The main hypothesis of this project proposes that the region surrounding the central canal in the spinal cord of young turtles is an active neurogenic zone in which Stem/Progenitor (S/P) cells proliferate, giving rise to immature neurons and glial cells. Connected with this hypothesis is the idea that immature neurons differentiate, migrate and integrate into pre-existing spinal circuits. Injuries and degenerative diseases of the spinal cord are among the most devastating ailments affecting many people. Understanding the biology of S/P cells in species that have retained neurogenesis after birth is crucial in order to develop adequate cell- replacement treatments.
The specific aims of this project are: 1) Identification and characterization of S/P cells in the spinal cord of the turtle, 2) to determine the morphological, fine structural, molecular and functional changes taking place during differentiation of newborn neurons from S/P cells, 3) to study the migration of newborn neurons from the central canal to the parenchyma and their subsequent functional integration into spinal circuitry, and 4) to assess the effects of injury on the production and differentiation of S/P cells. This proposal takes advantage of a unique biological model and applies a multidisciplinary approach involving immunocytochemistry, fine structure analysis, time-lapse imaging and electrophysiology. Both in vivo and in vitro preparations will be used. The immature cells characterized at the electrophysiolgical level will be further analyzed with molecular-structural techniques. Putative migratory behavior of immature cells will be investigated in vitro by means of time-lapse imaging of tagged cells. Finally, the modulatory influence of injury on proliferation and differentiation of S/P cells in animals at variable time points after a complete transection of the spinal cord, will be characterized by immunocytochemical, morphological and electrophysiological techniques. The proposed research will provide important information about the generation, maturation and integration of new neurons in mature sensory-motor circuitry. This knowledge is essential to understand basic neurogenic mechanisms that may remain """"""""dormant"""""""" in the mammalian spinal cord but could hopefully be """"""""awakened"""""""" to alleviate spinal cord diseases.
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