title: PARP-1 activity is required for the reconsolidation and extinction of contextual fear memory.
abstract: BACKGROUND
  Memory consolidation, reconsolidation, and extinction have been shown to require new gene expression. Poly ADP-ribosylation mediated by poly (ADP-ribose) polymerase-1 (PARP-1) is known to regulate transcription through histone modification. Recent studies have suggested that PARP-1 positively regulates the formation of long-term memory (LTM); however, the roles of PARP-1 in memory processes, especially processes after retrieval, remain unknown.
  
  
  RESULTS
  Here, we show critical roles for PARP-1 in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of PARP-1 activity in the hippocampus or medial prefrontal cortex (mPFC) on these memory processes. Similarly with previous findings, a micro-infusion of the PARP-1 inhibitor 3-aminobenzamide or PJ34 into the dorsal hippocampus, but not mPFC, impaired LTM formation without affecting short-term memory (STM). Importantly, this pharmacological blockade of PARP-1 in the dorsal hippocampus, but not mPFC, also disrupted post-reactivation LTM without affecting post-reactivation STM. Conversely, micro-infusion of the PARP-1 inhibitors into the mPFC, but not dorsal hippocampus, blocked long-term extinction. Additionally, systemic administration of the PARP-1 inhibitor Tiq-A blocked c-fos induction in the hippocampus, which is observed when memory is consolidated or reconsolidated, and also blocked c-fos induction in the mPFC, which is observed when memory is extinguished.
  
  
  CONCLUSIONS
  Our observations showed that PARP-1 activation is required for the consolidation, reconsolidation, and extinction of contextual fear memory and suggested that PARP-1 contributes to the new gene expression necessary for these memory processes.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan. 44312002@nodai.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Inaba
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan. r_new_2000@yahoo.co.jp.
authors.forename: Akinori
authors.initials: A
authors.lastname: Tsukagoshi
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan. kida@nodai.ac.jp.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, 332-0012, Japan. kida@nodai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D011065:Poly(ADP-ribose) Polymerases