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Cerebral Cortex Advance Access published online on July 11, 2006

Cerebral Cortex, doi:10.1093/cercor/bhl037
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Article

Miniature Synaptic Currents Become Neurotoxic to Chronically Silenced Neurons

Ianai Fishbein 1 and Menahem Segal 1 *

1 Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel

* To whom correspondence should be addressed.
Menahem Segal, E-mail: menahem.segal{at}weizmann.ac.il


   Abstract

When deprived of spontaneous ongoing network activity by chronic exposure to tetrodotoxin (TTX), cultured cortical neurons retract their dendrites, lose dendritic spines, and degenerate over a period of 1-2 weeks. Electrophysiological properties of these slowly degenerating neurons prior to their death are normal, but they express very large miniature excitatory postsynaptic currents (mEPSCs). Chronic blockade of these mEPSCs by the alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6,7-Dinitroquinoxaline-2,3-dione (DNQX) had no effect of its own on cell survival, yet, paradoxically, it protected the TTX-silenced neurons from degenerating. TTX-treated neurons also exhibited deficient Ca2+ clearance mechanisms. Thus, upscaled mEPSCs are sufficient to trigger apoptotic processes in otherwise chronically silenced neurons.

Keywords: AMPA receptors; Ca2+ clearance; cortical culture; neurotoxicity; tetrodotoxin.
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