Dynamic expression of FKBP5 in the medial prefrontal cortex regulates resiliency to conditioned fear
| Autor: | Marangelie Criado-Marrero, Roberto J. Morales Silva, James T. Porter, Emmanuel Cruz, Anixa Hernandez, Omar Soler-Cedeño, Maria Colon, Bethzaly Velazquez |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Time Factors Cognitive Neuroscience Green Fluorescent Proteins Prefrontal Cortex Extinction Psychological Developmental psychology Rats Sprague-Dawley Tacrolimus Binding Proteins 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Conditioning Psychological Avoidance Learning Animals Medicine RNA Messenger Fear conditioning RNA Small Interfering Maze Learning Prefrontal cortex Fear processing in the brain Regulation of gene expression Analysis of Variance business.industry Research Fear Extinction (psychology) Rats 030104 developmental biology Neuropsychology and Physiological Psychology Acoustic Stimulation Gene Expression Regulation Exploratory Behavior Conditioning Analysis of variance FKBP5 business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Learning & Memory. 24:145-152 |
| ISSN: | 1549-5485 |
| DOI: | 10.1101/lm.043000.116 |
| Popis: | The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this study, we used rats as an animal model to examine whether FKBP5 in the infralimbic (IL) or prelimbic (PL) medial prefrontal cortex regulates fear conditioning or extinction. First, we examined FKBP5 expression in IL and PL during fear conditioning or extinction. In contrast to the stable expression of FKBP5 seen in PL, FKBP5 expression in IL increased after fear conditioning and remained elevated even after extinction suggesting that IL FKBP5 levels may modulate fear conditioning or extinction. Consistent with this possibility, reducing basal FKBP5 expression via local infusion of FKBP5–shRNA into IL reduced fear conditioning. Furthermore, reducing IL FKBP5, after consolidation of the fear memory, enhanced extinction memory indicating that IL FKBP5 opposed formation of the extinction memory. Our findings demonstrate that lowering FKBP5 expression in IL is sufficient to both reduce fear acquisition and enhance extinction, and suggest that lower expression of FKBP5 in the ventral medial prefrontal cortex could contribute to resiliency to PTSD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|