Calcium stores in the endoplasmic reticulum play important roles in a variety of mammalian cellular functions. However, the multitude of calcium-handling machineries in neurons, including voltage- and ligand-gated channels, calcium-binding proteins, pumps, and transporters, as well as the rapid mobility of calcium ions among different cellular compartments hampered the singling out of calcium stores as a pivotal player in synaptic plasticity. Despite these methodological obstacles, novel molecular and imaging tools afforded a rapid progress in deciphering the role of specific calcium stores in neuronal functions. In the present review, we will address several key issues related to the involvement of ryanodine receptors and the calcium entry channel Orai1 in dendritic spine development and plasticity as well as their derailing in neurodegenerative diseases.
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