Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake

Chih Hao Yang, Chiung Chun Huang, Kuei Sen Hsu

研究成果: 雜誌貢獻文章

138 引文 (Scopus)

摘要

Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1- (propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.
原文英語
頁(從 - 到)4288-4293
頁數6
期刊Journal of Neuroscience
25
發行號17
DOIs
出版狀態已發佈 - 四月 27 2005
對外發佈Yes

指紋

Glutamic Acid
N-Methyl-D-Aspartate Receptors
Hippocampal CA1 Region
Neurotransmitter Receptor
Neuronal Plasticity
Glucocorticoid Receptors
N-Methylaspartate
Baths
Hippocampus
benzyloxyaspartate

ASJC Scopus subject areas

  • Neuroscience(all)

引用此文

Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake. / Yang, Chih Hao; Huang, Chiung Chun; Hsu, Kuei Sen.

於: Journal of Neuroscience, 卷 25, 編號 17, 27.04.2005, p. 4288-4293.

研究成果: 雜誌貢獻文章

@article{6fa17e33be70499f8cdc7b077142a378,
title = "Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake",
abstract = "Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1- (propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.",
keywords = "Glucocorticoid receptor, Glutamate transporter, Hippocampus, Long-term depression, NMDA receptor, Stress",
author = "Yang, {Chih Hao} and Huang, {Chiung Chun} and Hsu, {Kuei Sen}",
year = "2005",
month = "4",
day = "27",
doi = "10.1523/JNEUROSCI.0406-05.2005",
language = "English",
volume = "25",
pages = "4288--4293",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "17",

}

TY - JOUR

T1 - Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake

AU - Yang, Chih Hao

AU - Huang, Chiung Chun

AU - Hsu, Kuei Sen

PY - 2005/4/27

Y1 - 2005/4/27

N2 - Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1- (propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.

AB - Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1- (propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.

KW - Glucocorticoid receptor

KW - Glutamate transporter

KW - Hippocampus

KW - Long-term depression

KW - NMDA receptor

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=18244394794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244394794&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0406-05.2005

DO - 10.1523/JNEUROSCI.0406-05.2005

M3 - Article

C2 - 15858055

AN - SCOPUS:18244394794

VL - 25

SP - 4288

EP - 4293

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 17

ER -