Document Detail


The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.
MedLine Citation:
PMID:  17081505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized.
METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation.
RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning.
CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.
Authors:
Surojit Paul; Peter Olausson; Deepa V Venkitaramani; Irina Ruchkina; Timothy D Moran; Natalie Tronson; Evan Mills; Shawn Hakim; Michael W Salter; Jane R Taylor; Paul J Lombroso
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-01
Journal Detail:
Title:  Biological psychiatry     Volume:  61     ISSN:  0006-3223     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-16     Completed Date:  2007-06-06     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1049-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acoustic Stimulation
Aminoacetonitrile / analogs & derivatives,  pharmacology
Amygdala / physiology*
Animals
Behavior, Animal / drug effects
Cells, Cultured
Conditioning, Classical / physiology
Cycloheximide / pharmacology
Electric Stimulation
Enzyme Inhibitors / pharmacology
Fear / physiology*
Female
Immunohistochemistry
Long-Term Potentiation / physiology*
Memory / physiology*
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors,  metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors,  metabolism
Neostriatum / metabolism,  physiology*
Patch-Clamp Techniques
Point Mutation / genetics,  physiology
Pregnancy
Protein Synthesis Inhibitors / pharmacology
Protein Tyrosine Phosphatases / genetics,  metabolism,  physiology*
Rats
Rats, Sprague-Dawley
Translocation, Genetic / physiology
Grant Support
ID/Acronym/Agency:
DA017360/DA/NIDA NIH HHS; DA15222/DA/NIDA NIH HHS; K02 MH001527/MH/NIMH NIH HHS; MH01527/MH/NIMH NIH HHS; MH52711/MH/NIMH NIH HHS; R01 DA017366/DA/NIDA NIH HHS; R01 MH052711/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Protein Synthesis Inhibitors; 0/SL 327; 3739OQ10IJ/Aminoacetonitrile; 98600C0908/Cycloheximide; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.1.3.48/Protein Tyrosine Phosphatases
Comments/Corrections

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