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化学生物遗传抑制揭示基底杏仁核参与相对而非绝对威胁的加工过程。

Chemogenetic Inhibition Reveals That Processing Relative But Not Absolute Threat Requires Basal Amygdala.

机构信息

Department of Psychology, University of Evansville, Evansville Indiana 47722,

Center for Neural Science, New York University, New York, New York 10003.

出版信息

J Neurosci. 2019 Oct 23;39(43):8510-8516. doi: 10.1523/JNEUROSCI.2530-18.2019. Epub 2019 Sep 6.

Abstract

While our understanding of appetitive motivation has benefited immensely from the use of selective outcome devaluation tools, the same cannot be said about aversive motivation. Findings from appetitive conditioning studies have shown that basal amygdala is required for behaviors that are sensitive to updates in outcome value, but similar results in aversive motivation are difficult to interpret due to a lack of outcome specificity. The studies reported here sought to develop procedures to isolate sensory-specific processes in aversive learning and behavior and to assess the possible contribution of the basal amygdala. Post-training changes to outcome value produced commensurate changes to subsequently tested conditioned responding in male rodents. Specifically, increases in shock intensity (i.e., inflation) augmented, while repeated exposure to (i.e., habituation of) an aversive sound (klaxon-horn) reduced freezing to conditioned stimuli previously paired with these outcomes. This was extended to a discriminative procedure, in which following revaluation of one event, but not the other, responding was found to be dependent on outcome value signaled by each cue. Chemogenetic inactivation of basal amygdala impaired this discrimination between stimuli signaling differently valued outcomes, but did not affect the revaluation process itself. These findings demonstrate a contribution of the basal amygdala to aversive outcome-dependent motivational processes. The specific content of pavlovian associative learning has been well studied in appetitive motivation, where the value of different foods can be easily manipulated. This has facilitated our understanding of the neural circuits that generate different forms of motivation (i.e., sensory specific vs general). Studies of aversive learning have not produced the same degree of understanding with regard to sensory specificity due to a lack of tools for evaluating sensory-specific processes. Here we use a variant of outcome devaluation procedures with aversive stimuli to study the role of basal amygdala in discriminating between aversive stimuli conveying different degrees of threat. These findings have implications for how we study generalized threat to identify dysregulation that can contribute to generalized anxiety.

摘要

虽然我们对欲望动机的理解得益于选择性结果贬值工具的使用,但厌恶动机却并非如此。食欲条件反射研究的结果表明,基底杏仁核对于对结果价值更新敏感的行为是必需的,但由于缺乏结果特异性,厌恶动机的类似结果难以解释。本文报道的研究旨在开发分离厌恶学习和行为中感觉特异性过程的程序,并评估基底杏仁核的可能贡献。训练后改变结果价值会导致雄性啮齿动物随后测试的条件反应发生相应变化。具体来说,增加电击强度(即膨胀)会增强,而反复暴露于(即厌恶声音(警笛喇叭)的习惯化)会减少对先前与这些结果配对的条件刺激的冻结。这扩展到了一个辨别程序,其中在一个事件的重新评估之后,但不是另一个事件的重新评估之后,发现反应取决于每个线索所表示的结果价值。基底杏仁核的化学遗传失活会损害这种对表示不同价值结果的刺激的辨别能力,但不影响重新评估过程本身。这些发现表明基底杏仁核对厌恶的结果依赖性动机过程有贡献。在食欲动机中,已经很好地研究了不同食物的价值可以很容易地操纵的情况下,条件反射联想学习的具体内容。这有助于我们理解产生不同形式动机(即感觉特异性与一般性)的神经回路。由于缺乏评估感觉特异性过程的工具,厌恶学习的研究并没有产生相同程度的理解。在这里,我们使用一种带有厌恶刺激的结果贬值程序的变体来研究基底杏仁核在区分传达不同程度威胁的厌恶刺激方面的作用。这些发现对于我们如何研究广义威胁以确定可能导致广泛性焦虑的失调具有重要意义。

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