Optical suppression of experimental seizures in rat brain slices

Abstract

Purpose: To determine if a small ultraviolet emitting diode (UV LED) could release sufficient γ-aminobutyric acid (GABA) from a caged precursor to suppress paroxysmal activity in rat brain slices. Methods: Electrophysiologic recordings were obtained from rat brain slices bathed with caged GABA: 4-[[(2H-benzopyran-2-one-7-amino-4-methoxy)carbonyl]amino]butanoic acid (BC204), at concentrations between 3 and 30 μm. Seizure-like activity was induced by perfusing slices with extracellular medium lacking magnesium and containing 4-aminopyridine (4-AP; 100 μm). A small, high-power UV LED was used to uncage BC204 and determine whether an increase in ambient GABA could alter normal or paroxysmal activity in the slice. Results: UV LED illumination, in the absence of BC204, had no effect on CA1 population spikes or seizure-like activity. The light did induce a small temperature elevation (<0.15°C) over the current intensities and exposure durations used in these experiments. In the presence of BC204, UV light decreased the CA1 population spike and seizure-like activity. The BC204 effect can be best accounted for by release of GABA: The reduction of population spikes and seizure-like activity was blocked by the GABA antagonist picrotoxin, and BC204 illumination produced a membrane polarization that reversed at the expected potential for GABAA receptors. Discussion: These experiments establish that illumination of a low concentration of caged GABA with a tiny UV LED can release sufficient GABA to attenuate seizure-like activity in brain slices. Because our seizure model is very severe, it is probable that this technique would have a robust effect in human focal epilepsy. © 2009 International League Against Epilepsy.