Abstract

Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail.

Highlights

  • It is widely accepted that in mammals, including humans, newly born neurons are continuously generated and incorporated into the functional neural network of the adult brain (McKay, 1997; Gage, 2000; Temple, 2001; Ming and Song, 2005; Imayoshi et al, 2008, 2009)

  • Nestin is expressed in the subventricular zone (SVZ) and subgranular zone (SGZ) of the adult brain (Doetsch et al, 1997), and in Nestin-CreER transgenic mice, neural stem cells (NSCs) and transit-amplifying cells express CreER

  • CAG promoter transgenic mice are able to induce higher levels of reporter expression than the Rosa26 promoter in most cells, the promoter activity is silenced in some cells and not completely ubiquitous probably due to unfavorable chromatin configurations

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Summary

Introduction

It is widely accepted that in mammals, including humans, newly born neurons are continuously generated and incorporated into the functional neural network of the adult brain (McKay, 1997; Gage, 2000; Temple, 2001; Ming and Song, 2005; Imayoshi et al, 2008, 2009). Born neurons are incorporated into the functional neural networks of the OB and the DG, suggesting a significant impact of adult neurogenesis on neural circuit plasticity, and various brain functions, including learning and memory (van Praag et al, 2002; Carleton et al, 2003; Kee et al 2007; Adam and Mizrahi, 2010; Deng et al, 2010; Lazarini and Lledo, 2011) Neurogenesis outside these two regions appears to be extremely limited in the intact adult mammalian central nervous system (CNS). We discuss the experimental approaches to visualize newly generated neurons and manipulate neurogenesis in the adult brain, especially focusing on genetic methods

Visualizing and manipulating newborn neurons
DCX promoter
Tau locus
Conclusion
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