Date

December 2009

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Kainate receptors (KARs) contribute to postsynaptic excitation in only a select subset of neurons. To define the parameters that specify the postsynaptic expression of KARs, I examined the contribution of KARs to EPSCs on hippocampal interneurons in area CAI. Activation of the somatodentritic KARs through bath agonist applications indicated that interneurons in stratum radiatum/lacunosum-moleculare (SRISLM) express KARs both with and without the GluR5 subunit. However, activation of synaptic KARs through stimulus-evoked transmission indicated that only GluR5-containing KARs are targeted to the synapse. Since I was able to pharmacologically silence the synaptic KARs, I was also able to isolate the AMPAR EPSC on these interneurons, and found that AMPARs also contribute to the slowly decaying tail current. Spontaneous EPSCs with a conventional AMPAR component did not have a resolvable contribution of KARs, suggesting that the KARs that contribute to the evoked EPSCs are at a distinct set of synapses. Similarly, since the AMPAR sEPSCs did not have a slow tail component, the AMPARs that contribute to this component of the eEPSC are either segregated to separate synapses or mediated by glutamate spillover. GluR5-containing KARs do not contribute substantially to the EPSC in stratum oriens interneurons, but are present somatodendritically. I conclude that KARs are localized to synapses by cell type-, synapse-, and subunit-selective mechanisms. While the slow component of the AMPAR EPSG was preferentially recruited during block of glutamate transporters, it appears that the EPSC tail may actually reflect properties of the AMPARs rather than slow diffusion of glutamate out of the synapse. Since the AMPAR tail current is not sensitive to high frequency stimulation, recording at high temperatures, reduced probability of release, or preferential block by the low affinity antagonist y-DGG, it seems that the slow decay kinetics are not indicative of activation of extrasynaptic receptors by glutamate spillover. Surprisingly, the TBOA-recruited tail may also not reflect glutamate spillover as it was also not preferentially blocked by y-DGG.

Identifier

doi:10.6083/M4GM859H

Division

Neuroscience Graduate Program

School

School of Medicine

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