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

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.