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暴露于先天和条件性威胁期间腹内侧下丘脑活动的特征

Characterization of ventromedial hypothalamus activity during exposure to innate and conditioned threats.

作者信息

Tobias Brooke C, Schuette Peter J, Maesta-Pereira Sandra, Torossian Anita, Wang Weisheng, Sethi Ekayana, Adhikari Avishek

机构信息

Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Eur J Neurosci. 2023 Apr;57(7):1053-1067. doi: 10.1111/ejn.15937. Epub 2023 Feb 24.

Abstract

In the face of imminent predatory danger, animals quickly detect the threat and mobilize key survival defensive actions, such as escape and freezing. The dorsomedial portion of the ventromedial hypothalamus (VMH) is a central node in innate and conditioned predator-induced defensive behaviours. Prior studies have shown that activity of steroidogenic factor 1 (sf1)-expressing VMH cells is necessary for such defensive behaviours. However, sf1-VMH neural activity during exposure to predatory threats has not been well characterized. Here, we use single-cell recordings of calcium transients from VMH cells in male and female mice. We show this region is activated by threat proximity and that it encodes future occurrence of escape but not freezing. Our data also show that VMH cells encoded proximity of an innate predatory threat but not a fear-conditioned shock grid. Furthermore, chemogenetic activation of the VMH increases avoidance of innate threats, such as open spaces and a live predator. This manipulation also increased freezing towards the predator, without altering defensive behaviours induced by a shock grid. Lastly, we show that optogenetic VMH activation recruited a broad swath of regions, suggestive of widespread changes in neural defensive state. Taken together, these data reveal the neural dynamics of the VMH during predator exposure and further highlight its role as a critical component of the hypothalamic predator defense system.

摘要

面对迫在眉睫的捕食性危险时,动物能迅速察觉到威胁并调动关键的生存防御行为,如逃跑和静止不动。腹内侧下丘脑(VMH)的背内侧部分是先天和条件性捕食者诱导的防御行为的核心节点。先前的研究表明,表达类固醇生成因子1(sf1)的VMH细胞的活动对于此类防御行为是必要的。然而,在暴露于捕食性威胁期间,sf1-VMH神经活动尚未得到很好的表征。在这里,我们对雄性和雌性小鼠VMH细胞的钙瞬变进行单细胞记录。我们发现该区域会因威胁临近而被激活,并且它编码未来逃跑行为的发生,但不编码静止不动行为。我们的数据还表明,VMH细胞编码先天捕食性威胁的临近,但不编码恐惧条件性电击网格。此外,VMH的化学遗传激活增加了对先天威胁(如开放空间和活体捕食者)的回避。这种操作还增加了对捕食者的静止不动行为,而不改变由电击网格诱导的防御行为。最后,我们表明光遗传学激活VMH会募集广泛的脑区,这表明神经防御状态发生了广泛变化。综上所述,这些数据揭示了捕食者暴露期间VMH的神经动力学,并进一步突出了其作为下丘脑捕食者防御系统关键组成部分的作用。

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