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Abstract

Synaptic transmission relies on the continual exocytosis and recycling of synaptic vesicles. Aged vesicle proteins are prevented from recycling and are eventually degraded. This implies that active synapses would lose
vesicles and vesicle-associated proteins over time, unless the supply correlates to activity, to balance the
losses. To test this hypothesis, we first model the quantitative relation between presynaptic spike rate and
vesicle turnover. The model predicts that the vesicle supply needs to increase with the spike rate. To follow
up this prediction, we measure protein turnover in individual synapses of cultured hippocampal neurons by
combining nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence microscopy. We find
that turnover correlates with activity at the single-synapse level, but not with other parameters such as the
abundance of synaptic vesicles or postsynaptic density proteins. We therefore suggest that the supply of
newly synthesized proteins to synapses is closely connected to synaptic activity.