It is generally accepted that atypical afferent input to sensory systems during development can lead to a number of abnormalities in target neurons and can even end in cell death. The brainstem auditory system of the chick proves to be a useful model for examining deafferentation-induced changes. Within the auditory brainstem of the chick, the VIIIth cranial nerve bifurcates, transmitting information from the cochlea to two nuclei, Nucleus Angularis (NA) and Nucleus Magnocellularis (NM), providing these neuronal populations with their sole excitatory input. The elimination of afferent drive through cochlear ablation results in the death of approximately 30% of neurons in NM and some assays can segregate cells into living and dying populations by ~6 hrs following deafferentation. A disruption in cellular metabolism, including the rise in intracellular calcium and reduction in protein synthesis, can be visualized as early as 1 hr following cochlea removal. The early changes that occur following deafening can be investigated through the use of an in vitro slice preparation and suggest that loss of mGluR activation is responsible for the rapid changes that occur as a result of afferent deprivation. Two major limitations exist with the current data: first, mGluR effects have only been established through in vitro studies for early changes that are observed in all deafferented neurons, from which most of the cells (70%) recover. Consequently, it is not known if mGluR activation is truly necessary to prevent the ultimate death of the subpopulation of NM neurons in an intact animal. Second, it is not known if mGluR activation is sufficient to maintain the metabolic machinery of NM neurons in a healthy state or if other activity-dependent factors are also necessary. Novel in vivo and in vitro methods were utilized to assess both mGluR receptor blockade and activation, respectively. The role of mGluRs in the intact system was investigated by pharmacologically blocking mGluR receptors in NM over various times following cochlea removal. The second set of experiments in this work investigated the sufficiency of mGluR activation in maintaining postsynaptic metabolic machinery of NM through the focal, periodic application of agonists via pressure ejection to neurons on one side of an in vitro slice preparation leaving the opposite side of the same slice unaffected. Both experiments demonstrated that NM neurons rely on mGluR activation for survival and normal neuronal maintenance. / A Dissertation submitted to the Department of Psychology in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / March 29, 2012. / Auditory System, Cell Death, Deafferentation, mGluRs, Nucleus Magnocellularis, Y10B / Includes bibliographical references. / Richard L. Hyson, Professor Directing Dissertation; Joanne Lasker, University Representative; Barbara Licht, Committee Member; Frank Johnson, Committee Member; Michael Meredith, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_182800 |
| Contributors | Carzoli, Kathryn L. (Kathryn Lynn) (authoraut), Hyson, Richard L. (professor directing dissertation), Lasker, Joanne (university representative), Licht, Barbara (committee member), Johnson, Frank (committee member), Meredith, Michael (committee member), Department of Psychology (degree granting department), Florida State University (degree granting institution) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource, computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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