Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity.
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.
Chen
Chien-Chung
CC
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yang
Chih-Hao
CH
Huang
Chiung-Chun
CC
Hsu
Kuei-Sen
KS
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D055592:Biophysical Phenomena / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood; D000242:Cyclic AMP / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives; D013315:Stress, Psychological / Q000473:pathology* / Q000517:prevention & control; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000451:Mineralocorticoid Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; D005576:Colforsin; D013148:Spironolactone; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C041006:RU 28318; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003345:Corticosterone