Year of Award


Document Type


Degree Type

Doctor of Philosophy (PhD)

Degree Name


Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Chair

Michael P. Kavanaugh

Commitee Members

Richard j. Bridges, Charles M. Thompson, J. Joshua Lawrence, Emily F. Stone


EAATs, glutamate, NMDARs


University of Montana


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.



© Copyright 2012 Katie Marie Hoffman