What is the extracellular calcium concentration within brain synapses? An Editorial for 'Ionized calcium in human cerebrospinal fluid and its influence on intrinsic and synaptic excitability of hippocampal pyramidal neurons in the rat' on page 452.

Calcium (Ca2+) is essential for the normal functioning of the brain: Ca2+ inflow into synaptic compartments is a major trigger of neurotransmitter release and of long-term plastic changes of synaptic efficiency. Ca2+ influx depends on the gradient for this ion across the plasma membrane, and slight fluctuations of extracellular Ca2+ concentration have significant impact on axonal excitability, synaptic transmission, and plasticity. The work by Forsberg et al. reports a concentration of physiologically active Ca2+ in human cerebrospinal fluid (CSF) that is half of that normally used in artificial CSF in electrophysiological brain slice experiments. By studying the impact of such difference of extracellular Ca2+ concentration, the authors reported significant differences in terms of neuronal excitability and long-term potentiation in rat hippocampal slices. We now discuss these new findings in the context of the spatial organization of synapses, on the role of astrocytes in filtering the synaptic content and on the complexity of plasticity in a broad context of metaplastic modifications of synaptic efficiency.