Left Habenular Activity Attenuates Fear Responses in Larval Zebrafish.

Left Habenular Activity Attenuates Fear Responses in Larval Zebrafish.
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左键的活动减弱了幼虫斑马鱼的恐惧反应。

DOI:
10.1016/j.cub.2017.06.017
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发表时间:
2017-07-24
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Halpern ME
Halpern ME
中科院分区:
其他
文献类型:
--
作者:
Duboué ER;Hong E;Eldred KC;Halpern ME

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恐惧反应是一种防御状态,它确保生物体在威胁存在时的生存。对厌恶性暗示的感知会导致行为和生理上的变化,例如冻结和皮质醇升高,然后在逃避威胁时返回到基线状态。引发恐惧行为的神经系统包括杏仁核、海马体和内侧前额叶皮层。然而,除了一些例子之外,我们对促进从厌恶事件中恢复的大脑区域知之甚少。先前的研究表明,背侧缰核在调节斑马鱼的恐惧反应和大胆。我们现在表明,扰动的固有的左右(LR)不对称的背缰-脚间(dHb-IPN)途径在幼虫阶段加快返回的自发活动后,一个意想不到的负刺激,电击。切断缰核向IPN的传出,或仅切断左侧dHb的传出,可抑制休克后的冻结行为。具有对称、右异构化dHb的个体也表现出增加的冻结。相反,具有对称的、左异构化的dHb的幼虫,或者其中仅左dHb-IPN投射被光遗传学激活的幼虫,在休克后迅速恢复游泳。在体内钙成像揭示了一个神经元子集,主要是在左dHb,其激活与恢复游泳。结果表明左dHb-IPN途径在减弱对恐惧的反应中的功能特化。
Fear responses are defensive states that ensure survival of an organism in the presence of a threat. Perception of an aversive cue causes changes in behavior and physiology, such as freezing and elevated cortisol, followed by a return to the baseline state when the threat is evaded. Neural systems that elicit fear behaviors include the amygdala, hippocampus and medial prefrontal cortex. However, aside from a few examples, little is known about brain regions that promote recovery from an aversive event. Previous studies had implicated the dorsal habenular nuclei in regulating fear responses and boldness in zebrafish. We now show that perturbation of the inherent left-right (L-R) asymmetry of the dorsal habenulo-interpeduncular (dHb-IPN) pathway at larval stages expedites the return of locomotor activity following an unexpected negative stimulus, electric shock. Severing habenular efferents to the IPN, or only those from the left dHb, prolongs the freezing behavior that follows shock. Individuals with symmetric, right isomerized dHb also exhibit increased freezing. In contrast, larvae that have symmetric, left-isomerized dHb, or in which just the left dHb-IPN projection is optogenetically activated, rapidly resume swimming post shock. In vivo calcium imaging reveals a neuronal subset, predominantly in the left dHb, whose activation is correlated with resumption of swimming. The results demonstrate functional specialization of the left dHb-IPN pathway in attenuating the response to fear.
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