5 The Use of Reporter Mouse Lines to Study Adult Neurogenesis

A long-standing problem in the field of adult neurogenesis has been the need to identify newborn neurons and their precursors within a much larger population of preexisting mature neurons and glia. If these nascent cells could be identified, it would be possible to visualize and enumerate such cells in vivo, to access them for electrophysiological and molecular studies, to identify their connections in the neuronal networks, and to alter their activity and function. Several strategies have been developed to solve this problem of finding the proverbial needle in a haystack. Methods such as labeling with thymidine analogs, phenotypic analysis based on the expression of developmental markers, and retro- and lentiviral labeling have each had an important role in advancing our understanding of the proliferation and maturation of newborn neurons in the adult brain. As with all methods, these techniques have advantages and limits that demarcate their appropriate application. In this review, we focus on genetic approaches to studying adult mammalian neurogenesis, describing reporter lines of transgenic mice and summarizing recent advances that employ these emerging technologies. The general strategy of these genetic approaches is to drive the expression of “live” markers such as green fluorescent protein (GFP) in a defined population of neurons, neuronal progenitors, or stem cells. Cytoplasmic expression of fluorescent proteins (FPs) allows the full morphology of labeled cells to be visualized, whereas nuclear expression of such proteins facilitates cell enumeration. FP expression also allows labeled cells to be identified and accessed in live animals and in acute...