Student Theses and Dissertations
Date of Award
1988
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Fernando Nottebohm
Keywords
adult neurogenesis, radial glia, neuronal migration, ventricular zone, canary brain, 3H-thymidine labeling
Abstract
The adult bird brain continues to produce new neurons and integrate them into functional circuits. These cells are born in the ventricular zone (VZ) of the lateral ventricle, sometimes up to 5-6 mm away from the location were some of these neurons finally mature (Nottebohm, 1985). How do new neurons find their way through the adult parenchyma away from the ventricle and into their final location? An antibody prepared against adult canary brain, 40E-C, stained ventricular zone cells that send long, unbranched processes into the telencephalon. Based on this morphology and their partial reactivity to GFAP we identified these cells as radial glia. The same antibody also stained a subset of brain astroglia and reacted with non-brain material such as mesenchyme, Sertoli cells and the Z-line of muscle. A weaker reaction was obtained with erythrocytes and some endothelial cells. 40E-C also reacted with radial glia of developing rat brain but failed to show any such glia in adult rodent brain. Western blot analysis showed that this antibody recognizes vimentin. The position of radial glia was systematically mapped in adult male and female canary brain. Radial glia fibers were found to orient mainly in the mediolateral plane and were more abundant in some parts of the telencephalon (e.g. hyperstriatum, caudal neostriatum and lobus parolfactorius) than in others (e.g. anterior neostriatum, archistriatum and septum), which had few or no radial glia fibers. Radial glia in mammals normally convert into adult astrocytes, their persistence into adulthood in birds probably relates to neurogenesis. This hypothesis is based on the following findings. A small, elongated cell type not previously described in adult avian brain was frequently seen to be associated with the long processes of the radial glia, oriented in the same direction and often in close apposition. Mapping the positions of these cells showed them to be almost unique to the telencephalon and therefore absent in regions where neurogenesis does not occur. It is then shown that the new elongated cells are the precursors of new neurons. At short survivals after [3H]-thymidine (a tag for dividing cells) injections, many VZ cells are labeled only on the lateral walls of the lateral ventricles. After three days from the last [3H]-thymidine injection, the number of labeled VZ cells drops as the number of labeled elongated cells increases. By day 20 the number of labeled elongated cells reaches a maximum and decreases thereafter as labeled neurons start to appear. One day after the last [3H]-thymidine injection, labeled elongated cells were present only very close to the VZ. Two days later the labeled elongated cells have moved laterally and by six days some of these cells are as far as 2.5 mm from the ventricle. Between days 15 and 20 these cells reach the most distant areas of the telencephalon. During the first week of migration most labeled elongated cells are found in regions rich in radial glia. The velocity of migration during the first 6 days is at least 20um per hour. Between days 6 and 15 the velocity drops to 8um per hour and we believe that this happens as many of the labeled elongated cells detach from the radial glia. Thus radial glia are used as fast dispersal pathways at least during the first week of migration. Since the number and distribution of labeled glia does not change with survival time, we conclude that the labeled elongated cells are migrating cells that differentiate only into neurons: that is, they are young migrating neurons. The number of migrating cells exceeds by a factor of 3 the number of new neurons that form. Many labeled picnotic (dying) cells can be seen at the time when migrating cells start to decrease in number. This raises the possibility that new neurons attain their final position by the selective survival of migrating cells only at sites where new neurons are required. New preliminary experimental approaches to adult neurogenesis are presented. These include, intraventricular injections of fluorogold to define the cytoplasmic anatomy of migrating neurons, the use of the antimitotic ARA-C to block neurogenesis and the precise mappmg of discrete zones of cell proliferation in the ventricular walls of the adult canary brain. The unique properties of neuronal migration in an adult brain provides a new model and new clues for the understanding of neurogenesis.
License and Reuse Information
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Recommended Citation
Alvarez-Buylla, Arturo, "Radial Glia and the Migration of Young Neurons in the Adult Avian Brain" (1988). Student Theses and Dissertations. 584.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/584
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy