Superpriming of synaptic vesicles as a common basis for intersynapse variability and modulation of synaptic strength

Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4548-57. doi: 10.1073/pnas.1606383113. Epub 2016 Jul 18.

Abstract

Glutamatergic synapses show large variations in strength and short-term plasticity (STP). We show here that synapses displaying an increased strength either after posttetanic potentiation (PTP) or through activation of the phospholipase-C-diacylglycerol pathway share characteristic properties with intrinsically strong synapses, such as (i) pronounced short-term depression (STD) during high-frequency stimulation; (ii) a conversion of that STD into a sequence of facilitation followed by STD after a few conditioning stimuli at low frequency; (iii) an equalizing effect of such conditioning stimulation, which reduces differences among synapses and abolishes potentiation; and (iv) a requirement of long periods of rest for reconstitution of the original STP pattern. These phenomena are quantitatively described by assuming that a small fraction of "superprimed" synaptic vesicles are in a state of elevated release probability (p ∼ 0.5). This fraction is variable in size among synapses (typically about 30%), but increases after application of phorbol ester or during PTP. The majority of vesicles, released during repetitive stimulation, have low release probability (p ∼ 0.1), are relatively uniform in number across synapses, and are rapidly recruited. In contrast, superprimed vesicles need several seconds to be regenerated. They mediate enhanced synaptic strength at the onset of burst-like activity, the impact of which is subject to modulation by slow modulatory transmitter systems.

Keywords: Munc13; calyx of Held; phorbol ester; posttetanic potentiation; short-term plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • Glutamic Acid / metabolism
  • Male
  • Models, Neurological
  • Neuronal Plasticity / physiology
  • Rats, Wistar
  • Signal Transduction / physiology
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / physiology*

Substances

  • Glutamic Acid