Doc2-mediated superpriming supports synaptic augmentation.

Abstract

Various forms of synaptic plasticity underlie aspects of learning and memory. Synaptic augmentation is a form of short-term plasticity characterized by synaptic enhancement that persists for seconds following specific patterns of stimulation. The mechanisms underlying this form of plasticity are unclear but are thought to involve residual presynaptic Ca²⁺ Here, we report that augmentation was reduced in cultured mouse hippocampal neurons lacking the Ca²⁺ sensor, Doc2; other forms of short-term enhancement were unaffected. Doc2 binds Ca²⁺ and munc13 and translocates to the plasma membrane to drive augmentation. The underlying mechanism was not associated with changes in readily releasable pool size or Ca²⁺ dynamics, but rather resulted from superpriming a subset of synaptic vesicles. Hence, Doc2 forms part of the Ca²⁺-sensing apparatus for synaptic augmentation via a mechanism that is molecularly distinct from other forms of short-term plasticity.