Birth and death of neurons in the developing and mature mammalian brain

Abstract

Neuron birth and death are two contradictory processes, yet serving the same purpose of the formation of the brain. They coexist during brain development, when cytoarchitecture and synaptic contacts are progressively established. It is the highly programmed interplay between these two processes that results in the making of a mature, complex-wired, functional brain. Neurogenesis is the process that begins with the birth of naïve new neurons, which are gradually specified to their prospective cell fate, translocate through migratory streams to the brain area they are destined for and terminally differentiate into mature neurons that integrate into neuronal networks with sophisticated functions. This is an ongoing process until adulthood, when it mediates brain neuroplasticity. Neuron death is the process through which the fine sculpting and modeling of the brain is achieved. It serves to adjust final neuron numbers, exerting quality control on neurons that birth has generated or overproduced. It additionally corrects early wiring and performs systems matching by negatively selecting neurons that fail to gain neurotransmitter-mediated neuronal activity or receive neurotrophic support for maintenance and function. It is also a means by which organizing centers and transient structures are removed early in morphogenesis. Both processes are evolutionary conserved, genetically programmed and orchestrated by the same signaling factors regulating the cell cycle, neuronal activity/neurotransmitter action and neurotrophic support. This review summarizes and highlights recent knowledge on birth and death of neurons, the two mutually dependent contributors to the formation of the highly evolved mammalian brain.