Contribution of Ca2+ release channels to hippocampal synaptic plasticity and spatial memory: potential redox modulation

Antioxid Redox Signal. 2014 Aug 20;21(6):892-914. doi: 10.1089/ars.2013.5796. Epub 2014 Mar 11.


Significance: Memory is an essential human cognitive function. Consequently, to unravel the cellular and molecular mechanisms responsible for the synaptic plasticity events underlying memory formation, storage and loss represents a major challenge of present-day neuroscience.

Recent advances: This review article first describes the wide-ranging functions played by intracellular Ca2+ signals in the activity-dependent synaptic plasticity processes underlying hippocampal spatial memory, and next, it focuses on how the endoplasmic reticulum Ca2+ release channels, the ryanodine receptors, and the inositol 1,4,5-trisphosphate receptors contribute to these processes. We present a detailed examination of recent evidence supporting the key role played by Ca2+ release channels in synaptic plasticity, including structural plasticity, and the formation/consolidation of spatial memory in the hippocampus.

Critical issues: Changes in cellular oxidative state particularly affect the function of Ca2+ release channels and alter hippocampal synaptic plasticity and the associated memory processes. Emphasis is placed in this review on how defective Ca2+ release, presumably due to increased levels of reactive oxygen species, may cause the hippocampal functional defects that are associated to aging and Alzheimer's disease (AD).

Future directions: Additional studies should examine the precise molecular mechanisms by which Ca2+ release channels contribute to hippocampal synaptic plasticity and spatial memory formation/consolidation. Future studies should test whether redox-modified Ca2+ release channels contribute toward generating the intracellular Ca2+ signals required for sustained synaptic plasticity and hippocampal spatial memory, and whether loss of redox balance and oxidative stress, by altering Ca2+ release channel function, presumably contribute to the abnormal memory processes that occur during aging and AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging
  • Alzheimer Disease / metabolism
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Endoplasmic Reticulum / metabolism
  • Hippocampus / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Long-Term Potentiation
  • Long-Term Synaptic Depression
  • Neuronal Plasticity*
  • Neurons / metabolism
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Spatial Memory*


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Reactive Oxygen Species
  • Ryanodine Receptor Calcium Release Channel
  • Calcium