Doc2-mediated superpriming supports synaptic augmentation

Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5605-E5613. doi: 10.1073/pnas.1802104115. Epub 2018 May 29.

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.

Keywords: Doc2; munc13; short-term plasticity; superpriming; synaptic augmentation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Cell Line
  • HEK293 Cells
  • Hippocampus / metabolism
  • Humans
  • Mice
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Rats
  • Synapses / metabolism*
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / metabolism*

Substances

  • Calcium-Binding Proteins
  • Calcium