title: A critical role of glutamate transporter type 3 in the learning and memory of mice.
abstract: Hippocampus-dependent learning and memory are associated with trafficking of excitatory amino acid transporter type 3 (EAAT3) to the plasma membrane. To assess whether this trafficking is an intrinsic component of the biochemical responses underlying learning and memory, 7- to 9-week old male EAAT3 knockout mice and CD-1 wild-type mice were subjected to fear conditioning. Their hippocampal CA1 regions, amygdalae and entorhinal cortices were harvested before, or 30 min or 3 h after the fear conditioning stimulation. We found that EAAT3 knockout mice had worse contextual and tone-related learning and memory than did the wild-type mice. The expression of EAAT3, glutamate receptor (GluR)1 and GluR2 in the plasma membrane and of phospho-GluR1 (at Ser 831) and phospho-CaMKII in the hippocampus of the wild-type mice was increased at 30 min after the fear conditioning stimulation. Similar biochemical changes occurred in the amygdala. Fear conditioning also increased the expression of c-Fos and activity-regulated cytoskeleton-associated protein (Arc) in the CA1 regions and of Arc in the entorhinal cortices of the wild-type mice. These biochemical responses were attenuated in the EAAT3 knockout mice. These results suggest that EAAT3 plays a critical role in learning and memory. Our results also provide initial evidence that EAAT3 may have receptor-like functions to participate in the biochemical reactions underlying learning and memory.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology and Pain Management, Seoul National University Bundang Hospital, Bundang-Gu, Seongnam, Republic of Korea.
authors.forename: Sang-Hon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Operating Room, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D003214:Conditioning, Classical / Q000502:physiology; D004597:Electroshock; D018728:Entorhinal Cortex / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism*; D005239:Fear / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation
chemical_list: D050580:Excitatory Amino Acid Transporter 3
keywords: AMPA receptor; Glutamate transporters; Learning and memory