청각 피질의 전기 자극을 조건 자극으로 사용한 공포 기억 유도 = Conditioned fear response induced by electrical brain stimulation of the auditory cortex as a conditioned stimulus

다국어 초록 (Multilingual Abstract)

Auditory fear memory is represented as long-lasting changes in the two input pathways into the lateral nucleus of the amygdala (LA): thalamo-amygdala and thalamo-cortico-amygdala pathways. Previously in our laboratory, we have shown that plasticity in the thalamo-amygdala pathway is critical for fear memory formation when electrical stimulation of the medial division of the medial geniculate nucleus of the thalamus (MGm) was used as the conditioned stimulus (CS). This short-circuit approach with the electrical brain stimulation as the CS (eCS) allowed us to test the efficacy of a particular pathway of interest without involving other sensory pathways. In the current study, we tested whether synaptic plasticity in the cortical pathway could support fear memory formation in rats by pairing the electrical stimulation of the secondary auditory cortex (Te3) with the footshock unconditioned stimulus (US). Following six paired presentations of the eCS and US, rats in the Te3-paired group showed significant level of freezing in the eCS-only test session, compared to a group that received unpaired presentations of the eCS and US. In addition, we also included MGm-paired group that received paired presentation of the MGm stimulation and US. The level of freezing to the eCS in the test session was comparable between Te3- and MGm-paired group. To examine the long-term maintenance of conditioned fear memory, freezing was measured 3 weeks after the acquisition session with the eCS. Both MGm-paired and Te3-paired groups showed considerable level of freezing and there was no significant difference between the two groups. In conclusion, both thalamic and cortical input pathways into the amygdala effectivly support fear conditioning when brain stimulation was used as the CS, suggesting that learning-induced changes in either the thalamo-amygdala or the cortico-amygdala synapse might be sufficient for storing fear memory.

국문 초록 (Abstract)

연합기억형성에 따른 시냅스 가소성을 규명하기 위한 많은 연구들이 파블로프 공포 조건화를 사용하여 왔다. 특히 청각 자극에 의해 형성되는 공포 기억은 편도체 외측핵(lateral nucleus of the amygdala, LA)으로 투사하는 두 가지 입력 경로에서의 변화로 나타난다. 이 두 입력 경로는 각각 시상-편도체 경로(thalamo-amygdala pathway)와 피질-편도체 경로(cortico-amygdala pathway)이다. 본 연구실의 과거 연구는 시상의 청각핵(medial geniculate nucleus: MGm) 전기 자극을 조건 자극으로 사용하여 조건화를 유도하고 이에 따른 시상-편도체 경로의 시냅스 효율성 증가를 보고하였다. 따라서 본 연구에서는 피질-편도체 경로의 가소성을 확인하기 위한 연구의 일환으로 이 경로의 전기 자극을 조건자극으로 사용한 공포 조건화가 행동적인 공포 반응을 유도할 수 있는지 여부를 확인하였다. 쥐(rat)를 이용하여 이차 청각 피질(secondary auditory cortex, Te3)의 뇌내 전기 자극을 조건 자극(electrical conditioned stimulus, eCS)으로, 발바닥 전기 자극을 무조건 자극(unconditioned stimulus, US)으로 사용하여 공포조건화(Conditioning)를 실시하였다. 조건화 다음날은 eCS만을 3회 제시하는 기억력 검사(Test)를 실시하여 조건화된 공포반응(conditioned response: CR)으로서 동결반응(freezing)을 측정하였다. 그 결과, eCS와 US를 짝지어 제시한 집단들(Te3-paired 및 MGm-paired)이 두 자극을 무선적으로 제시한 집단(Te3-unpaired)보다 eCS에 대해 더 많은 동결반응을 보였다. 또한 피질-편도체 경로 자극을 짝지어 제시한 집단(Te3-paired)의 동결반응 수준은 시상-편도체 경로 자극을 동일한 횟수만큼 짝지어 제시한 집단(MGm-paired)과 비교해봤을 때, 유의미한 차이가 없었다. 이러한 조건반응은 3주 후 기억력 검사(Retest)에서도 유지되었다. 이 결과를 고려했을 때, eCS를 사용하는 경우 피질-편도체 경로의 가소성만으로도 공포기억의 저장이 가능하며 이러한 공포기억은 외부 감각 자극을 사용하여 조건화시킨 경우와 유사한 행동적 특성을 지닌다.

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