While neuroscience has made rapid advances with regard to the molecular biology of the brain, the lack of knowledge at more molar levels has sometimes been disarmingly surprising, as in the belated recognition of post-developmental neurogenesis in at least some regions of the adult brain. Our knowledge of the plasticity of nonneural cells in the CNS is even more limited than our knowledge of neuronal plasticity, aside from studies of single gene mutations and pathology. It is clear from our work that astrocytes, oligodendrocytes and vascular tissue exhibit morphological plasticity in response to experience that often quantitatively equals or exceeds the plasticity seen in neuronal measures such as dendritic field dimensions and synapse numbers. We have found, for example, dramatic increases in myelination of the corpus callosum in adult rats exposed to a complex environment. There is abundant evidence that these supporting cells can affect information processing by neurons in significant ways such as modulating synaptic efficacy in response to propagated calcium waves in astrocytes, selectively increasing axonal conduction and altering gene expression patterns in the neurons they envelop. Moreover, while there is controversy regarding post-developmental neurogenesis in regions outside of the dentate gyrus and basal forebrain-olfactory bulb, there is wide agreement that glial and vascular tissue continue to proliferate into adulthood in at least most brain regions in which this has been investigated. Indeed a principal difficulty in demonstrating neurogenesis has been differentiating it from proliferation of glial and vascular tissues. Yet we know very little about proliferation and plasticity of these support tissues and how they might contribute to brain function. This research proposes to examine the effects of experience upon neurogenesis and non-neuronal cells of the cerebral cortex, to sort out regulatory effects upon proliferation and hypertrophy and the neural mechanisms mediating these regulatory effects. The experiential manipulation to be used, exposure to a complex physical and social environment, has dramatic effects on cerebral cortical organization, nearly doubling, for example, vascular volume per neuron, compared to that of rats reared in individual laboratory cages. Studies are proposed to investigate the effects of experience upon the proliferation and modification of oligodendrocytes, astrocytes, microglia and vasculature in the context of experience effects upon the plasticity of neurons and their synapses, using DNA-labeling, protein-impregnating and optical and electron microscopic methods.

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National Institute of Mental Health (NIMH)
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Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
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Sieber, Beth-Anne
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Annangudi, Suresh P; Luszpak, Agatha E; Kim, Soong Ho et al. (2010) Neuropeptide Release is Impaired in a Mouse Model of Fragile X Mental Retardation Syndrome. ACS Chem Neurosci 1:306-314
Kao, Der-I; Aldridge, Georgina M; Weiler, Ivan Jeanne et al. (2010) Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci U S A 107:15601-6
Grossman, Aaron W; Aldridge, Georgina M; Lee, Kea Joo et al. (2010) Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1 knockout mice. Brain Res 1355:221-7
Moy, S S; Nadler, J J; Young, N B et al. (2009) Social approach in genetically engineered mouse lines relevant to autism. Genes Brain Behav 8:129-42
Markham, Julie A; Herting, Megan M; Luszpak, Agatha E et al. (2009) Myelination of the corpus callosum in male and female rats following complex environment housing during adulthood. Brain Res 1288:9-17
Berry-Kravis, Elizabeth; Sumis, Allison; Hervey, Crystal et al. (2008) Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 29:293-302
Aldridge, Georgina M; Podrebarac, David M; Greenough, William T et al. (2008) The use of total protein stains as loading controls: an alternative to high-abundance single-protein controls in semi-quantitative immunoblotting. J Neurosci Methods 172:250-4
Kim, Soong Ho; Markham, Julie A; Weiler, Ivan Jeanne et al. (2008) Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proc Natl Acad Sci U S A 105:4429-34
Kleim, Jeffrey A; Markham, Julie A; Vij, Kapil et al. (2007) Motor learning induces astrocytic hypertrophy in the cerebellar cortex. Behav Brain Res 178:244-9
Kim, Soong Ho; Dong, Willie K; Weiler, Ivan Jeanne et al. (2006) Fragile X mental retardation protein shifts between polyribosomes and stress granules after neuronal injury by arsenite stress or in vivo hippocampal electrode insertion. J Neurosci 26:2413-8

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