- P-ISSN1226-9654
- E-ISSN2733-466X
- KCI
변연전영역의 전기적 손상이 맥락-의존적 변별 공포조건화에 미치는 영향
Effects of Electrolytic Lesion of the Prelimbic Area on Context-dependent Fear Discrimination in Rats
김현택 (고려대학교)
최준식 (고려대학교)
권정태 (고려대학교)
김남수 (고려대학교)
초록
최근, 전전두피질(medial prefrontal cortex: mPFC)이 적절한 상황에서 공포반응의 표현을 조절하도록 하는 데 관여할 것이라는 제안이 제기되고 있다. 본 연구에서는 mPFC의 하부영역인 변연전영역(prelimbic area: PL)이 맥락을 이용하여 공포반응의 유발을 조절하는 데 어떤 영향을 미치는지 살펴보고자 하였다. 이러한 가설적인 PL의 역할을 검증하기 위해, 본 연구에서는 불확실한 갈등 상황을 제공하여 동물이 맥락에 따라 적절한 반응을 해야 하는 맥락-의존적 변별 공포조건화 패러다임을 적용하였다. 즉, 두 가지 맥락과 한 가지 CS를 사용하여 한 맥락에서는 CS와 US가 연합되고, 다른 맥락에서는 CS만 제시되어 맥락에 따라 CS의 의미가 달라지는 조건을 구성하였다. 4일간의 변별 공포학습 훈련 후 절반의 동물에 대해서는 PL을 손상시키고, 나머지 절반에 대해서는 모의 시술을 실시하였다. 회복기간 후 변별 공포학습 수행을 검사한 결과, 모의손상 동물이 두 맥락에서 CS에 대한 반응을 다르게 보인 것과는 달리, PL 손상 동물은 두 맥락에서 CS에 대한 반응에 유의한 차이가 없었다. 이러한 결과는 PL의 손상이 맥락 정보를 이용해야 하는 변별학습 수행을 방해하였다는 것을 보여준다. 또한, 검사시행 후 2일 간의 추가 훈련을 받았을 때 PL 손상 동물들은 훈련 회기 동안에는 모의손상 동물과 유사한 정도로 수행을 하여, 변별 공포기억 습득 과정에서는 손상이 없는 것으로 보였다. 그러나 재훈련에 대한 재검사 시행 시 PL 손상 동물은 모의 손상 동물과는 달리 맥락에 따른 CS에 대한 반응을 다르게 보이지 않았다. 이는 PL이 동물의 동결반응의 표현 자체에는 관여하지 않으나, 맥락에 따른 변별 공포반응의 유발에는 필요함을 보여주는 것이다. 결론적으로, 본 연구의 결과는 PL이 맥락에 따라 공포 반응의 표현을 조절해야 하는 상황에서 적절하게 공포반응을 유발시키는 데 관여할 것임을 시사한다.
- keywords
- medial prefrontal cortex(mPFC), prelimbic area(PL), context, fear discrimination, freezing, 내측전전두피질, 변연전영역, 맥락, 공포변별학습, 동결반응
Abstract
Recent studies suggest that the medial prefrontal cortex (mPFC) is necessary for the contextual modulation of fear memory. This study investigated whether the prelimbic (PL) subregion of mPFC has influence on the regulation of fear response to the ambiguous CS using contextual information. To verify the hypothetical role of PL, we adopted a context-dependent discriminatory fear conditioning where context dictates CS-US contingency. Rats received 3 pairings of the CS (30-sec, 4-kHz, 75-dB tone) and the US (0.5-sec, 0.5-mA footshock) in context A followed after 1 hour by 10 CS-only trials in context B for 4 days. In the last training session, all rats showed significantly more freezing in context A than in context B. Twenty-four hours after the last training session, PL was lesioned in half of the rats. After eleven days of recovery, we tested the effects of electrolytic lesion of PL on context-dependent discriminatory fear conditioning. PL-lesioned animals showed similar responding to the CS in context A and B, whereas sham-lesioned rats show significantly different responding. This result indicates that the lesion of PL disturbed discriminatory responses to the ambiguous CS when contextual information should be used to resolve the ambiguity of the CS. When all animals were subjected to subsequent training sessions (retraining sessions) for two additional days, PL-lesioned rats acquired context-dependent discriminatory fear memory during the retraining sessions. However, when the rats were tested on the next day, PL-lesioned animals did not show the differential responding to the CS in contextual A and B. This result indicates that PL is necessary for retrieving the learned discriminatory fear memory in the appropriate context. Taken together, these findings suggest that PL might be involved in fear expression under the conditions where the fear responses must be regulated by contexts.
- keywords
- medial prefrontal cortex(mPFC), prelimbic area(PL), context, fear discrimination, freezing, 내측전전두피질, 변연전영역, 맥락, 공포변별학습, 동결반응
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