Date

December 2009

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Glutamate is the primary neurotransmitter governing excitatory synaptic transmission in the central nervous system. Because glutamate is not enzymatically degraded, after release from vesicles into the synaptic cleft or from other sources, it must be removed from the extracellular space. This task is accomplished by Na+-dependent high-affinity glutamate transporters. Glutamate uptake by transporters prevents excitotoxicity and maintains the precision of synaptic transmission. In this thesis, I explored the role of transporters in controlling glutamate concentrations in and around synapses. In Chapter 1, we designed experiments to estimate the ambient concentration of glutamate in the extracellular space of rodent hippocampal brain slice. The value was ~25 nM, which is lower than the sensitivity of most glutamate receptors. Transporter function was necessary to maintain this low concentration of extracellular glutamate. We examined this finding in more detail in Chapter 2, exploring the distribution of ambient glutamate in the hippocampal neuropil. Extracellular glutamate is low throughout the neuropil indicating that transporters are not positioned to preferentially protect synaptic structures from ambient glutamate exposure. Instead, transporters prevent tonic activation of both synaptic and extrasynaptic receptors by maintaining low concentrations of ambient glutamate, likely due to the high density of transporters throughout the synapse-rich neuropil. These roles are integral in maintaining precise synaptic transmission.

Identifier

doi:10.6083/M4GH9FX7

Division

Neuroscience Graduate Program

School

School of Medicine

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.