title: Proteins linked to extinction in contextual fear conditioning in the C57BL/6J mouse.
abstract: Studying fear extinction is a major topic in neuroscience. No information on systematic studies on the linkage of contextual fear conditioning (cFC) with hippocampal protein levels is available and we were therefore interested in protein differences between animals with poor and good extinction. cFC was carried out in C57BL/6J mice, hippocampi were taken and proteins were run on two-dimensional gel electrophoresis with subsequent quantification of protein spots. In-gel digestion with trypsin and identification by ion trap MS/MS (high-capacity ion trap) was used for the identification of significantly different hippocampal proteins between mice with good and poor performance of extinction. Signaling protein ras-related protein rab-7A and septin 8 levels were significantly higher in hippocampus of poor extinguishers, whereas ubiquitin carboxyterminal hydrolase isozyme L1 showed higher levels in animals with good extinction performance. A series of additional proteins showed significantly different levels between groups but the abovementioned were confirmed by immunoblotting. The abovementioned proteins have never been reported to be linked to extinction, memory, or learning and herein evidence for the involvement of several proteins in extinction mechanism as well as probably representing pharmaceutical targets is provided. Moreover, it is intriguing to demonstrate the differences between good and poor extinction performance at the protein level.
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Sanjay V
authors.initials: SV
authors.lastname: Boddul
authors.forename: Sudarshan S
authors.initials: SS
authors.lastname: Patil
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zheng
authors.forename: Gunyong
authors.initials: G
authors.lastname: An
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D003213:Conditioning, Psychological / Q000502:physiology*; D054640:Dual Specificity Phosphatase 3 / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000737:chemistry* / Q000502:physiology; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods; D040901:Proteomics / Q000379:methods; D058112:Septins / Q000378:metabolism; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D054640:Dual Specificity Phosphatase 3; D058112:Septins; D043222:Ubiquitin Thiolesterase; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C517026:Dusp3 protein, mouse; C496976:Uchl1 protein, mouse