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Afferent Regulation of Neuronal Survival in the Avian Cochlear Nucleus

Title: Afferent Regulation of Neuronal Survival in the Avian Cochlear Nucleus.
Name(s): Nicholas, Alexander H., author
Hyson, Richard L., professor directing dissertation
Logan, Timothy, outside committee member
Joiner, Thomas, committee member
Fadool, Debra Ann, committee member
Johnson, Frank, committee member
Department of Psychology, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2005
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Development of the central nervous system is guided by patterns of molecular expression and by cellular interactions. One important component of the cellular interactions that guide development of neural pathways relates to the electrical activity of neurons and the chemical signals released from active nerve fibers. A role of neural activity in guiding development is especially important in the development of sensory pathways. The elimination of afferent activity results in cell death and atrophy in a variety of sensory systems and many of these effects are most pronounced in developing systems. The purpose of this report is to further the understanding of the activity-dependent signals that are necessary for maintaining healthy neurons and to examine the sequence of events that lead towards death following the loss of afferent activity. The chick auditory brain stem has been a useful model system for examining the afferent-dependent signals that regulate postsynaptic neurons. Like other sensory systems, compromised afferent input results in rapid death and atrophy of postsynaptic neurons. To understand the afferent regulation of cell viability, one must examine: 1) the intercellular signals that serve as trophic factors, and 2) the intracellular chain of events that lead towards cell death. The studies in this dissertation explore aspects of both issues. First, anatomical techniques are used to evaluate the expression of a receptor called metabotropic glutamate receptor (mGluR) that is believed to play a role in maintaining the health of auditory neurons. Second, the possible contributions of an oxidative stress pathway in determining neuronal fate following deafferentation were also explored. Towards this end, levels of reactive oxygen species (ROS), lipid damage measured by 4-hydroxynonenal (4-HNE) formation, and a compensatory ROS response regulated by glutathione s transferase M1 (GSTM1) and the ROS-sensitive transcriptional factor, nuclear respiratory factor 1 (Nfr1) were examined. Unilateral cochlea removal surgery was performed on chicks ages P0-P1 and P7-P10. Opposite sides of the same tissue sections were compared for analysis. These studies confirmed that mGluRs are located in the auditory system and their expression appears to increase early following cochlea removal. Evidence was also provided to support a role for oxidative stress in determining neuronal survival following deafferentation. A dramatic increase in ROS was accompanied by lipid damage and a compensatory upregulation of both GSTM1 and Nrf1 following cochlea removal. Together, these data identify some anatomical features of mGluR localization and suggest an oxidative pathway that might be significant in determining whether a given neuron survives following deafferentation.
Identifier: FSU_migr_etd-2610 (IID)
Submitted Note: A Dissertation submitted to the Program in Neuroscience in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Degree Awarded: Summer Semester, 2005.
Date of Defense: June 30, 2005.
Keywords: Mitochondria, Reactive Oxygen Species, Avian, Auditory System, Cell Death, Deafferentation
Bibliography Note: Includes bibliographical references.
Advisory Committee: Richard L. Hyson, Professor Directing Dissertation; Timothy Logan, Outside Committee Member; Thomas Joiner, Committee Member; Debra Ann Fadool, Committee Member; Frank Johnson, Committee Member.
Subject(s): Neurosciences
Persistent Link to This Record:
Host Institution: FSU

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Nicholas, A. H. (2005). Afferent Regulation of Neuronal Survival in the Avian Cochlear Nucleus. Retrieved from