Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment.
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.
Wong
Tak Pan
TP
Department of Medicine, Brain Research Centre, Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, BC, Canada.
Howland
John G
JG
Robillard
Julie M
JM
Ge
Yuan
Y
Yu
Wayne
W
Titterness
Andrea K
AK
Brebner
Karen
K
Liu
Lidong
L
Weinberg
Joanne
J
Christie
Brian R
BR
Phillips
Anthony G
AG
Wang
Yu Tian
YT
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*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate