• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    A critical role for glutamate in the organizational effects of estradiol on the developing hypothalamus

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Schwarz, Jaclyn M.
    Advisor
    McCarthy, Margaret M., 1958-
    Date
    2008
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Male and female brains exhibit fundamental morphological differences thought to underlie the differences in physiology and behavior between the sexes. In rodents, these sex differences are determined during a critical period of development, when testosterone secreted from the developing testes is converted to estradiol in neurons via the aromatase enzyme. This early estradiol exposure permanently differentiates the male from the female rodent brain by establishing sex differences in synaptic patterning, neuronal morphology and sex-typic behaviors. The medial basal hypothalamus (MBH) is a sexually dimorphic brain region that is responsive to estradiol. In newborn rats, males have twice the number of dendritic spines on hypothalamic neurons as females. Treatment of females with estradiol can rapidly increase the number of dendritic spines to levels seen in males. We determined that the estradiol-induced increase in dendritic spines in this region requires the activation of both AMPA and NMDA glutamate receptors. How does estradiol positively effect glutamatergic transmission in developing hypothalamic neurons? We hypothesized that estradiol enhances release of glutamate from presynaptic terminals. To test this hypothesis, cultured hypothalamic neurons were imaged with the fluorescent dye, FM4-64, which loads and unloads from presynaptic terminals upon depolarization. We found that estradiol significantly enhances neurotransmitter release from glutamatergic hypothalamic neurons in a receptor dependent manner, without the synthesis of new proteins, but requiring activation of PI3 kinase. Downstream of the glutamate receptor we further determined that MAP kinase activation is a necessary component of dendritic spine formation during this critical period. Based on these findings, our current working model for sexual differentiation of the MBH suggests that estradiol evokes glutamate release from developing hypothalamic terminals, activating both AMPA and NMDA receptors on the post-synaptic cell to stimulate MAP kinase and increase dendritic spines. We next predicted that these effects induce permanent defeminization of not only the brain, but also behavior. Blocking NMDA glutamate receptors during the critical period of sexual differentiation completely blocked estradiol-induced defeminization of behavior while having no effect on estradiol-induced masculinization of behavior. Surprisingly, females treated with NMDA postnatally showed not only behavioral defeminization but also masculinization during separate behavioral tests. We conclude that estradiol, via trans-synaptic NMDA receptor activation, permanently defeminizes adult sex behavior via its neonatal effects on neuronal morphology in the developing hypothalamus. These results are the first instance of a trans-synaptic mechanism by which estradiol permanently changes both the morphology and the function of neurons underlying a motivated behavior.
    Description
    University of Maryland, Baltimore. Neuroscience. Ph.D. 2008
    Keyword
    Biology, Neuroscience
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/982
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.