Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

Philos Trans R Soc Lond B Biol Sci. 2017 Mar 5;372(1715):20160260. doi: 10.1098/rstb.2016.0260.


Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested.Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent super-resolution studies indicate that glutamatergic synapses are modular (module size 70-80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity.'

Keywords: CaMKII; long-term depression; long-term potentiation; metaplasticity; postsynaptic density; synaptic scaling.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Long-Term Potentiation
  • Long-Term Synaptic Depression
  • N-Methylaspartate / physiology
  • Neuronal Plasticity*
  • Receptors, AMPA / physiology
  • Synapses / physiology*


  • Receptors, AMPA
  • N-Methylaspartate