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Biophys J. 2011 Feb 2;100(3):593-601. doi: 10.1016/j.bpj.2010.12.3706.

Systematic heterogeneity of fractional vesicle pool sizes and release rates of hippocampal synapses.

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Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.
Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, Safat, Kuwait.
European Neuroscience Institute Göttingen, Deutsche Forschungsgemeinschaft Research Center for Molecular Physiology of the Brain/Excellence Cluster 171, Göttingen, Germany.
Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address:


Hippocampal neurons in tissue culture develop functional synapses that exhibit considerable variation in synaptic vesicle content (20-350 vesicles). We examined absolute and fractional parameters of synaptic vesicle exocytosis of individual synapses. Their correlation to vesicle content was determined by activity-dependent discharge of FM-styryl dyes. At high frequency stimulation (30 Hz), synapses with large recycling pools released higher amounts of dye, but showed a lower fractional release compared to synapses that contained fewer vesicles. This effect gradually vanished at lower frequencies when stimulation was triggered at 20 Hz and 10 Hz, respectively. Live-cell antibody staining with anti-synaptotagmin-1-cypHer 5, and overexpression of synaptopHluorin as well as photoconversion of FM 1-43 followed by electron microscopy, consolidated the findings obtained with FM-styryl dyes. We found that the readily releasable pool grew with a power function with a coefficient of 2/3, possibly indicating a synaptic volume/surface dependency. This observation could be explained by assigning the rate-limiting factor for vesicle exocytosis at high frequency stimulation to the available active zone surface that is proportionally smaller in synapses with larger volumes.

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