Elements of the general plastic response of the brain, ranging from synaptic proliferation and structural modification to modifications of non-neural elements have been under study by a large number of neuroscience laboratories. A variety of changes in the structure Of individual synapses, as well as changes in the number and pattern of synapses, have been described in Paradigms ranging from electrically-induced long-term Potentiation in vitro to various types of adult learning. As a result, these changes have tended to be viewed individually as potential forms of efficacy or circuitry change, rather than as components of an overall pattern or set of patterns that define a coherent plastic process. This proposal seeks to understand neural plasticity in a more complete context. Both plasticity of synapse number--the formation and loss of synapses-and plasticity of synapse structure--the presumed modification of previously existing synapses--will be investigated in the occipital cortex of young and adult rats housed in complex or individual cage environments. The experimental plan combines use of Phaseolus vulgaris leucoagglutinin (PHA-L), wheat germ agglutinin-horseradish peroxidase (WGA-HRP), and l,l',dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Di-I) based analysis of afferent axons with current source density (CSD) analysis of responses evoked by activation of these afferents. Subjects will be rats in which these afferents have (or have not) been altered as a consequence of housing in a complex environment. Electron microscopic analysis of PHA-L labelled synapses will evaluate modifications in the structure of synapses in identified afferent systems to determine which forms of structural plasticity are dissociated from plasticity of synapse number, and hence are the most likely candidate substrates for synaptic efficacy change. Functional correlates of structural modifications will be assessed through laminar CSD analysis of responses evoked by activation of the particular afferent system under study. Parallel experiments will examine two additional key components of the general plastic process as exhibited in the EC-IC rat model: changes in the number and structure of astrocytes and changes in the structure of the capillary network. Thus the proposal seeks to develop an integrated understanding of the process of neural plasticity, as exhibited in the rat occipital cortex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH035321-08
Application #
3486514
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1983-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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
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
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
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
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
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
Grossman, Aaron W; Elisseou, Nicholas M; McKinney, Brandon C et al. (2006) Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature-appearing profile of dendritic spines. Brain Res 1084:158-64
Grossman, Aaron W; Aldridge, Georgina M; Weiler, Ivan Jeanne et al. (2006) Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond. J Neurosci 26:7151-5
Markham, Julie A; Beckel-Mitchener, Andrea C; Estrada, Christina M et al. (2006) Corticosterone response to acute stress in a mouse model of Fragile X syndrome. Psychoneuroendocrinology 31:781-5

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