KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Memory: From Sensory Circuits To Protein Conformations

    Thumbnail
    View/Open
    McGinnis_ku_0099D_15161_DATA_1.pdf (4.537Mb)
    Issue Date
    2017-05-31
    Author
    McGinnis, John Patrick
    Publisher
    University of Kansas
    Format
    121 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Molecular & Integrative Physiology
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    The ability to form, store, and retrieve memories is an essential capacity of many animals. Only in the past half-century, however, have the key neuronal and molecular events that underlie memory been studied. This has revealed a series of molecular cascades that are triggered by neuronal activation, ultimately leading to the stabilization of otherwise transient synaptic modifications. These synaptic modifications either increase or decrease the efficiency of synaptic transmission, thereby leading to altered neuronal communication. The behavioral events that must precede these molecular and neuronal changes, however, begin with the sensory system, where important information from the external world is identified. Generally, in situations involving associative learning, the experience of a reward or punishment is assumed to be remembered because of the relevance it holds for the organism at the moment of learning. Any pattern that deviates from this general idea provides an indication of exactly which features the processes of memory deem valuable. The deviation we explore here—that a more immediately appealing reward is not always better remembered, that D-arabinose is preferred to L-arabinose, but L-arabinose generates more reliable memories—suggests that there are important aspects beyond the momentary appeal of a reward. Further, L-arabinose, because it is remembered despite having no nutritional value, has allowed identification of a subset of 26 sensory neurons in Drosophila that, when activated, are sufficient to form long-term associative memories. In response to this sensory activation, the biochemical cascades of memory will, in further downstream neurons, trigger the oligomerization of the Drosophila cytoplasmic polyadenylation element binding (CPEB) protein, Orb2. Its oligomerization has so far been described as involving a prion-like conversion from a monomeric form to an amyloidogenic oligomer. Since its initial characterization, however, many types of functional protein oligomerization have been described. The question of whether Orb2’s oligomerization is in fact prion-like can best be addressed by substituting its prion domain with a variety of oligomerization domains, from other amyloid domains to more transient ‘liquid droplet’-type domains, or even standard tetramerization domains. Whether formation of less structured and less stable aggregates can still support the regulatory switch of Orb2 required for memory maintenance is the key question. Finally, Orb2 may not be the only functional prion-like protein in Drosophila, though it is the best characterized. Murashka, a RING-domain E3 ubiquitin ligase, is also involved in memory, and possesses both a disordered domain and features that are characteristic of prion-like proteins. If murashka does in fact undergo a prion-like conversion that is relevant for its role in memory, Orb2 will no longer be a curious outlier but instead the first illustration of what may be a widespread biological phenomenon.
    URI
    http://hdl.handle.net/1808/25886
    Collections
    • Dissertations [4475]
    • KU Med Center Dissertations and Theses [464]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps