Examination of Molecular Mechanisms Underlying Developmental and Adult Learning-Associated Plasticity in the Rat Brain

155 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1993.The work presented in this thesis examined the expression of two proteins, a transcription factor, Fos, which influences cellular change at the genomic level, and a cytoskeletal protein, Flatmap 1, involved in dynamic change of the cell at such localized areas as the cell soma or processes. These proteins were of interest because of their potential roles as underlying mechanisms and possible markers of developmental and adult-learning associated plasticity. Experiment 1 examined expression of the immediate early gene protein product Fos and related proteins (Fos-related proteins) in the rat brain during development when cell differentiation is prevalent using immunocytochemistry with a Fos-specific and a Fos and Fos related protein-specific antibody. Results of the study showed that Fos and Fos-related antigens are differentially expressed in the developing brain prior to and during peak times of cell differentiation in a region- and cell-specific manner. Fos may, therefore, be a useful marker of plasticity and part of the molecular mechanisms that give rise to plastic change in the developing brain. Experiment 2 examined Fos expression in the adult cerebellum following forelimb reach training using the Fos-specific antibody. The cerebellum has been implicated in motor learning aspects of this task and has previously shown learning-associated plastic change. Fos, however, was not significantly enhanced in cerebellar forelimb areas following training, although there was a nearly significant tendency in this direction. Future studies, with such changes as increased sample size, examination of different brain areas, assessment of learning by the percent of accurate reaches, and the use of more robust learning paradigms may detect learning-induced levels of Fos. Experiment 3 examined Flatmap 1 expression following forelimb reach training. Protein expression was quantified using densitometric analysis of immunolabelled tissue sections in forelimb areas of cerebellum and cerebral cortex and in the CA1 subfield of the hippocampal formation. Flatmap 1 did not show a learning induced response. The results presented in this thesis strongly implicate Fos and related antigen expression in neuronal differentiation and suggest possible involvement in adult motor learning.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD