Nano-organization of synaptic calcium signaling

Recent studies suggest an exquisite structural nano-organization within single synapses, where sites of evoked fusion - marked by clustering of synaptic vesicles, active zone proteins and voltage-gated calcium channels - are directly juxtaposed to postsynaptic receptor clusters within nanocolumns. This direct nanometer scale alignment between presynaptic fusion apparatus and postsynaptic receptors is thought to ensure the fidelity of synaptic signaling and possibly allow multiple distinct signals to occur without interference from each other within a single active zone. The functional specificity of this organization is made possible by the inherent nano-organization of calcium signals, where all the different calcium sources such as voltage-gated calcium channels, intracellular stores and store-operated calcium entry have dedicated local targets within their nanodomain to ensure precision of action. Here, we discuss synaptic nano-organization from the perspective of calcium signals, where some of the principal findings from early work in the 1980s continue to inspire current studies that exploit new genetic tools and super-resolution imaging technologies.