Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory
Autor: | Ya Hsin Hsiao, Hui Chi Hung, Po Wu Gean |
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Rok vydání: | 2015 |
Předmět: |
Male
Methylazoxymethanol Acetate Neurogenesis Subventricular zone Antimitotic Agents Biology Extinction Psychological Subgranular zone Random Allocation chemistry.chemical_compound Memory medicine Animals Hedgehog Proteins Pharmacology (medical) Fear conditioning Sonic hedgehog Biological Psychiatry Nucleic Acid Synthesis Inhibitors Neurons Pharmacology Methylazoxymethanol acetate Cytarabine Fear social sciences Amygdala medicine.disease humanities Cell biology Mice Inbred C57BL Psychiatry and Mental health medicine.anatomical_structure nervous system Neurology chemistry Extinction (neurology) Auditory Perception biology.protein Neurology (clinical) NeuN Neuroscience Signal Transduction |
Zdroj: | European Neuropsychopharmacology. 25:1723-1732 |
ISSN: | 0924-977X |
DOI: | 10.1016/j.euroneuro.2015.07.005 |
Popis: | It is now recognized that neurogenesis occurs throughout life predominantly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. In the present study, we investigated the relationship between neurogenesis in the amygdala and extinction of fear memory. Mice received 15 tone-footshock pairings. Twenty-four hours after training, the mice were given 15 tone-alone trials (extinction training) once per day for 7 days. Two hours before extinction training, the mice were injected intraperitoneally with 5-bromo-3-deoxyuridine (BrdU). BrdU-positive and NeuN-positive cells were analyzed 52 days after the training. A group of mice that received tone-footshock pairings but no extinction training served as controls (FC+No-Ext). The number of BrdU(+)/NeuN(+) cells was significantly higher in the extinction (FC+Ext) than in the FC+No-Ext mice. Proliferation inhibitor methylazoxymethanol acetate (MAM) or DNA synthesis inhibitor cytosine arabinoside (Ara-C) reduced neurogenesis and retarded extinction. Silencing Sonic hedgehog (Shh) gene with short hairpin interfering RNA (shRNA) by means of a retrovirus expression system to knockdown Shh specifically in the mitotic neurons reduced neurogenesis and retarded extinction. By contrast, over-expression of Shh increased neurogenesis and facilitated extinction. These results suggest that amygdala neurogenesis and Shh signaling are involved in the extinction of fear memory. |
Databáze: | OpenAIRE |
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