Year of Award
Doctor of Philosophy (PhD)
Department or School/College
Department of Biomedical and Pharmaceutical Sciences
Michael P. Kavanaugh
Richard J. Bridges, J. Joshua Lawrence, Nicholas R. Natale, Sarah J. Certel, Leonid V. Kalachev
University of Montana
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. An accurate spatial and temporal glutamate concentration profile during signaling is crucial for reliable neural computation. In these studies, we investigated the roles of glutamate transporters in controlling both ambient glutamate levels and dynamic glutamate concentrations profiles during synaptic transmission. Using the Xenopus oocyte expression system, we demonstrated that glutamate transporters act as an effective sink and are capable of maintaining >200 fold glutamate concentration gradient between the bath and cell surface when expressed at levels corresponding to physiological transporter densities in the CNS. We also characterized the specificity and actions of a new arylasparate glutamate transport inhibitor at the Shaffer collateral-CA1 pyramidal cell synapse in hippocampus, and demonstrated that glial glutamate transporters tightly control synaptically released glutamate and further, through cooperation with voltage-dependent Mg2+ block, they influence the magnitude and frequency-dependence of postsynaptic NMDA receptor signaling.
Sun, Weinan, "Glutamate transporter modulation of ambient and synaptic glutamate levels" (2014). Graduate Student Theses, Dissertations, & Professional Papers. 10759.
© Copyright 2014 Weinan Sun