사전 경험에 따라 편도체에서 부신피질 자극호르몬 방출인자를 분비하는 뉴런들이 행동에 미치는 영향 = Corticotropin Releasing Factor-Producing Neurons in the Central Amygdala Induces Experience-Dependent Influences on Behavior*

다국어 초록 (Multilingual Abstract)

The central nucleus of the amygdala (CeA) contains a group of cells that produce a neuropeptide, corticotropin releasing factor (CRF). The literature suggests that CRF in the CeA has a negative effect on behavior, such as increased anxiety and fear. However recent studies reported a conflicting result showing a rewarding effect of CRF. To understand how CRF lead to different behavioral effects, CRF neurons in the CeA were genetically manipulated to express a light-activated cation channel, channelrhodopsin-2, using CRF-cre mice. When the animals were initially tested to press a lever for light delivery in an operant conditioning (OP) and to visit one of two compartment for light presentation in a real-time place preference task (RTPP), CRF activation did not alter animals’ behavior at all. Stimulation of CRF neurons also failed to change animals’ anxiety levels compared to their control group in an elevated plus maze (EPM). After experiencing a lever press for food rewards for 5 days, however, CRF activation in the same mice induced rewarding effects in both OP and RTPP. Using a different set of mice, it was also examined whether CRF activation after forming fear memory resulted in negative effects on behavior. Indeed, CRF activation did not produce any effects before fear conditioning, but the same manipulation significantly elevated anxiety levels in EPM and induced aversive effects in RTPP after fear conditioning. These results demonstrate that CRF neurons can exert either positive or negative impacts on behavior depending on prior experiences.

국문 초록 (Abstract)

편도체내에는 부신피질 자극호르몬 방출인자(corticotropin releasing factor, 이하 CRF)를 분비하는 뉴런들이 존재한다. 기존에는 CRF이 방출되면 불안 및 공포와 같은 부정적 행동결과를 초래한다고 알려져 있었으나, 최근 보상효과를 일으킨다는 상반된 주장이 제기되고 있다. 본 연구에서는 사전 경험에 따라서 CRF뉴런들의 활성화 효과가 달라질 수 있다는 가설을 검증하기 위해서 동물실험을 진행하였다. 유전자변형 동물들을 이용하여 광유전학적으로 편도체내의 CRF뉴런들을 선택적으로 활성화할 수 있도록 조작하였다. 사전에 특별한 경험이 없는 상태에서 CRF뉴런들을 활성화하였을 경우 통제집단과 비교해서 행동반응에 유의미한 차이가 관찰되지 않았다. 그러나 먹이 보상물을 이용한 도구적 조건화 훈련을 마친 뒤에 CRF뉴런들을 활성화하였을 때에는 이전 행동을 지속하게 만드는 보상효과를 유발하였다. 새로운 집단의 동물들을 대상으로 공포조건화 전후로 CRF활성화가 행동에 미치는 영향도 실험하였다. 공포를 경험하기 전에는 나타나지 않았으나, 공포기억을 형성한 후에 CRF뉴런들을 활성화하면 불안 및 기피행동을 관찰 할 수 있었다. 이러한 실험결과들은 사전 경험에 따라서 행동에 미치는 CRF의 영향이 달라지는 것을 보여준다. 따라서 편도체의 CRF뉴런들은 정서가치를 표상하는 것이 아니라, 최근에 형성한 경험 및 기억이 더 발현되도록 유도하는 기능을 하는 것으로 판단된다.

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