Team "synapse in cognition", UMR 5297, University of Bordeaux, Bordeaux, France; Team "synapse in cognition", UMR 5297, Centre National de la recherche scientifique, Bordeaux, France.
CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt B):392-397. doi: 10.1016/j.pnpbp.2017.07.028. Epub 2017 Aug 1.
The amygdala is a part of the limbic circuit that has been extensively studied in terms of synaptic connectivity, plasticity and cellular organization since decades (Ehrlich et al., 2009; Ledoux, 2000; Maren, 2001). Amygdala sub-nuclei, including lateral, basolateral and central amygdala appear now as "hubs" providing in parallel and in series neuronal processing enabling the animal to elicit freezing or escaping behavior in response to external threats. In rodents, these behaviors are easily observed and quantified following associative fear conditioning. Thus, studies on amygdala circuit in association with threat/fear behavior became very popular in laboratories and are often used among other behavioral tests to evaluate learning abilities of mouse models for various neuropsychiatric conditions including genetically encoded intellectual disabilities (ID). Yet, more than 100 human X-linked genes - and several hundreds of autosomal genes - have been associated with ID in humans. These mutations introduced in mice can generate social deficits, anxiety dysregulations and fear learning impairments (McNaughton et al., 2008; Houbaert et al., 2013; Jayachandran et al., 2014; Zhang et al., 2015). Noteworthy, a significant proportion of the coded ID gene products are synaptic proteins. It is postulated that the loss of function of these proteins could destabilize neuronal circuits by global changes of the balance between inhibitory and excitatory drives onto neurons. However, whereas amygdala related behavioral deficits are commonly observed in ID models, the role of most of these ID-genes in synaptic function and plasticity in the amygdala are only sparsely studied. We will here discuss some of the concepts that emerged from amygdala-targeted studies examining the role of syndromic and non-syndromic ID genes in fear-related behaviors and/or synaptic function. Along describing these cases, we will discuss how synaptic deficits observed in amygdala circuits could impact memory formation and expression of conditioned fear.
杏仁核是边缘回路的一部分，几十年来，人们一直在研究其突触连接、可塑性和细胞组织（Ehrlich 等人，2009 年；Ledoux，2000 年；Maren，2001 年）。杏仁核亚核，包括外侧、基底外侧和中央杏仁核，现在似乎是“枢纽”，提供并行和串行的神经元处理，使动物能够对外部威胁产生冻结或逃避行为。在啮齿动物中，这些行为很容易在关联恐惧条件反射后观察和量化。因此，与威胁/恐惧行为相关的杏仁核回路研究在实验室中变得非常流行，并且经常与其他行为测试一起用于评估各种神经精神疾病模型（包括遗传性智力障碍）的学习能力。然而，在人类中，已有 100 多个 X 连锁基因和几百个常染色体基因与智力障碍相关。这些在小鼠中引入的突变会导致社交缺陷、焦虑失调和恐惧学习障碍（McNaughton 等人，2008 年；Houbaert 等人，2013 年；Jayachandran 等人，2014 年；Zhang 等人，2015 年）。值得注意的是，编码 ID 基因产物的很大一部分是突触蛋白。据推测，这些蛋白质的功能丧失可能会通过神经元上抑制性和兴奋性驱动之间的平衡发生全局变化来破坏神经元回路。然而，尽管 ID 模型中通常观察到与杏仁核相关的行为缺陷，但大多数这些 ID 基因在杏仁核中的突触功能和可塑性中的作用研究甚少。我们将在这里讨论一些从靶向杏仁核的研究中出现的概念，这些研究检查了综合征和非综合征性 ID 基因在与恐惧相关的行为和/或突触功能中的作用。在描述这些情况的同时，我们将讨论在杏仁核回路中观察到的突触缺陷如何影响记忆形成和条件恐惧的表达。
