Effects of optogenetic activation of dopamine neurons during discriminatory fear learning

강화학습에 중요한 역할을 한다고 알려진 중뇌의 도파민 뉴런들이 전기충격과 같은 혐오자극을 이용한 학습에도 기여한다고 보고되었다. 특히 도파민 뉴런들은 혐오자극과 연합된 자극이 제시되었을 때 억제되거나 활성화되는 상이한 반응을 보인다고 알려졌다. 유전자 조작을 통해 이 두 가지 도파민 반응 중에서 혐오연합자극에 대한 활성화 반응만 선택적으로 저하시킨 동물들을 공포스러운 경험에 노출시키면, 이후 일반화된 불안행동이 유발된다고 보고되었다. 따라서 역으로 혐오연합자극을 제시하는 동안 다수의 도파민 뉴런들을 인위적으로 활성화시켜 현저성 표상을 높이면 변별 공포조건화의 학습을 향상시킬 가능성이 있다. 본 연구에서는 이 가설을 검증해 보기위해서 특정 조건자극(CS+)과 전기충격을 연합시키고 다른 자극(CS-)과는 연합시키지 않는 공포학습을 진행하는 동안 두 CS중 하나의 CS를 선택하여 해당 CS를 제시할 때 광유전학적으로 도파민 뉴런들을 활성화시켰다. 이후, CS+와 CS-만을 번갈아 제시하는 기억검사를 실시하면서 공포반응을 측정하였다. 도파민 뉴런들을 활성화시키지 않았던 통제집단은 두 CS에 동등한 수준의 동결반응을 보였으나, 도파민을 활성화시켰던 동물들은 CS-에 비해 CS+에 유의미하게 높은 공포반응을 보였다. 이러한 변별력 향상은 도파민 뉴런들이 공포 조건화 과제동안 자극 일반화에 기여함을 시사한다.

keywords: dopamine, fear conditioning, optogenetics, 도파민, 공포조건화, 광유전학

Abstract

Midbrain dopamine neurons exhibit diverse responses to aversive stimuli, such as foot and tail shocks. Specifically one group of dopamine cells is phasically inhibited by the stimuli, whereas the other group is excited. A previous report indicated that mice whose dopamine neurons were genetically modified to disrupt the excited, but not inhibited, response to a shock exhibited generalized anxiety behavior after experiencing fearful events. Thus, it was hypothesized that an increase in dopaminergic excitation improved discriminatory fear learning. To test this idea, mice were trained in a discriminatory fear conditioning paradigm where one auditory conditioned stimulus (CS+) was paired with aversive footshock and the other tone (CS-) was not paired. Dopamine neurons in the ventral tegmental area were optogenetically stimulated during the presentation of one of the two CSs. The intensity of the footshock was strong enough for control mice to show generalized fear responses to both CSs. However, dopamine-stimulated mice was able to discriminate between two CSs, so that they freezed more time in response to CS+ than to CS-. These results suggest that dopamine neurons contribute to fear discrimination.

keywords: dopamine, fear conditioning, optogenetics, 도파민, 공포조건화, 광유전학

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논문 상세

Vol.28 No.1

도파민 뉴런들의 광유전학적 활성화가 변별 공포 기억에 미치는 영향

Effects of optogenetic activation of dopamine neurons during discriminatory fear learning

초록

Abstract

참고문헌

한국심리학회지: 인지 및 생물