Degree Type

Dissertation

Date of Award

2002

Degree Name

Doctor of Philosophy

Department

Biomedical Sciences

First Advisor

Mirjana Randic

Abstract

To understand the physiological role of the AMPA-type or kainate-type ionotropic glutamate receptors and their participation in sensory information processing, including pain, it will be necessary to develop a comprehensive description of their actions in the adult mouse spinal cord substantia gelatinosa (SG) region. Without selective antagonists of the AMPA and kainate receptors, however, pharmacology has provided little assistance in this endeavor. In this study, gene-targeted mice lacking GluR2 AMPA subunit and GluR5 or GluR6 kainate receptor subunits were used to identify the receptor subunits that comprise the AMPA and KA receptors responsible for modulation of primary afferent neurotransmission.;AMPA receptors are not thought to be involved in the induction of UP of excitatory synaptic transmission in the SG region, but they may be involved in the expression via several messenger pathways. However, one subunit of the AMPA receptors, GluR2, is known to control Ca2+ influx. To test whether GluR2 plays any role in the induction of LTP, the mice lacking the subunit were used in the present work. In GluR2 mutants, UP in the SG region of spinal slices was markedly enhanced. These results suggest an important role for GluR2 subunit of AMPA receptors in regulating synaptic plasticity and pain behavior.;In this study, gene-targeted mice lacking GluR5 or GluR6 kainate receptor subunits have also been used to identify the receptor subunits that comprise the kainate receptors responsible for presynaptic modulation of primary afferent neurotransmission. In the presence of synaptic inhibition, both GluR5 and GluR6 subunits contribute to the depressant action of kainate at the C-fiber and Adelta-fiber-activated polysynaptic pathways. In the absence of synaptic inhibition, the GluR6 subunit is critically involved in inhibiting transmission at both Adelta- and C-fiber monosynaptic pathways, whereas GluR5 plays a lesser role in inhibiting the C-fiber-activated pathway. Both GluR5 and GluR6 KA receptor subunits contribute to the KA receptor-mediated facilitation of excitatory synaptic transmission at synapses on the SG neurons. These results indicate that AMPA and kainate receptors play multiple and complex roles in regulation of excitatory synaptic transmission in the spinal cord SG region with potentially significant implications for pain control.

DOI

https://doi.org/10.31274/rtd-180813-13150

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu

Copyright Owner

Dong-ho Youn

Language

en

Proquest ID

AAI3073490

File Format

application/pdf

File Size

127 pages

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