• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Kctd12 and Ulk2 partner to regulate habenular dendritogenesis and behavior / spinophilin regulates dendritic spine formation and F-actin dynamics in hippocampal neurons

    Lee, Stacey Nicole
    : https://etd.library.vanderbilt.edu/etd-05202016-115604
    http://hdl.handle.net/1803/12348
    : 2016-08-04

    Abstract

    Appropriate neuronal morphogenesis is essential for forming the distinct functional domains of each of the hundreds of types of neurons in the brain. Generating the correct size and shape of dendrites is essential for a neuron to satisfactorily sample and process the signals that converge on its dendritic field. Understanding the control of neuronal circuit development is key to understanding normal and abnormal brain function and behavior. The habenular nuclei of the limbic system regulate responses, such as anxiety, to aversive stimuli in the environment. The habenulae receive inputs from the telencephalon via elaborate dendrites that form in the center of the nuclei. The kinase Ulk2 positively regulates dendritogenesis on habenular neurons, and in turn is negatively regulated by the cytoplasmic protein Kctd12. Given that the habenulae are a nexus in the aversive response circuit, we suspected that incomplete habenular dendritogenesis would have profound implications for behavior. We find that Ulk2, which interacts with Kctd12 proteins via a small proline-serine rich domain, promotes branching and elaboration of dendrites. Loss of Kctd12 results in increased branching/elaboration and decreased anxiety. We conclude that fine-tuning of habenular dendritogenesis during development is essential for appropriate behavioral responses to negative stimuli. In addition to dendritic shaft development, dendritic spine development is a key event in synapse formation. Dendritic spines are protrusions emanating from the dendritic shaft that interact with axons to form excitatory synapses. Here we show that spinophilin/neurabin II, a scaffolding protein that is highly expressed in dendritic spines, has an important role in dendritic spine and synapse formation in hippocampal neurons. Knockdown of endogenous spinophilin with a short hairpin RNA (shRNA) causes a significant decrease in synapse and spine density, as shown by immunostaining for the presynaptic marker synaptic vesicle protein 2 and the postsynaptic marker postsynaptic density protein 95. On the other hand, expression of mCherry-spinophilin results in an increase in spine density. These results suggest that spinophilin is critical for dendritic spine and synapse formation. We hypothesized that spinophilin was promoting dendritic spine and synapse formation by regulating F-actin accumulation. Indeed, expression of GFP-spinophilin led to an increase in the amount of F-actin in spine heads. Collectively our data demonstrate an important function for spinophilin in modulating the formation of dendritic spines and synapses.
    Show full item record

    Files in this item

    Icon
    Name:
    LeeDissertationFinalUpload.pdf
    Size:
    6.934Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy