Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish.
Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish.
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DOI：
10.1186/s12915-018-0502-y
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发表时间：
2018-04-25
期刊：
影响因子：
5.4
通讯作者：
Kawakami K
中科院分区：
文献类型：
--
作者：
Lal P;Tanabe H;Suster ML;Ailani D;Kotani Y;Muto A;Itoh M;Iwasaki M;Wada H;Yaksi E;Kawakami K
恐惧条件反射是动物生存所必需的一种学习形式，可用作研究学习和记忆机制的行为范式。在哺乳动物中，杏仁核在恐惧调节中起着至关重要的作用。在硬骨鱼中，通过解剖学和消融研究，背侧端脑 (Dm) 的内侧区被假定为哺乳动物杏仁核的同源物，显示出在条件性回避反应中的作用。然而，通过 Dm 进行条件性回避反应所需的神经元群尚未在功能或遗传上得到定义。我们的目的是通过斑马鱼的遗传方法来识别对恐惧调节至关重要的神经元群。首先，我们进行了大规模的基因捕获和增强子捕获筛选，并创建了在大脑特定区域表达 Gal4FF（Gal4 转录激活剂的工程版本）的转基因鱼品系。然后，我们将这些表达 Gal4FF 的鱼与在 Gal4 结合序列 UAS 下游携带肉毒杆菌神经毒素基因的效应系杂交，并分析双转基因鱼的主动回避恐惧条件反射。我们鉴定了 16 个在不同脑区表达 Gal4FF 的转基因株系，它们表现出回避反应的表现下降。其中两个在位于 Dm 亚区域的神经元群中表达 Gal4，我们将其命名为 120A-Dm 神经元。 120A-Dm 神经元的抑制也会导致巴甫洛夫恐惧条件反射的表现下降。 120A-Dm 神经元大部分是谷氨酸能神经元，并且投射到其他大脑区域，包括下丘脑和腹侧端脑。在此，我们鉴定了斑马鱼 Dm 中对于恐惧调节至关重要的神经元亚群。我们认为这些神经元的功能相当于哺乳动物大脑皮层杏仁核中的神经元，介导条件刺激与非条件刺激的关联。因此，该研究为理解脊椎动物介导恐惧调节的功能神经回路的进化保守性和多样化奠定了基础。本文的在线版本 (10.1186/s12915-018-0502-y) 包含补充材料，可供授权用户使用。
Fear conditioning is a form of learning essential for animal survival and used as a behavioral paradigm to study the mechanisms of learning and memory. In mammals, the amygdala plays a crucial role in fear conditioning. In teleost, the medial zone of the dorsal telencephalon (Dm) has been postulated to be a homolog of the mammalian amygdala by anatomical and ablation studies, showing a role in conditioned avoidance response. However, the neuronal populations required for a conditioned avoidance response via the Dm have not been functionally or genetically defined. We aimed to identify the neuronal population essential for fear conditioning through a genetic approach in zebrafish. First, we performed large-scale gene trap and enhancer trap screens, and created transgenic fish lines that expressed Gal4FF, an engineered version of the Gal4 transcription activator, in specific regions in the brain. We then crossed these Gal4FF-expressing fish with the effector line carrying the botulinum neurotoxin gene downstream of the Gal4 binding sequence UAS, and analyzed the double transgenic fish for active avoidance fear conditioning. We identified 16 transgenic lines with Gal4FF expression in various brain areas showing reduced performance in avoidance responses. Two of them had Gal4 expression in populations of neurons located in subregions of the Dm, which we named 120A-Dm neurons. Inhibition of the 120A-Dm neurons also caused reduced performance in Pavlovian fear conditioning. The 120A-Dm neurons were mostly glutamatergic and had projections to other brain regions, including the hypothalamus and ventral telencephalon. Herein, we identified a subpopulation of neurons in the zebrafish Dm essential for fear conditioning. We propose that these are functional equivalents of neurons in the mammalian pallial amygdala, mediating the conditioned stimulus–unconditioned stimulus association. Thus, the study establishes a basis for understanding the evolutionary conservation and diversification of functional neural circuits mediating fear conditioning in vertebrates. The online version of this article (10.1186/s12915-018-0502-y) contains supplementary material, which is available to authorized users.
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影响因子：
56.9
作者：
Eisenberg, M;Kobilo, T;Dudai, Y
通讯作者：
Dudai, Y
DOI：
10.1073/pnas.0900470106
发表时间：
2009-06-16
影响因子：
11.1
作者：
Koide, Tetsuya;Miyasaka, Nobuhiko;Yoshihara, Yoshihiro
通讯作者：
Yoshihara, Yoshihiro
影响因子：
2.5
作者：
Brox, A;Puelles, L;Medina, L
通讯作者：
Medina, L
影响因子：
--
作者：
Kawakami K;Abe G;Asada T;Asakawa K;Fukuda R;Ito A;Lal P;Mouri N;Muto A;Suster ML;Takakubo H;Urasaki A;Wada H;Yoshida M
通讯作者：
Yoshida M
影响因子：
4.8
作者：
Asakawa, Kazuhide;Kawakami, Koichi
通讯作者：
Kawakami, Koichi