| Abstract No.: | 306 |
| Country: | Canada |
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| Title: | NEUROBIOLOGICAL FUNCTIONS OF GLUTAMATE KAINATE SUBTYPE RECEPTORS |
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| Authors/Affiliations: | 1 Min Zhuo*;
1 Department of Physiology, Faculty of Medicine, University of Toronto Center for the Study of Pain, University of Toronto, 1 King's College Circle, Toronto, ON, Canada
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| Content: | Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Ionotropic glutamate receptors contain three subtypes: NMDA, AMPA and kainate (KA) receptors. The former two receptor subtypes have well studied, while the roles of KA receptors are less characterized in part due to the lack of selective antagonists. In this talk, I will summarize our investigations of KA receptors using genetic knockout mice lacking GluR5 and/or GluR6 subtype receptors. By using in vitro brain slice preparations, we demonstrate that KA GluR5 modulates the release of GABA from local inhibitory neurons in the spinal cord dorsal horn, amygdala and anterior cingulate cortex. KA GluR6 receptor contributes to a small portion of synaptic transmission, and play a role in amygdala long-term potentiation (LTP). In in vivo behavioral studies, we found that behavioral responses to capsaicin or inflammatory pain were significantly reduced in mice lacking GluR5 but not GluR6 subunits. In classic fear memory tests, mice lacking GluR6 but not GluR5 showed a significant reduction in fear memory when measured 3, 7, or 14 days after training. Additionally, genetic deletion of GluR5 or local injection of a GluR5 antagonist into the basolateral amygdala increases anxiety-like behavior. Our findings provide evidence that distinct KAR subtypes contribute to chemical/inflammatory pain, fear and anxiety. Selectively targeting different KAR subtypes may provide a useful strategy for treating persistent pain and fear/anxiety-related mental disorders.
(Supported by grants from CIHR84256, CIHR66975, the EJLB-CIHR Michael Smith Chair, and Canada Research Chair)
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