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Scientific Projects (2008-2009)



Dr. Kenira Thompson
Title: Glutamate Transporters and Hippocampal Plasticity


The overall goal of this proposal is to address the role of glutamate transporters on memory mechanisms. While most studies of memory mechanisms focus on either hippocampal presynaptic transmitter release or postsynaptic receptors, few have characterized the role of glutamate transporters in modulating synaptic efficacy in this structure. Interestingly, one study found increases in glutamate transporter mRNA at the Schaffer collateral-CA1 hippocampal pathway following long-term potentiation (LTP) and fear conditioning (Levenson et al., 2002). While this increase in glutamate transporter expression immediately following LTP is understandable (to clear excess glutamate following LTP), the increase following contextual fear conditioning is not as clear. It seems more probable that contextual fear learning would elicit a down-regulation of glutamate transporter, in order to augment synaptic efficacy in the hippocampus. In fact, work performed while I was a postdoc at the Univ. of Texas at San Antonio, found an increase of the glutamate transporter GluT mRNA 1 hr after LTP at the opioid-dependent mossy fiber-CA3 pathway, and a decrease of the same transporter following spatial learning of a water maze. Due to its location and connectivity, the mossy fiber projection to CA3 is considered a major player in the processing of contextual memories, yet little is known regarding the role of glutamate clearance at this synapse. Our previous work suggests that glutamate transporters exert a regulatory role in mossy fiber plasticity. In this proposal, we will further assess the role of specific neuronal and glial glutamate transporters on mossy fiber plasticity following in vivo LTP and hippocampal learning by isolating the pre and post-synaptic components of the mossy fiber synapse using laser capture microdissection (LCM). In Specific Aim 1, we will determine if glutamate transporters increase on glia and neurons at the mossy fiber synapse of the hippocampus following mossy fiber-CA3 long term potentiation in vivo. In Specific Aim 2, we will determine if neuronal and/or glial glutamate transporters are down-regulated at the mossy fiber synapse following spatial learning on a Morris water maze. The central hypothesis is that glutamate transporters exert a modulatory role at the mossy fiber synapse during LTP and learning. Understanding the modulation in hippocampal plasticity could lead to interventions to augment hippocampal functioning in memory-related disorders.
 


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