Scientific Understanding of Consciousness
Neural Stem Cells can produce Neurogenesis in Adult Brain
Science 29 March 2013: 1534-1535
Neura l Stem Cells, Excited
Jenny Hsieh and Jay W. Schneider
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Although the brain is generally considered a terminally differentiated organ, new nerve cells are made every day through a process called “adult neurogenesis,” which occurs in specialized regions like the hippocampal dentate gyrus. Stem cells in the brain sample electrical signals (activity) from neighboring neurons, deciding which genes to express and which signaling pathways to launch toward developing their own neuronal identity.
Cultured neural stem/progenitor cells isolated from rodent hippocampus can respond to external neural activity and differentiate into neurons. This activity-dependent neurogenesis requires Ca2+ channels and receptors for the neurotransmitter N-methyl-d-aspartate (NMDA) on proliferating stem/progenitor cells, and hence is called “excitation-neurogenesis coupling.” Once proliferating stem/progenitor cells differentiate into slightly later stages of neuroblasts and immature neurons, excitation signaling in the form of GABA is also necessary to drive the functional integration of newborn neurons.
Depolarization causes an increase in intracellular Ca2+ concentration similar to that evoked in cultured neural stem/progenitor cells. This excitation signal is relayed to the genome wherein the transcription factor NeuroD is rapidly activated to promote neurogenesis.
These studies highlight the importance of excitation-neurogenesis coupling in the stepwise differentiation and maturation of adult neural stem/progenitor cells in the mammalian brain. Neural stem cells in the brain called radial glial-like (RGL) cells can respond to neural activity. RGLs maintain the adult neural stem cell pool in the hippocampus by remaining quiescent; the maintenance and activation of RGLs is dynamically controlled by experience and aging.
Generally, stem cells deflect or reject environmental signals that might trigger differentiation and the loss of stemness. In adult tissues and organs, like the brain, stem cells already possess sophisticated receptor systems to immediately sense environmental changes. However, instead of initiating cellular specialization, which would possibly irreversibly deplete the stem cell pool, these receptor systems help stem cells decide how many (or how few) progeny cells to produce. It may be that the neurogenesis response of stem/progenitor cells to activity is an adaptive mechanism to maintain regional homeostasis.
The adult brain continues to develop under the influence of electrical activity, such that similar to mechanical stretch regulation of muscle growth, behavior and circuit activity control adult neurogenesis. A potential drawback of excitable stem cells is inappropriate activation after pathological forms of activity, such as seizures. Understanding how electrical activity controls adult neural stem cell properties and neurogenesis is likely to provide mechanistic insight into neural circuit function and new tools for mapping human brain connections.
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