Glutamate is the major excitatory neurotransmitter in the brain and is crucial for processes such as learning and memory. Due its importance as a signaling molecule, the extracellular glutamate concentration is tightly regulated, largely by the excitatory amino-acid transporters (EAATs). In these studies, we investigated the role of EAAT1-3 in synaptic transmission at the Schaffer-CA1 synapse in acute hippocampal brain slices. My results demonstrated that transport block by L-TBA resulted in glutamate spillover and activation of NMDARs. Further investigation showed that L-TBA-mediated activation of NMDARs was facilitated by the Mg2+ unblock of the receptor. Furthermore our data indicate that NMDAR signaling was controlled by the interplay between several factors, including synaptic frequency, glutamate transport, Mg2+ block, and NMDAR channel kinetics. We propose that the observed theta frequency threshold for enhanced NMDAR signaling observed in physiological conditions is a consequence of a phase shifted signal at rhythms limited by NMDAR channel kinetics. We also found that dense fiber recruitment created conditions of spillover and glutamate pooling and therefore resulted in an increase in AMPAR desensitization at the hippocampal Schaffer-CA1 synapse. Overall my studies focused on the effects of glutamate spillover onto both NMDA and AMPA receptors at the Schaffer-CA1 synapse in hippocampal slice.
| Identifer | oai:union.ndltd.org:MONTANA/oai:etd.lib.umt.edu:etd-05092013-165429 |
| Date | 23 May 2013 |
| Creators | Hoffman, Katie Marie |
| Contributors | Joshua Lawrence, Emily Stone, Michael P. Kavanaugh, Richard Bridges, Charles Thompson |
| Publisher | The University of Montana |
| Source Sets | University of Montana Missoula |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.umt.edu/theses/available/etd-05092013-165429/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Montana or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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