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The Journal of Neuroscience, March 14, 2007, 27(11):3046-3056; doi:10.1523/JNEUROSCI.4415-06.2007

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 Previous Article

Cellular/Molecular
The Origin of Quantal Size Variation: Vesicular Glutamate Concentration Plays a Significant Role

Xin-Sheng Wu,¹ Lei Xue,¹ Raja Mohan,¹ Kenneth Paradiso,¹ Kevin D. Gillis,² and Ling-Gang Wu¹

¹National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, and ²Dalton Cardiovascular Research Center, University of Missouri–Columbia Research Park, Columbia, Missouri 65211

Correspondence should be addressed to Ling-Gang Wu, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 35 Convent Drive, Building 35, Room 2B-1012, Bethesda, MD 20892. Email: wul{at}ninds.nih.gov

Fusion of a single vesicle induces a quantal response, which is critical in determining synaptic strength. Quantal size varies at most synapses. Its underlying mechanisms are not well understood. Here, we examined five sources of variation: vesicular glutamate concentration ([Glu]_v), vesicle volume, ultrafast fusion pore closure, the postsynaptic receptor, and the location between release and the postsynaptic receptor cluster at glutamatergic, calyx of Held synapses. By averaging 2.66 million fusion events from 459 synapses, we resolved the capacitance jump evoked by single vesicle fusion. This capacitance jump, an indicator of vesicle volume, was independent of the amplitude of the miniature EPSC (mEPSC) recorded simultaneously at the same synapses. Thus, vesicle volume is not the main source of mEPSC variation. The capacitance jump was not followed by submillisecond endocytosis, excluding ultrafast endocytosis as a source of variation. Larger mEPSCs were increased to a lesser extent by presynaptic glutamate dialysis, and reduced to a lesser extent by -DGG (-D-glutamylglycine), a competitive AMPA receptor blocker, suggesting that a higher glutamate concentration in the synaptic cleft contributes to the large size of mEPSCs. Larger mEPSCs were not accompanied by briefer rise times, inconsistent with the prediction by, and thus arguing against, the scenario that larger mEPSCs are caused by a shorter distance between the release site and the postsynaptic receptor cluster. In summary, the different amplitudes of mEPSCs were mainly attributable to release of vesicles having similar volumes, but different glutamate amounts, suggesting that [Glu]_v is a main source of quantal size variation.

Key words: mEPSC; capacitance; glutamate; quantal content; synaptic; transmission

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Received Oct. 10, 2006; revised Feb. 15, 2007; accepted Feb. 16, 2007.

Correspondence should be addressed to Ling-Gang Wu, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 35 Convent Drive, Building 35, Room 2B-1012, Bethesda, MD 20892. Email: wul{at}ninds.nih.gov

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