| 研究領域 | マイクロエンドフェノタイプによる精神病態学の創出 |
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| 研究課題/領域番号 |
25116531
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| 研究種目 |
新学術領域研究(研究領域提案型)
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| 研究機関 | 独立行政法人理化学研究所 |
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研究代表者 |
JOHANSEN JOSHUA 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (80625351)
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| 研究期間 (年度) |
2013-04-01 – 2015-03-31
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| キーワード | anxiety disorders / periaqueductal gray / amygdala / PTSD / prediction error / fear / associative learning / memory |
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| 研究概要 |
We have made significant progress in Heisei 25 in delineating a circuit mechanism for how fear learning levels are set. Fear learning reaches an asymptote beyond which no further learning occurs and this asymptote is dependent on the intensity of the aversive experience. We have found that prediction error coding in lateral amygdala (LA) neurons is important in setting this learning asysmptote. Intriguingly, we also discovered that a projection from the central nucleus of the amygdala (CE) to the periaqueductal gray (PAG) is important in controlling prediction error coding in LA neurons and setting behavioral fear learning asymptotes. We used optogenetic manipulations to inhibit CE input terminals in PAG during fear conditioning and found that this manipulation reengaged prediction error coding in LA neurons and increased learning levels much like increasing the aversive intensity. Thus we have discovered a circuit mechanism which produces amplified fear memories. This may have important clinical implications for the treatment of anxiety disorders, such as PTSD. which are characterized by exaggerated aversive learning.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have made progress as planned thus far
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| 今後の研究の推進方策 |
In the coming year we will examine the effect of manipulating CE-PAG input terminals on local microcircuit processing within different subregions of the PAG and determine whether these manipulations produce an anxiety like behavioral phenotype.
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