title: Dynamic expression of FKBP5 in the medial prefrontal cortex regulates resiliency to conditioned fear.
abstract: 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.
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: Marangelie
authors.initials: M
authors.lastname: Criado-Marrero
authors.affiliation: Department of Biology, University of Puerto Rico-Ponce, Ponce 00734, Puerto Rico.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Morales Silva
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: Bethzaly
authors.initials: B
authors.lastname: Velazquez
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: Anixa
authors.initials: A
authors.lastname: Hernández
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: María
authors.initials: M
authors.lastname: Colon
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cruz
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: Omar
authors.initials: O
authors.lastname: Soler-Cedeño
authors.affiliation: Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.
authors.forename: James T
authors.initials: JT
authors.lastname: Porter
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000099159:Tacrolimus Binding Protein 5
chemical_list: D049452:Green Fluorescent Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5