From circuits to behavior: Amygdala dysfunction in fragile X syndrome.

IF 2.6 3区医学 Q2 BEHAVIORAL SCIENCES Frontiers in Integrative Neuroscience Pub Date : 2023-01-01 DOI:10.3389/fnint.2023.1128529

Matthew N Svalina, Regina Sullivan, Diego Restrepo, Molly M Huntsman

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Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a repeat expansion mutation in the promotor region of the FMR1 gene resulting in transcriptional silencing and loss of function of fragile X messenger ribonucleoprotein 1 protein (FMRP). FMRP has a well-defined role in the early development of the brain. Thus, loss of the FMRP has well-known consequences for normal cellular and synaptic development leading to a variety of neuropsychiatric disorders including an increased prevalence of amygdala-based disorders. Despite our detailed understanding of the pathophysiology of FXS, the precise cellular and circuit-level underpinnings of amygdala-based disorders is incompletely understood. In this review, we discuss the development of the amygdala, the role of neuromodulation in the critical period plasticity, and recent advances in our understanding of how synaptic and circuit-level changes in the basolateral amygdala contribute to the behavioral manifestations seen in FXS.

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从电路到行为:脆性X综合征的杏仁核功能障碍。

脆性X综合征(Fragile X syndrome, FXS)是一种由脆性X信使核糖核蛋白1 (FMRP)启动子区域重复扩增突变导致的神经发育障碍，导致脆性X信使核糖核蛋白1蛋白(FMRP)转录沉默和功能丧失。FMRP在大脑的早期发育中有着明确的作用。因此，FMRP的缺失对正常的细胞和突触发育造成了众所周知的后果，导致各种神经精神疾病，包括杏仁核基础疾病的患病率增加。尽管我们对FXS的病理生理学有了详细的了解，但对杏仁核基础疾病的精确细胞和电路水平的基础还不完全了解。在这篇综述中，我们讨论了杏仁核的发育，神经调节在关键期可塑性中的作用，以及我们对基底外侧杏仁核突触和回路水平变化如何影响FXS行为表现的理解的最新进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Integrative Neuroscience Neuroscience-Cellular and Molecular Neuroscience

CiteScore

4.60

自引率

2.90%

发文量

148

审稿时长

14 weeks

期刊介绍： Frontiers in Integrative Neuroscience publishes rigorously peer-reviewed research that synthesizes multiple facets of brain structure and function, to better understand how multiple diverse functions are integrated to produce complex behaviors. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Our goal is to publish research related to furthering the understanding of the integrative mechanisms underlying brain functioning across one or more interacting levels of neural organization. In most real life experiences, sensory inputs from several modalities converge and interact in a manner that influences perception and actions generating purposeful and social behaviors. The journal is therefore focused on the primary questions of how multiple sensory, cognitive and emotional processes merge to produce coordinated complex behavior. It is questions such as this that cannot be answered at a single level – an ion channel, a neuron or a synapse – that we wish to focus on. In Frontiers in Integrative Neuroscience we welcome in vitro or in vivo investigations across the molecular, cellular, and systems and behavioral level. Research in any species and at any stage of development and aging that are focused at understanding integration mechanisms underlying emergent properties of the brain and behavior are welcome.