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Updated: May 10, 2026

Measuring Synaptic Vesicle Endocytosis in Cultured Hippocampal Neurons
Published on: September 4, 2017
Essential role of phosphoinositide metabolism in synaptic vesicle recycling
O Cremona1, G Di Paolo, M R Wenk
1Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Abstract:
Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates. We report here that synaptojanin 1-deficient mice exhibit neurological defects and die shortly after birth. In neurons of mutant animals, PI(4,5)P2 levels are increased, and clathrin-coated vesicles accumulate in the cytomatrix-rich area that surrounds the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation followed by delayed recovery. These results provide genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling.
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