Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity

Chien Chung Chen, Chih Hao Yang, Chiung Chun Huang, Kuei Sen Hsu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The mossy fiber synapses onto hippocampal CA3 neurons show unique molecular features and a wide dynamic range of plasticity. Although acute stress has been well recognized to alter bidirectional long-term synaptic plasticity in the hippocampal CA1 region and dentate gyrus, it remains unclear whether the same effect may also occur at the mossy fiber-CA3 synapses. Here, we report that hippocampal slices prepared from adult mice that had experienced an acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) induced by high-frequency stimulation or adenylyl cyclase activator forskolin. This effect was prevented when animals were submitted to bilateral adrenalectomy or given the glucocorticoid receptor antagonist RU38486 before experiencing stress. In contrast, stress has no effect on synaptic potentiation induced by the non-hydrolysable and membrane-permeable cyclic adenosine 5′-monophosphate (cAMP) analog Sp-8-bromo-cAMPS. No obvious differences were observed between control and stressed mice in the basal synaptic transmission, paired-pulse facilitation, or frequency facilitation at the mossy fiber-CA3 synapses. We also found that the inhibitory effect of stress on mossy fiber LTP was obviated by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine, the non-specific phosphodiesterase (PDE) inhibitor 3-isobutyl-methylxanthine, and the specific PDE4 inhibitor 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone. In addition, stress induces a sustained and profound increase in cAMP-specific PDE4 activity. These results suggest that the inhibition of mossy fiber LTP by acute stress treatment seems originating from a corticosterone-induced sustained increase in the PDE4 activity to accelerate the metabolism of cAMP to adenosine, in turn triggering an adenosine A 1 receptor-mediated impairment of transmitter release machinery.

Original languageEnglish
Pages (from-to)1605-1617
Number of pages13
JournalNeuropsychopharmacology
Volume35
Issue number7
DOIs
Publication statusPublished - Jun 2010
Externally publishedYes

Fingerprint

Hippocampal Mossy Fibers
Type 4 Cyclic Nucleotide Phosphodiesterase
Long-Term Potentiation
Cyclic AMP
Adenosine
Synapses
Phosphodiesterase 4 Inhibitors
Hippocampal CA1 Region
Neuronal Plasticity
Phosphodiesterase Inhibitors
Adrenalectomy
Glucocorticoid Receptors
Dentate Gyrus
Colforsin
Corticosterone
Adenylyl Cyclases
Synaptic Transmission
Tail
Shock
Neurons

Keywords

  • Adenosine
  • CAMP
  • Long-term potentiation
  • Mossy fiber
  • Phosphodiesterase
  • Stress

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity. / Chen, Chien Chung; Yang, Chih Hao; Huang, Chiung Chun; Hsu, Kuei Sen.

In: Neuropsychopharmacology, Vol. 35, No. 7, 06.2010, p. 1605-1617.

Research output: Contribution to journalArticle

@article{0022453c1d7046fa9e9e76daed8aa38f,
title = "Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity",
abstract = "The mossy fiber synapses onto hippocampal CA3 neurons show unique molecular features and a wide dynamic range of plasticity. Although acute stress has been well recognized to alter bidirectional long-term synaptic plasticity in the hippocampal CA1 region and dentate gyrus, it remains unclear whether the same effect may also occur at the mossy fiber-CA3 synapses. Here, we report that hippocampal slices prepared from adult mice that had experienced an acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) induced by high-frequency stimulation or adenylyl cyclase activator forskolin. This effect was prevented when animals were submitted to bilateral adrenalectomy or given the glucocorticoid receptor antagonist RU38486 before experiencing stress. In contrast, stress has no effect on synaptic potentiation induced by the non-hydrolysable and membrane-permeable cyclic adenosine 5′-monophosphate (cAMP) analog Sp-8-bromo-cAMPS. No obvious differences were observed between control and stressed mice in the basal synaptic transmission, paired-pulse facilitation, or frequency facilitation at the mossy fiber-CA3 synapses. We also found that the inhibitory effect of stress on mossy fiber LTP was obviated by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine, the non-specific phosphodiesterase (PDE) inhibitor 3-isobutyl-methylxanthine, and the specific PDE4 inhibitor 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone. In addition, stress induces a sustained and profound increase in cAMP-specific PDE4 activity. These results suggest that the inhibition of mossy fiber LTP by acute stress treatment seems originating from a corticosterone-induced sustained increase in the PDE4 activity to accelerate the metabolism of cAMP to adenosine, in turn triggering an adenosine A 1 receptor-mediated impairment of transmitter release machinery.",
keywords = "Adenosine, CAMP, Long-term potentiation, Mossy fiber, Phosphodiesterase, Stress",
author = "Chen, {Chien Chung} and Yang, {Chih Hao} and Huang, {Chiung Chun} and Hsu, {Kuei Sen}",
year = "2010",
month = "6",
doi = "10.1038/npp.2010.33",
language = "English",
volume = "35",
pages = "1605--1617",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity

AU - Chen, Chien Chung

AU - Yang, Chih Hao

AU - Huang, Chiung Chun

AU - Hsu, Kuei Sen

PY - 2010/6

Y1 - 2010/6

N2 - The mossy fiber synapses onto hippocampal CA3 neurons show unique molecular features and a wide dynamic range of plasticity. Although acute stress has been well recognized to alter bidirectional long-term synaptic plasticity in the hippocampal CA1 region and dentate gyrus, it remains unclear whether the same effect may also occur at the mossy fiber-CA3 synapses. Here, we report that hippocampal slices prepared from adult mice that had experienced an acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) induced by high-frequency stimulation or adenylyl cyclase activator forskolin. This effect was prevented when animals were submitted to bilateral adrenalectomy or given the glucocorticoid receptor antagonist RU38486 before experiencing stress. In contrast, stress has no effect on synaptic potentiation induced by the non-hydrolysable and membrane-permeable cyclic adenosine 5′-monophosphate (cAMP) analog Sp-8-bromo-cAMPS. No obvious differences were observed between control and stressed mice in the basal synaptic transmission, paired-pulse facilitation, or frequency facilitation at the mossy fiber-CA3 synapses. We also found that the inhibitory effect of stress on mossy fiber LTP was obviated by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine, the non-specific phosphodiesterase (PDE) inhibitor 3-isobutyl-methylxanthine, and the specific PDE4 inhibitor 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone. In addition, stress induces a sustained and profound increase in cAMP-specific PDE4 activity. These results suggest that the inhibition of mossy fiber LTP by acute stress treatment seems originating from a corticosterone-induced sustained increase in the PDE4 activity to accelerate the metabolism of cAMP to adenosine, in turn triggering an adenosine A 1 receptor-mediated impairment of transmitter release machinery.

AB - The mossy fiber synapses onto hippocampal CA3 neurons show unique molecular features and a wide dynamic range of plasticity. Although acute stress has been well recognized to alter bidirectional long-term synaptic plasticity in the hippocampal CA1 region and dentate gyrus, it remains unclear whether the same effect may also occur at the mossy fiber-CA3 synapses. Here, we report that hippocampal slices prepared from adult mice that had experienced an acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) induced by high-frequency stimulation or adenylyl cyclase activator forskolin. This effect was prevented when animals were submitted to bilateral adrenalectomy or given the glucocorticoid receptor antagonist RU38486 before experiencing stress. In contrast, stress has no effect on synaptic potentiation induced by the non-hydrolysable and membrane-permeable cyclic adenosine 5′-monophosphate (cAMP) analog Sp-8-bromo-cAMPS. No obvious differences were observed between control and stressed mice in the basal synaptic transmission, paired-pulse facilitation, or frequency facilitation at the mossy fiber-CA3 synapses. We also found that the inhibitory effect of stress on mossy fiber LTP was obviated by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine, the non-specific phosphodiesterase (PDE) inhibitor 3-isobutyl-methylxanthine, and the specific PDE4 inhibitor 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone. In addition, stress induces a sustained and profound increase in cAMP-specific PDE4 activity. These results suggest that the inhibition of mossy fiber LTP by acute stress treatment seems originating from a corticosterone-induced sustained increase in the PDE4 activity to accelerate the metabolism of cAMP to adenosine, in turn triggering an adenosine A 1 receptor-mediated impairment of transmitter release machinery.

KW - Adenosine

KW - CAMP

KW - Long-term potentiation

KW - Mossy fiber

KW - Phosphodiesterase

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=77952415052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952415052&partnerID=8YFLogxK

U2 - 10.1038/npp.2010.33

DO - 10.1038/npp.2010.33

M3 - Article

C2 - 20237461

AN - SCOPUS:77952415052

VL - 35

SP - 1605

EP - 1617

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 7

ER -