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Tonotopic gradients of pre- and postsynaptic proteins in spiral ganglion neurons as established through the release and modulatory effects of BDNF and NT-3

by
Jacqueline Flores-Otero
B.S., 2002
Inter American University
Bayamon, Puerto Rico

Thesis Advisor: Robin L. Davis, Ph.D.

Graduate Program in Neuroscience

Nelson Biology Labs
Room D-406

Friday, February 6, 2009
10:00 am


Abstract

Tonotopic gradients are a hallmark of the auditory system, which decomposes complex sound from the external environment and delivers them to higher brain centers as individual frequencies. To understand the frequency-specific specializations that exist within the cochlea I have examined the distribution of pre- and postsynaptic proteins in spiral ganglion neurons.

The majority of spiral ganglion neurons (95%) form highly refined synapses of one to one connections with the receptor hair cells as they systematically align along the cochlea contour. The peripheral end forms a postsynaptic connection to the hair cells while the central projection terminates presynaptically onto cells in the cochlear nucleus. The precise arrangement makes them a suitable model system for examining whether pre- and postsynaptic proteins, which are targeted to opposite ends, are distributed according to frequency. Through this work I show that concurrent with the electrophysiological properties and ion channel distribution of spiral ganglion neurons (Adamson et al., 2002b), the protein levels of presynaptic (synaptophsin and SNAP-25) and postsynaptic (GluR2 and GluR3) proteins are greatly enriched in different frequency regions in postnatal and adult stages. The low frequency region (apex) displayed pronounced density of presynaptic proteins while the high frequency region (base) displayed pronounced density of postsynaptic proteins. Moreover, BDNF and NT-3, which are found in the cochlea, modulated these proteins such that BDNF upregulated postsynaptic proteins and NT-3 upregulated presynaptic proteins.

Taken together, these findings not only shed further insight into the mechanisms by which there gradients are established, but they emphasize the powerful impact that BDNF and NT-3 have in orchestrating the orderly organization of the cochlea and its afferent neural elements. This is important in the auditory field where neurotrophins are used to enhance the survival of spiral ganglion neurons upon the loss of their targets. If BDNF and NT-3 are capable of setting up physiological and biological features that are inherent to spiral ganglion neurons, novel approaches should be taken and graded delivery of these neurotrophins should be considered since they have proven to dynamically regulate numerous factors that are an essential part of the tonotopic arrangement of the auditory system.


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