title: Learning induces sonic hedgehog signaling in the amygdala which promotes neurogenesis and long-term memory formation.
abstract: BACKGROUND
  It is known that neurogenesis occurs throughout the life mostly in the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle. We investigated whether neurogenesis occurred in the amygdala and its function in fear memory formation.
  
  
  METHODS
  For detection of newborn neurons, mice were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU) 2h before receiving 15 tone-footshock pairings, and newborn neurons were analyzed 14 and 42 days after training. To determine the relationship between neurogenesis and memory formation, mice were given a proliferation inhibitor methylazoxymethanol (MAM) or a DNA synthesis inhibitor cytosine arabinoside (Ara-C). To test whether sonic hedgehog (Shh) signaling was required for neurogenesis, Shh-small hairpin-interfering RNA (shRNA) was inserted into a retroviral vector (Retro-Shh-shRNA).
  
  
  RESULTS
  The number of BrdU(+)/Neuronal nuclei (NeuN)(+) cells was significantly higher in the conditioned mice, suggesting that association of tone with footshock induced neurogenesis. MAM and Ara-C markedly reduced neurogenesis and impaired fear memory formation. Shh, its receptor patched 1 (Ptc1), and transcription factor Gli1 protein levels increased at 1 day and returned to baseline at 7 days after fear conditioning. Retro-Shh-shRNA, which knocked down Shh specifically in the mitotic neurons, reduced the number of BrdU(+)/NeuN(+) cells and decreased freezing responses.
  
  
  CONCLUSIONS
  These results suggest that fear learning induces Shh signaling activation in the amygdala, which promotes neurogenesis and fear memory formation.
authors.affiliation: Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan (Drs Hung, Hsaio, and Gean).
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan (Drs Hung, Hsaio, and Gean).
authors.forename: Ya-Hsin
authors.initials: YH
authors.lastname: Hsiao
authors.affiliation: Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan (Drs Hung, Hsaio, and Gean). powu@mail.ncku.edu.tw.
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001973:Bromodeoxyuridine; D003214:Conditioning, Classical / Q000502:physiology*; D003561:Cytarabine / Q000494:pharmacology; D004597:Electroshock; D005106:Exploratory Behavior; D005239:Fear / Q000523:psychology; D053823:Hedgehog Proteins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017774:Long-Term Potentiation; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D007166:Immunosuppressive Agents; D034741:RNA, Small Interfering; D003561:Cytarabine; D008746:Methylazoxymethanol Acetate; D001973:Bromodeoxyuridine; C030667:methylazoxymethanol
keywords: amygdala; fear memory; neurogenesis; sonic hedgehog