.

Keywords: Human hippocampal slices; In vitro seizure model; Mesial temporal lobe epilepsy; Multi-electrode arrays.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

4-Aminopyridine / pharmacology
Action Potentials / drug effects
Action Potentials / physiology*
Dose-Response Relationship, Drug
Electrodes*
Hippocampus / physiopathology*
Humans
In Vitro Techniques* / instrumentation
In Vitro Techniques* / methods
Potassium / pharmacology
Potassium Channel Blockers / pharmacology
Seizures / pathology*

Substances

Potassium Channel Blockers
4-Aminopyridine
Potassium