2013 Fiscal Year Annual Research Report
Identifying a microendophenotype of post-traumatic stress disorder
Publicly Offered Research
| Project Area | Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels. |
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| Project/Area Number |
25116531
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
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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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | anxiety disorders / periaqueductal gray / amygdala / PTSD / prediction error / fear / associative learning / memory |
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| Research Abstract |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We have made progress as planned thus far
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| Strategy for Future Research Activity |
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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