Kong Mi-Seon, Jo Yong S, Sethi Ekayana, Pyeon Gyeong Hee, Zweifel Larry S
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle WA USA.
School of Psychology, Korea University, Seoul, Republic of Korea.
bioRxiv. 2024 Sep 8:2024.09.05.611495. doi: 10.1101/2024.09.05.611495.
A positive mental state has been shown to modulate fear-related emotions associated with the recall of fear memories. These, and other observations suggest the presence of central brain mechanisms for affective states to interact. The neurotransmitter dopamine is important for both Reward- and fear-related processes, but it is unclear whether dopamine contributes to such affective interactions. Here, we show that precisely timed Reward-induced activation of dopamine neurons in mice potently modifies fear memories and enhances their extinction. This Reward-based switch in fear states is associated with changes in dopamine release and dopamine-dependent regulation of fear encoding in the central amygdala (CeA). These data provide a central mechanism for Reward-induced modification of fear states that have broad implications for treating generalized fear disorders.
积极的心理状态已被证明可调节与恐惧记忆回忆相关的恐惧情绪。这些以及其他观察结果表明,存在中枢脑机制使情感状态相互作用。神经递质多巴胺对奖赏和恐惧相关过程都很重要,但尚不清楚多巴胺是否促成这种情感相互作用。在此,我们表明,精确计时的奖赏诱导小鼠多巴胺神经元激活可有效改变恐惧记忆并增强其消退。这种基于奖赏的恐惧状态转换与多巴胺释放的变化以及中央杏仁核(CeA)中恐惧编码的多巴胺依赖性调节有关。这些数据为奖赏诱导的恐惧状态改变提供了一种中枢机制,对治疗广泛性恐惧障碍具有广泛意义。