The role of the endoplasmic reticulum Ca2+ store in the plasticity of central neurons

The smooth endoplasmic reticulum (SER) is a well-characterized buffer and source of Ca2+ in both axonal and dendritic compartments of neurons. Ca2+ release from the SER can be evoked by stimulation of the ryanodine receptor or the inositol (1,4,5)-trisphosphate [Ins(1,4,5)P-3] receptor. Both receptors can couple to the activation of neurotransmitter-gated receptors and voltage-gated Ca2+ channels on the plasma membrane, thus enabling the SER to discriminate between different types of neuronal activity. In axonal terminals, Ca2+-induced Ca2+ release (CICR) mediates spontaneous, evoked and facilitated neurotransmission. Store release might also regulate the mobilization and recycling of synaptic vesicles. In the dendritic compartment, the distribution of Ins(1,4,5)P-3 receptors and ryanodine receptors influences the intracellular encoding of neuronal activity. Thus, the functionality of the Ca2+ store can affect both the polarity and the spatial extent of Ca2+-dependent shifts in synaptic efficacy. In hippocampal neurons, for example, CICR in the spine heads underlies homosynaptic plasticity, whereas heterosynaptic plasticity is mediated by Ins(1,4,5)P-3-dependent Ca2+ signalling. Purkinje neurons primarily express Ins(1,4,5)P-3 receptors in the spine heads, and long-term depression of synaptic efficacy is crucially dependent on Ins(1,4,5)P-3.