The role of cell death during neocortical neurogenesis and synaptogenesis: implications from a computational model for the rat and mouse
Abstract
We are quantitatively evaluating the acquisition of neocortical neurons through key stages of development including neurogenesis, migration, and synaptogenesis. Here we expand upon a previous computational model describing neocortical neurogenesis in the rat and mouse [Dev. Neurosci. 24 (2002) 467], to include the period of synaptogenesis (P0-P14) when programmed cell death (PCD) is known to play a major role in shaping the neocortex. We also quantitatively evaluate differing hypotheses on the role of cell death during neurogenesis. This new model construct allows prediction of acquisition of adult neuronal number in the rat and mouse neocortex from the beginning of neurogenesis through synaptogenesis. The mathematical model output is validated by independently derived stereologically determined neuron number estimates in the adult rat and mouse. Simulations suggest cell death during synaptogenesis reduces the neocortical neuronal population by 20-30%, while cell death of progenitor cells and newly formed neurons during neurogenesis may reduce output by as much as 24%. However, higher death rates during neurogenesis as suggested by some research would deplete the progenitor population, not allowing for the vast expansion that i...Continue Reading
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