I have attached the essay question and a couple of journals so the writter can have some idea of what type of references look for
Brain Size and Limits to Adult Neurogenesis Brain Size and Limits to Adult Neurogenesis Mercedes F. Paredes,1‡ Shawn F. Sorrells,2,3‡ Jose M. Garcia-Verdugo,4 and Arturo Alvarez-Buylla5* 1Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA 2Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA 3University of California, San Francisco, CA 94143, USA 4Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, CIBERNED 46980 Valencia, Spain 5Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Uni- versity of California, San Francisco, CA 94143, USA ABSTRACT The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neuro- genesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these pro- genitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ven- tricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indi- cates that the wall of the lateral ventricle is highly regional- ized, with progenitor cells giving rise to different types of neurons depending on their location. In species with larger brains, young neurons born in these spatially specified domains become dramatically separated from potential final destinations. Here we hypothesize that the increase in size and topographical complexity (e.g., intervening white matter tracts) in larger brains may severely limit the long- term contribution of new neurons born close to, or in, the ventricular wall. We compare the process of adult neuronal birth, migration, and integration across species with differ- ent brain sizes, and discuss how early regional specification of progenitor cells may interact with brain size and affect where and when new neurons are added. J. Comp. Neurol. 524:646–664, 2016. VC 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. INDEXING TERMS: neuronal replacement; regional specification; brain evolution; comparative neuroanatomy; plasticity In his book Degeneration and Regeneration of the Nervous System, Ram�on y Cajal (1928) wrote that: “In adult centres the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated.” Following Ram�on y Cajal’s identification of nerve cells as independent units of brain circuits, it became deeply established in the neurosciences, as well as by the general public, that no new neurons are added to the brain once fetal development is complete. This dogma persisted for most of the 20th century until [3H]thymidine became available for cellular birthdating. The incorporation of [3H]thymidine into dividing cells was used in conjunction with Nissl staining to identify newly born cells with neuronal morphology. Work using this approach suggested that new neurons are born in multiple brain regions in adulthood. The regions where labeled cells were found included the cortex of the rat, the granule cell layer of the hippocampal dentate gyrus in the rat and the cat (Altman, 1963), and the rat olfactory bulb (OB) (Altman and Das, 1967; Bayer and Altman, 1975). Subsequent ultrastructural studies This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and dis- tribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Arturo Alvarez-Buylla is the Heather and Melanie Muss Endowed Chair of Neurological Surgery at UCSF. ‡The first two authors contributed equally to this work. Grant sponsor: U.S. National Institutes of Health; Grant numbers: NS28478 and HD032116; Grant sponsor: California Regenerative Medi- cine Clinical Fellowship (to M.P.); Grant sponsor: National Research Service Award, National Institutes of Health Fellowship; Grant number: F32MH103003 (to S.S.). *CORRESPONDENCE TO: Arturo Ivarez-Buylla, University of California, San Francisco, Department of Neurological Surgery, 35 Medical Center Way RMB-1038, Box 0525, San Francisco, CA 94143-0525. E-mail: ABuylla@stemcell.ucsf.edu Received February 27, 2015; Revised August 28, 2015; Accepted September 8, 2015. DOI 10.1002/cne.23896 Published online September 28, 2015 in Wiley Online Library (wileyonlinelibrary.com) VC 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. 646 The Journal of Comparative Neurology |Research in Systems Neuroscience 524:646–664 (2016) REVIEW http://creativecommons.org/licenses/by-nc-nd/4.0/ http://creativecommons.org/licenses/by-nc-nd/4.0/ supported the idea that the adult rat dentate gyrus and OB contain young neurons (Kaplan and Hinds, 1977). The interpretation of these results was questioned for several reasons: 1) the possibility that [3H]thymidine labeling was not in new neurons but in closely adjoining proliferative glial cells; 2) the radioactive labeling (rela- tively few grains per cell) might have been insufficient to reflect true cell division; and 3) the putative labeled cells could have incorporated [3H]thymidine due to DNA repair (Rakic, 1985, 2002a). Although controversial, this initial work was the first evidence of adult incorporation of new neurons in the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus and the OB, sites that have been confirmed in subsequent studies (reviewed in Fuentealba et al., 2012; Yu et al., 2014). Renewed interest in adult neurogenesis came from independent studies in songbirds, a model organism to study vocal learning (Thorpe, 1954; Nottebohm, 2004). Seasonal changes in the size of a key region of the song control pathway, the high vocal center (HVC), were found to correlate with changing levels of testosterone (Nottebohm, 1981). Short survivals after [3H]thymidine exposure revealed the presence of dividing cells within the ventricular zone (VZ) on the walls of the lateral ven- tricles (Fig. 1). With longer [3H]thymidine postlabeling intervals, labeled neurons were found in the HVC (Goldman and Nottebohm, 1983). Further work using electrophysiology confirmed the neuronal identity of the labeled cells (Paton and Nottebohm, 1984). New neu- rons were found to synaptically integrate within the HVC (Paton and Nottebohm, 1984; Burd and Nottebohm, 1985) and send projections to the distant nucleus robus- tus archistriatalis (RA) (Alvarez-Buylla and Kirn, 1997). The amount of adult neurogenesis in birds correlates with seasonal and hormonal patterns, and with complex experiences, suggesting a possible functional role in plasticity and/or learning (Barnea and Nottebohm, 1994; Nottebohm et al., 1994; Alvarez-Buylla and Kirn, 1997; Nottebohm, 2004). This work clearly demonstrated that the newly added neurons can become part of functional circuits in the adult brain, and are involved in an ongoing process of neuronal replacement (Nottebohm, 2004). Early investigators assumed that the progenitor cells for adult neurogenesis would be simple and undifferentiated, possibly cells retained from fetal development (Altman, 1969), but work in songbirds demonstrated that this is not the case. Radial glia (RG) cells in the adult songbird VZ (Fig. 2) were found to incorporate [3H]thymidine, and their division correlated with the production of young neu- rons, providing the first evidence that these cells are the adult neural stem cells (NSCs) (Alvarez-Buylla et al., 1990a). These and other studies using birds provided sev- eral levels of evidence for adult neurogenesis including the identification of proliferating neuronal progenitors, electrophysiological and ultrastructural identification of the new neurons, and a possible functional importance for their integration into established adult circuits. THE CHALLENGE OF ADDING NEW NEURONS The addition of new neurons into an adult network requires the coordination of cell division, migration, maturation, and integration into existing circuits. To begin, progenitor cells must be maintained for extended periods of time past embryogenesis into adulthood to generate new neurons. This continued proliferation in the adult brain must be regulated, as the presence of dividing NSCs into adulthood has been proposed as a possible source for brain tumors (Jacques et al., 2010; Alcantara Llaguno et al., 2011; Cuddapah et al., 2014). Next, young neuroblasts need to migrate varying distan- ces based on their birthplace using cues to guide them to their final destination (Rousselot et al., 1995; Lim et al., 1997; Wu et al., 1999; Hack et al., 2002; Bolteus and Bordey, 2004). The distances that separate sites of origin from destinations in the juvenile and adult brain result in migratory routes that 1) are orders of magnitude longer than in the embryo, when the brain is relatively small, (Figs. 3 and 4) contain more complexities, such as extensive vascularization, increasing regions of white matter, and a very dense network of mature dendrites, axons, and synapses. Once the young neurons complete this journey, they must begin the process of integration into fully functional networks, without deleterious effects on the working of these circuits (Nottebohm, 2004; Song et al., 2005; Lazarini and Lledo, 2011). We suggest that amidst these challenges, one of the most important restrictions to widespread adult neurogenesis is brain size. Given the early regional specification of NSCs in development, the increased migration requirements on young neurons and the changes in the architecture of neurogenic zones in a larger brain may impose strict limi- tations for the delivery of neurons to many brain regions. These structural constraints may also lead to variability in adult neurogenesis between species. ADULT NEUROGENESIS IN SPECIES WITH DIFFERENT BRAIN SIZES Adult neurogenesis in the ventricular subventricular zone (V-SVZ) has been described in greatest detail in species with small brains like rodents, birds, and rep- tiles, making it difficult to evaluate the influence of brain size on this process. Species with larger brains (especially humans) are more technically challenging to study, which greatly limits our ability to accurately Brain Size and Limits to Adult Neurogenesis The Journal of Comparative Neurology |Research in Systems Neuroscience 647 Figure 1. Neurogenic zones and migration destinations across several species and their relationship to brain size. Left column: Dorsal view of the brains of several species all scaled according to the 1-cm scale bar at the bottom left. Middle column: Sagittal view of each brain at the parasagittal plane of the RMS and olfactory bulb in each species. Green regions indicate germinal zones. Red dots indicate destinations of the migratory young neurons. Bottom row is scaled according to the lower left 1-cm scale bar; other sections are not to scale. Right column: Coronal view of each brain. (Reptile): The lizard P. hispanica is shown as an example of adult neurogenesis in the reptile. (Bird): The canary is shown, highlighting the extensive ventricular germinal zone and regions that continue to receive adult born neurons. (Rodent): The adult mouse has a pronounced rostral migratory stream from the ventricles as well as abundant hippocampal neu- rogenesis. (Monkey): The macaque is one of the original non-human primates in which adult neurogenesis was studied. Progenitor cells are abundant along the SVZ, cells proliferate and migrate along the RMS to the OB,