| 19674053 |
Yang XF, Schmidt BF, Rode DL, Rothman SM: Optical suppression of experimental seizures in rat brain slices. Epilepsia. 2010 Jan;51(1):127-35. Epub 2009 Aug 8.
PURPOSE: To determine if a small ultraviolet emitting diode (UV LED) could release sufficient gamma-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 microm. Seizure-like activity was induced by perfusing slices with extracellular medium lacking magnesium and containing 4-aminopyridine (4-AP; 100 microm). 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 degrees 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 GABA (A) 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. |
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