Time Is on Our Side

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Science  21 Mar 2008:
Vol. 319, Issue 5870, pp. 1591
DOI: 10.1126/science.319.5870.1591c

The cerebellum is a highly ordered brain structure, with the axons of small numerous granule cells projecting to the dendritic tree of large Purkinje cells in a stereotyped way. All of the daughters of individual granule cell precursors connect to the same horizontal layer within the Purkinje cell dendrites, although their cell bodies are not grouped together. How does this structure assemble so precisely?

By tracing the lineal descent and migration of granule cells with a method that visualizes their axonal and dendritic projections, Espinosa and Luo have revealed that it occurs by application of a straightforward principle. All of the offspring of each precursor granule cell exit the cell cycle within a narrow time window and synchronously connect their axons to the top surface of the layer containing the Purkinje cell dendrites. Each clonally related family of granule cells takes its turn to differentiate and connect to the Purkinje cell dendrites, resulting in their axons stacking in the dendrites in chronological order from deep to superficial. This sequential maturation of granule cells coincides with the ordered arrival of their mossy fiber inputs, which arrive from other brain areas at different times. Inputs from each brain region would therefore target a different region of the Purkinje cell dendritic tree and so have a distinct influence on computation. Thus, the developing brain uses the simple principle of temporal sequencing to assemble a precise and complex computational machine. — KK

J. Neurosci. 28, 2301 (2008).

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