内侧缰核胆碱能神经元GABAB受体通过突触前兴奋作用调控动物恐惧记忆  

Presynaptic Excitation via GABA_B Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression

作　　者：张举恩 Lubin Tan Yuqi Ren Jingwen Liang Rui Lin Qiru Feng Jingfeng Zhou Fei Hu Jing Ren Chao Wei Tao Yu Yinghua Zhuang Bernhard Bettler Fengchao Wang 罗敏敏 

机构地区：[1]北京生命科学研究所 [2]清华大学 [3]清华大学生命科学学院

出　　处：《科学新闻》2017年第4期38-38,共1页Science News

基　　金：科技部973;国家自然科学基金委;北京市政府资助

摘　　要：动物的生存依赖于将预警信号和危险联系起来．对预警信号形成恐惧记忆，以便提前做出反应。当预警信号不再与危险相关时，动物逐渐解除这种联系，消退恐惧记忆，以适应新的生存环境。恐惧记忆消退缺陷被认为和人类创伤后应激障碍（PTSD）等精神障碍有紧密关系。目前关于动物恐惧记忆的研究主要集中在杏仁核及其相关脑区。Fear behaviors are regulated by adaptive mechanisms that dampen their expression in the absence of danger. By studying circuits and the molecular mechanisms underlying this adaptive response, we show that cholinergic neurons of the medial habenula reduce fear memory expression through GABA_B presynaptic excitation. Ablating these neurons or inactivating their GABA_B receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABA_B receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABA_B mediates excitation by amplifying presynaptic Ca²⁺ entry through Ca_v2.3 channels and potentiating co-release of glutamate, acetylcholine, and neurokinin B to excite interpeduncular neurons. Activating the receptors for these neurotransmitters or enhancing neurotransmission with a phosphodiesterase inhibitor reduces fear responses of both wild-type and GABA_B mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABA_B receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders.

关 键 词：记忆 恐惧 动物 神经元 创伤后应激障碍 兴奋 突触 受体 

分 类 号：Q95[生物学—动物学]