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  • Review Article
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Understanding calcium waves and sparks in central neurons

Nature Reviews Neuroscience volume 13, pages 157–168 (2012)Cite this article

Subjects

Key Points

  • Synaptic stimulation evokes postsynaptic intracellular calcium concentration ([Ca2+]i) changes via Ca2+ entry through ligand- and voltage-gated channels and via Ca2+ release from internal stores. Ca2+ release can be widespread and substantial, but often has no correlated change in membrane potential.

  • In many pyramidal neurons in the hippocampus, cortex and amygdala, Ca2+ release propagates as a wave in restricted regions of dendrites. The waves are evoked by metabotropic glutamate receptor (mGluR) mobilization of inositol trisphosphate (IP3) that regeneratively releases Ca2+ through IP3 receptors.

  • The range of wave propagation in dendrites depends on the number and location of synaptic inputs and the influence of neuromodulators.

  • Postsynaptic Ca2+ release and Ca2+ waves have been implicated in the modulation of membrane conductances and the induction of several forms of synaptic plasticity, including long-term potentiation and long-term depression. However, many of these results are controversial.

  • In addition to large-amplitude, widespread Ca2+ waves, localized, smaller amplitude, spontaneous Ca2+ release events have been detected in the soma, dendrites and presynaptic termini of many CNS neurons. These events resemble 'sparks' and 'puffs', which have been observed in many non-neuronal cell types.

  • The frequency of these events in dendrites can be modulated by changes in membrane potential in the subthreshold range, primarily by controlling Ca2+ entry through voltage-gated calcium channels. Their frequency can also be modulated by mGluR-mediated mobilization of IP3.

  • These localized events seem to contribute to the generation of large amplitude IP3-mediated Ca2+ waves. However, several of their properties implicate the involvement of ryanodine receptors, suggesting that they are more complex than IP3-mediated puffs.

  • Localized Ca2+ release events have been correlated with the generation of inhibitory postsynaptic currents at certain synapses, and these events locally increase Ca2+-activated K+ conductances in some cells. However, many of their functions remain to be determined.

Abstract

All cells use changes in intracellular calcium concentration ([Ca2+]i) to regulate cell signalling events. In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and widespread Ca2+ signals. [Ca2+]i changes that are generated by Ca2+ entry through voltage- and ligand-gated channels are the best characterized. In addition, the release of Ca2+ from intracellular stores can result in increased [Ca2+]i; the signals that trigger this release have been less well-studied, in part because they are not usually associated with specific changes in membrane potential. However, recent experiments have revealed dramatic widespread Ca2+ waves and localized spark-like events, particularly in dendrites. Here we review emerging data on the nature of these signals and their functions.

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Figure 1: Model of regenerative Ca2+ release and wave propagation.
Figure 2: Synaptically activated Ca2+ waves in a neocortical pyramidal neuron.
Figure 3: Model of the distribution of molecules that affect the generation of Ca2+ waves and sparks in a hippocampal pyramidal neuron.
Figure 4: Spontaneous Ca2+ release events occur in localized regions of the dendrites of hippocampal pyramidal neurons.

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Acknowledgements

I thank members of my laboratory for many insightful discussions and J. Lisman and P. Sah for comments on an earlier version of this manuscript. W.N.R. is supported by a grant from the US National Institutes of Health (NS-16295).

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  1. New York Medical College, Valhalla, 10595, New York, USA

    William N. Ross

  2. Marine Biological Laboratory, Woods Hole, 02543, Massachusetts, USA

    William N. Ross

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Supplementary information

Supplementary Information S1 (movie)

Synaptically activated Ca2+ wave in the dendrites of a CA1 pyramidal neuron. (AVI 7338 kb)

Supplementary Information S1 (movie)

Synaptically activated Ca2+ wave in the dendrites of a CA1 pyramidal neuron. (PDF 93 kb)

Supplementary Information S2 (movie)

Spontaneous localized Ca2+ release events along the main apical dendrites of a CA1 pyramidal neuron. (MPG 2349 kb)

Supplementary Information S2 (movie)

Spontaneous localized Ca2+ release events along the main apical dendrites of a CA1 pyramidal neuron. (PDF 96 kb)

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Glossary

NMDA spikes

Short, sharp increases in NMDA receptor current that result from regenerative mechanisms in which the nonlinear component is the voltage dependence of the NMDA receptor. These spikes usually occur in dendrites, leading to large increases in intracellular calcium concentration but relatively small changes in somatic membrane potential.

Coincidence detector

A term derived from electrical engineering that refers to the output of a circuit that is dependent on the simultaneous arrival of two (or more) inputs. The inositol trisphosphate receptor (IP3R) is a coincidence detector for Ca2+ and IP3.

Hebbian plasticity

A form of neuronal plasticity in which a change in a property (often synaptic strength) results from the simultaneous activation (sometimes repetitively) of presynaptic and postsynaptic cells.

'Up' and 'down' states

Persistent depolarizations and hyperpolarizations in neurons that can differ by 10 to 20mV. They are primarily observed in cortical neurons and are thought to be driven by network activity.

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Ross, W. Understanding calcium waves and sparks in central neurons. Nat Rev Neurosci 13, 157–168 (2012). https://doi.org/10.1038/nrn3168

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