A comparative framework for understanding the biological principles of adult neurogenesis

Abstract

Adult neurogenesis has been identified in all vertebrate species examined thus far. However, an evolutionary trend towards a reduction in both the number of proliferation zones and the overall number of newborn cells has been revealed in more recent lineages of vertebrates, such as mammals. Adult neurogenesis, and in particular the characterization of adult neural stem cells in mammals has been the focus of intense research with the goal of developing new cell-based regenerative treatments for neurodegenerative diseases, spinal cord injury, and acute damage due to stroke. Conversely, most other vertebrate classes, which display widespread production of adult neurons, are not typically used as model systems in this context. A more profound understanding of the structural composition and the mechanisms that support proliferation zones in the mature brain have become critical for revealing how adult neural stem cells are maintained in these regions and how they regulate neurogenesis. In this review we argue that comprehensive analyses of adult neurogenesis in various vertebrate and invertebrate species will lead to a more complete understanding of the fundamental biology and evolution of adult neurogenesis and provide a better framework for testing hypotheses regarding the functional significance of this trait.

Introduction

Adult neurogenesis appears to be a somewhat extreme and uneconomical form of structural remodeling, compared to the relatively subtle modifications in synaptic morphology that is known to mediate functional plasticity of neural circuitry. Nonetheless, it is precisely this attribute of adult neurogenesis that is beginning to redefine contemporary notions of neural plasticity. Thus, it is no surprise that the field of adult neurogenesis has in the last few decades become one of the most research-intensive fields in the neurosciences. However, despite the impressive progress made on delineating the molecular and cellular properties underlying the process of adult neurogenesis in a few laboratory models, we know very little about the anatomical organization, species diversity, functional significance and evolutionary history of this trait. The importance of understanding the basic cell biology of adult neurogenesis is paramount, but without considering how the natural environment regulates neurogenesis and how this trait has evolved, our understanding remains incomplete. Our current knowledge of adult neurogenesis rests on studies of no more than a few dozen species worldwide, and only a small subset of these species has undergone detailed anatomical mapping for the presence of this trait (Fig. 1). Considering that the animal kingdom consists of approximately 1.5 million known species, this represents a very tiny sampling of the potential diversity of adult neurogenesis.

Adult neurogenesis is broadly defined as the birth and maturation of new neurons that add to, or replace neurons in, existing circuitry under normal physiological or pathological conditions. Research on traditional vertebrate models continues to have a strong presence in the literature, comprised of detailed studies of rodents (Altman and Das, 1965, Altman, 1969, Kaplan and Hinds, 1977, Bayer et al., 1982, Corotto et al., 1993, Seki and Arai, 1995, Kuhn et al., 1996, Rietze et al., 2000, Liu and Martin, 2003, Maslov et al., 2004, Bauer et al., 2005) and songbirds (Goldman and Nottebohm, 1983, Nottebohm, 1985, Alvarez-Buylla and Nottebohm, 1988, Alvarez-Buylla et al., 1990, Nottebohm and Alvarez-Buylla, 1993, Barnea and Nottebohm, 1994, Nottebohm, 2002a, Nottebohm, 2002b, Margotta and Caronti, 2005). More recently mammalian research has been extended to the brains of New and Old World primates (McDermott and Lantos, 1990, Gould et al., 1999a, Gould et al., 1999c, Kornack and Rakic, 1999, Kornack and Rakic, 2001, Bernier et al., 2002, Koketsu et al., 2003, Ngwenya et al., 2006) and postmortem humans (Eriksson et al., 1998, Kukekov et al., 1999, Bédard and Parent, 2004). In the last 15 years, adult neurogenesis in the reptilian brain of selected species of lizards and turtles has been investigated (García-Verdugo et al., 1989, Perez-Sanchez et al., 1989, Pérez-Cañellas and García-Verdugo, 1996, Pérez-Cañellas et al., 1997, Font et al., 2001, Marchioro et al., 2005). By contrast, despite early experiments on the localization of adult neurogenesis in frogs and salamanders dating back to 1968, there are very few contemporary publications on amphibian adult neurogenesis (Minelli and Quaglia, 1968, Graziadei and Metcalf, 1971, Richter and Kranz, 1981, Mackay-Sim and Patel, 1984, Bernocchi et al., 1990, Polenov and Chetverukhin, 1993, Dawley et al., 2000). In the last decade, teleostean fishes have emerged as a prominent model, renowned for their robust neurogenic capacity throughout the adult CNS (Zupanc and Zupanc, 1992, Zupanc and Horschke, 1995, Zupanc et al., 1996, Zupanc et al., 2005, Maeyama and Nakayasu, 2000, Zikopoulos et al., 2000, Byrd and Brunjes, 1998, Byrd and Brunjes, 2001, Ekström et al., 2001, Adolf et al., 2006, Grandel et al., 2006, Zupanc, 2006).

Invertebrates have received little attention with respect to adult neurogenesis in comparison to their vertebrate counterparts. Our understanding of this biological trait stems primarily from two major invertebrate groups: insects and crustaceans. Crickets have long been the leading insect model (Cayre et al., 1994, Cayre et al., 1996, Scotto-Lomassese et al., 2000, Scotto-Lomassese et al., 2002, Malaterre et al., 2002), although a small number of other insect species have been examined (Norlander and Edwards, 1970, Technau, 1984, Ito and Hotta, 1992, Fahrbach et al., 1995, Booker et al., 1996, Cayre et al., 1996, Dufour and Gadenne, 2006). Laboratory studies of adult neurogenesis in crustaceans have been, for the most part, limited to a variety of species of crab (Harzsch and Dawirs, 1996, Schmidt, 1997, Schmidt and Harzsch, 1999, Hansen and Schmidt, 2001, Hansen and Schmidt, 2004, Sullivan and Beltz, 2005) and lobster (Harzsch et al., 1999, Schmidt, 2001). In addition to select arthropod species, convincing evidence of continual neurogenesis in adult hydrozoans (Phylum: Cnidaria) has also been presented (Sakaguchi et al., 1996, Miljkovic-Licina et al., 2004), but overall there have been very few studies in this area. To date, we have been unable to identify a single study that has examined adult neurogenesis in some of the most primitive invertebrate groups, namely annelids, nematodes, and flatworms. Nor has there been any investigation of this trait in chelicerates or myriapods, the other major classes of arthropod. Furthermore, there has been a general lack of research in more phylogenetically recent invertebrates, including molluscs, echinoderms, and protochordates. Finally, within the vertebrate and invertebrate models studied thus far the main, focus has been on the brain as the putative site of adult neurogenesis. Few studies have investigated whether this same trait is present in the spinal cord, sensory systems, autonomic, and peripheral nervous systems of animals. One exception has been the discovery of continual retinal neurogenesis in adult fishes (Johns, 1977, Johns and Easter, 1977, Meyer, 1978, Marcus et al., 1999, Ekström et al., 2001) and amphibians (Straznicky and Gaze, 1971, Dunlop and Beazley, 1981, Reh and Constantine-Paton, 1983, Wetts and Fraser, 1988, Wetts et al., 1989). An earlier account has also shown de novo neuronal proliferation in the normal spinal cord of a gymnotiform teleost (Anderson and Waxman, 1985). Moreover, reviews on the common properties of neurogenesis in the adult brain of invertebrates and vertebrates (e.g. Cayre et al., 2002) are rare compared to reviews that focus solely on adult neurogenesis in vertebrates (Alverez-Buylla and Lois, 1995, Scharff, 2000, Doetsch and Scharff, 2001, Zupanc, 2001a, Alvarez-Buylla et al., 2002, García-Verdugo et al., 2002, Lie et al., 2004, Mackowiak et al., 2004, Emsley et al., 2005, Abrous et al., 2005). Thus, the extent of shared and/or divergent characteristics of adult neurogenesis among animals is largely unexplored.

Correlations between adult neurogenesis and learning (Nottebohm, 1985, Nottebohm, 2002a, Nottebohm, 2002b, Nottebohm and Alvarez-Buylla, 1993, Denisenko-Nehrbass et al., 2000, Snyder et al., 2001, Scotto-Lomassese et al., 2003, Chambers et al., 2004, Enwere et al., 2004, Barker et al., 2005, Magavi et al., 2005, Alonso et al., 2006), seasonality (Alverez-Buylla and Lois, 1995, Clayton, 1998, Dawley et al., 2000, Nottebohm, 2002a, Nottebohm, 2002b, Hansen and Schmidt, 2004, Hoshooley and Sherry, 2004), and environmental stimuli (Ramirez et al., 1997, Scotto-Lomassese et al., 2000, Peñafiel et al., 2001) have been observed. While this list is far from comprehensive, these findings begin to unveil the extent to which adult neurogenesis plays a central role in, and is shaped by, the daily lives of adult species. The purpose of this review is to examine the anatomical and functional diversity and evolutionary trends of adult neurogenesis within the animal kingdom by considering the principle biological properties of this trait. We set in motion this review by first considering the definition of an adult species, and the variation in lifespan and growth across animals. Thereafter, this review is divided into five major sections, each discussing the current state of knowledge of the biological question at hand and proposing avenues for future research. Herein, we use the terminology “neurogenic compartment” to refer to the birthplace or proliferation zone of neurons.