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The Journal of Neuroscience, June 25, 2008, 28(26):6742-6749; doi:10.1523/JNEUROSCI.1082-08.2008

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Cellular/Molecular
Calcium Control of Endocytic Capacity at a CNS Synapse

J. Balaji,1 Moritz Armbruster,2 and Timothy A. Ryan1

1Department of Biochemistry, Weill Cornell Medical College, and 2David Rockefeller Graduate Program of The Rockefeller University, New York, New York 10065

Correspondence should be addressed to Timothy A. Ryan, Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, Room E-107, New York, NY 10065. Email: taryan{at}med.cornell.edu

The ability to recycle synaptic vesicles is a crucial property of nerve terminals that allows maintenance of synaptic transmission. Using high-sensitivity optical approaches at hippocampal nerve terminals in dissociated neurons in culture, we show that modulation of endocytosis can be achieved by expansion of the endocytic capacity. Our experiments indicate that the endocytic capacity, the maximum number of synaptic vesicles that can be internalized in parallel at individual synapses, is tightly controlled by intracellular calcium levels. Increasing levels of intracellular calcium, which occurs as firing frequency increases, significantly increases the endocytic capacity. At physiological temperature after 30 Hz firing, these synapses are capable of endocytosing at least ~28 vesicles in parallel, each with a time constant of ~6 s. This calcium-dependent control of endocytic capacity reveals a potentially useful adaptive response to high-frequency activity to increase endocytic rates under conditions of vesicle pool depletion.

Key words: endocytosis; synapse; pHluorin; recycling; calcium; vesicles

Received March 12, 2008; revised May 5, 2008; accepted May 20, 2008.

Correspondence should be addressed to Timothy A. Ryan, Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, Room E-107, New York, NY 10065. Email: taryan{at}med.cornell.edu






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