title: Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment.
abstract: Acute stress impairs memory retrieval and facilitates the induction of long-term depression (LTD) in the hippocampal CA1 region of the adult rodent brain. However, whether such alterations in synaptic plasticity cause the behavioral effects of stress is not known. Here, we report that two selective inhibitors of the induction or expression of stress-enabled, N-methyl-D-aspartate receptor-dependent hippocampal LTD also block spatial memory retrieval impairments caused by acute stress. Additionally, we demonstrate that facilitating the induction of hippocampal LTD in vivo by blockade of glutamate transport mimics the behavioral effects of acute stress by impairing spatial memory retrieval. Thus, the present study demonstrates that hippocampal LTD is both necessary and sufficient to cause acute stress-induced impairment of spatial memory retrieval and provides a new perspective from which to consider the nature of cognitive deficits in disorders whose symptoms are aggravated by stress.
authors.affiliation: Department of Medicine, Brain Research Centre, Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Tak Pan
authors.initials: TP
authors.lastname: Wong
authors.forename: John G
authors.initials: JG
authors.lastname: Howland
authors.forename: Julie M
authors.initials: JM
authors.lastname: Robillard
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ge
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Titterness
authors.forename: Karen
authors.initials: K
authors.lastname: Brebner
authors.forename: Lidong
authors.initials: L
authors.lastname: Liu
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate