Cerebral Cortex Advance Access originally published online on July 11, 2006
Cerebral Cortex 2007 17(6):1292-1306; doi:10.1093/cercor/bhl037
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Miniature Synaptic Currents Become Neurotoxic to Chronically Silenced Neurons
Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel
Address correspondence to email: menahem.segal{at}weizmann.ac.il.
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 12 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.
Key Words: AMPA receptors Ca2+ clearance cortical culture neurotoxicity tetrodotoxin
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