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The Journal of Neuroscience, October 11, 2006, 26(41):10461-10471; doi:10.1523/JNEUROSCI.2579-06.2006
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Cellular/Molecular
Different Mechanisms Exist for the Plasticity of Glutamate Reuptake during Early Long-Term Potentiation (LTP) and Late LTP
Juan D. Pita-Almenar, Maria Sol Collado, Costa M. Colbert, andArnold Eskin Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5001
Correspondence should be addressed to Arnold Eskin, Department of Biology and Biochemistry, University of Houston, 369 Science & Research II, Houston, TX 77204-5001. Email: eskin{at}uh.edu
Regulation of glutamate reuptake occurs along with several forms of synaptic plasticity. These associations led to the hypothesis that regulation of glutamate uptake is a general component of plasticity at glutamatergic synapses. We tested this hypothesis by determining whether glutamate uptake is regulated during both the early phases (E-LTP) and late phases (L-LTP) of long-term potentiation (LTP). We found that glutamate uptake was rapidly increased within minutes after induction of LTP and that the increase in glutamate uptake persisted for at least 3 h in CA1 of the hippocampus. NMDA receptor activation and Na+-dependent high-affinity glutamate transporters were responsible for the regulation of glutamate uptake during all phases of LTP. However, different mechanisms appear to be responsible for the increase in glutamate uptake during E-LTP and L-LTP. The increase in glutamate uptake observed during E-LTP did not require new protein synthesis, was mediated by PKC but not cAMP, and as previously shown was attributable to EAAC1 (excitatory amino acid carrier-1), a neuronal glutamate transporter. On the other hand, the increase in glutamate uptake during L-LTP required new protein synthesis and was mediated by the cAMP–PKA (protein kinase A) pathway, and it involved a different glutamate transporter, GLT1a (glutamate transporter subtype 1a). The switch in mechanisms regulating glutamate uptake between E-LTP and L-LTP paralleled the differences in the mechanisms responsible for the induction of E-LTP and L-LTP. Moreover, the differences in signaling pathways and transporters involved in regulating glutamate uptake during E-LTP and L-LTP indicate that different functions and/or sites may exist for the changes in glutamate uptake during E-LTP and L-LTP.
Key words: LTP; glutamate transporters; EAAC1; GLT1a; plasticity; second messengers; signaling pathways; hippocampus
Received Dec. 28, 2005; revised Aug. 30, 2006; accepted Aug. 30, 2006.
Correspondence should be addressed to Arnold Eskin, Department of Biology and Biochemistry, University of Houston, 369 Science & Research II, Houston, TX 77204-5001. Email: eskin{at}uh.edu
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