Calcium: A Fundamental Player in Brain Development

Calcium Waves

During the stage of neurogenesis in the embryonic brain, Ca2+ plays an orchestrating role in the function and behavior of neural-stem/progenitor cells (NSPCs). Owens and Kriegstein [1] r eport in the developing rat cortex 3 groups of NSPCs  based on the patterns of spontaneous intracellular Ca2+ waves having as epicenter the cell soma. The authors note 1), single cells generating independent Ca2+ waves, 2),  pairs of cells undergoing synchronous Ca2+ fluctuations and last, 3) groups of adjacent cells undergoing coordinated Ca2+bursts. Weissman et. al. [2], report that radial glial Ca2+ waves depend on connexin hemichannels, P2Y1 ATP receptors, and intracellular IP3-mediated Ca2+ release. In addition, inhibition of  Ca2+ propagation results in impairment of proliferation. The latter is illustrated in the figure below (from [2]). The pattern, frequency and type of Ca2+ waves observed in precursor cells and differentiating neurons differs. Accordingly, NSPCs have lower frequency waves which are generated by intracellular Ca2+ release and are not dependent on neurotransmitter release [1,2]. Contrary, differentiating cells have increased frequency and duration of Ca2+ bursts resulting from voltage-dependent  L-type Ca2+ channel activation [3]. Also, intracellular Ca2+stores in differentiating neurons have ryanodine and caffeine sensitivity and baseline cytosolic Ca2+ levels  depend on Na+– Ca2+ exchange activity.

Calcium Waves "Push" NSPCs through the Cell Cycle

 

References

[1]  Owens, DF and Kriegstein, AR (1998) Patterns of Intracellular Calcium Fluctuation in Precursor Cells of the Neocortical Ventricular Zone. J.Neurosc 18(14):5374-5388

[2] Weissman TA, Riquelme PA,  Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661.

[3] Maric D, Maric I, Barker JL (2000) Developmental changes in cell calcium homeostasis during neurogenesis of the embryonic rat cerebral cortex. Cereb Cortex10:561–573.

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