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.