Cellular processes in the amygdala: gates to emotional memory?

The amygdala is considered a core structure of the so-called limbic system and has been implicated in a variety of functions, including emotional interpretation of sensory information, emotional arousal, emotional memory, fear and anxiety, and related clinical disorders. Despite the clinical and functional importance of the amygdala, it is only recently that some general principles of intra-amygdaloid mechanisms of signal processing that are relevant for fear behavior and memory have emerged from behavioral, anatomical, electrophysiological, and neurochemical studies performed in the amygdala of various mammalian species in vivo, in situ and in vitro.     

突触细胞黏附分子在应激中作用的研究进展

突触细胞黏附分子是一类介导突触前、后膜结构和功能互作的膜表面糖蛋白,可以动态调节突触活动和可塑性,其表达与功能受到环境因素调控.突触细胞黏附分子亦是应激反应重要的效应分子之一,可介导应激对认知和情绪的不良影响.本文综述近年来突触细胞黏附分子在应激中作用的研究进展,旨在为应激相关障碍的分子机制研究和药物研发提供思路.     

大鼠恐惧应激模型的建立及其视觉认知效果分析

目的构建不同程度恐惧应激大鼠模型,探究恐惧应激对LE大鼠视觉认知能力的影响。方法采用足底电击作为应激刺激,设计认知抉择实验,采集杏仁核脑区神经响应信号进行功能网络分析,评价大鼠视觉认知效果。首先,将实验大鼠分成强(S+)、弱(S)恐惧应激组与对照组(N),分别设定不同强度的足底电击刺激;然后对其进行单一图形"△"的视觉认知强化训练;最后,采用双图("△"和"十"图形)进行视觉抉择测试实验。另外结合复杂网络理论,构建恐惧应激大鼠杏仁核神经核团的视觉认知功能网络,通过平均路径长度和聚类系数表征脑功能网路的信息传递效率。结果完成视觉认知强化训练所需时间,S+组显著高于S、N组,强化训练前期S组显著高于N组,后期两组无显著性差异;认知抉择实验中,S组与N组均形成视觉认知联结,而S+组未形成视觉认知联结;脑功能网络分析中,S组与N组杏仁核神经元之间形成有效的视觉信息传递,而S+组未形成。结论恐惧应激对视觉认知造成消极影响,且随着恐惧程度的增强认知效果显著变差。     

Amygdaloid and non-amygdaloid fear both influence avoidance of risky foraging in hungry rats

Considerable evidence seems to show that emotional and reflex reactions to feared situations are mediated by the amygdala. It might therefore seem plausible to expect that amygdala-coded fear should also influence decisions when animals make choices about instrumental actions. However, there is not good evidence of this. In particular, it appears, though the literature is conflicted, that once learning is complete, the amygdala may often not be involved in instrumental avoidance behaviours. It is therefore of interest that we have found in rats living for extended periods in a semi-naturalistic ‘closed economy’, where they were given random shocks in regions that had to be entered to obtain food, choices about feeding behaviour were in fact influenced by amygdala-coded fear, in spite of the null effect of amygdalar lesions on fear of dangerous location per se. We suggest that avoidance of highly motivated voluntary behaviour does depend in part on fear signals originating in the amygdala. Such signalling may be one role of well-known projections from amygdala to cortico-striate circuitry.     

K‐Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation

Neuronal histone acetylation has been linked to memory consolidation, and targeting histone acetylation has emerged as a promising therapeutic strategy for neuropsychiatric diseases. However, the role of histone‐modifying enzymes in the adult brain is still far from being understood. Here we use RNA sequencing to screen the levels of all known histone acetyltransferases (HATs) in the hippocampal CA1 region and find that K‐acetyltransferase 2a (Kat2a)—a HAT that has not been studied for its role in memory function so far—shows highest expression. Mice that lack Kat2a show impaired hippocampal synaptic plasticity and long‐term memory consolidation. We furthermore show that Kat2a regulates a highly interconnected hippocampal gene expression network linked to neuroactive receptor signaling via a mechanism that involves nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). In conclusion, our data establish Kat2a as a novel and essential regulator of hippocampal memory consolidation.     

Can zebrafish Danio rerio learn about predation risk? The effect of a previous experience on the cortisol response in subsequent encounters with a predator

Experienced zebrafish Danio rerio, when subjected to visual contact with a predator, did not show elevated cortisol levels and had values similar to control fish. The main hypothesis is that experienced D. rerio know about the real relevance of this prey–predator encounter. In summary, the data presented provide evidence that experienced D. rerio does not produce elevated cortisol in response to sighting a possible predator, and might suggest that these fish can learn about dangerous situations.     

A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories

Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17-19-day-old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory.     

Mechanisms of epigenetic memory and addiction

Epigenetic regulation of cellular identity and function is at least partly achieved through changes in covalent modifications on DNA and histones. Much progress has been made in recent years to understand how these covalent modifications affect cell identity and function. Despite the advances, whether and how epigenetic factors contribute to memory formation is still poorly understood. In this review, we discuss recent progress in elucidating epigenetic mechanisms of learning and memory, primarily at the DNA level, and look ahead to discuss their potential implications in reward memory and development of drug addiction.     

The Emotional Brain, Fear, and the Amygdala

1. Considerable progress has been made over the past 20 years in relating specific circuits of the brain to emotional functions. Much of this work has involved studies of Pavlovian or classical fear conditioning, a behavioral procedure that is used to couple meaningless environmental stimuli to emotional (defense) response networks.2. The major conclusion from studies of fear conditioning is that the amygdala plays critical role in linking external stimuli to defense responses.3. Before describing research on the role of the amygdala in fear conditioning, though, it will be helpful to briefly examine the historical events that preceded modern research on conditioned fear.     

条件化恐惧记忆消退的神经振荡机制

恐惧作为个体应对内外界危险因素形成的自我保护机制的一部分,在生物体的生存中发挥着重要作用.但过度的恐惧不仅对个体生存无益,反而易引发创伤后应激障碍、焦虑等精神疾病,严重影响个体生活质量.临床上通常采用基于行为学研究结果的暴露疗法对恐惧相关疾病进行治疗,然而在患者处于治疗环境之外的时候,上述症状经常会复发.因此,解析恐惧记忆相关神经环路内信息处理的神经机制,对于理解这些疾病的发生发展,寻求切实有效的治疗方案至关重要.大量研究表明与恐惧记忆消退相关的脑区主要涉及杏仁核、内侧前额叶和海马.在恐惧消退的过程中,这3个脑区表现出特定的神经振荡模式,而且这些活动也具有同步性,构成了恐惧记忆成功消退的神经基础.未来可利用基于神经神经振荡的无创性脑刺激手段干预恐惧记忆消退的神经环路,以促进恐惧记忆的消退并避免复发,为恐惧相关障碍的临床治疗提供重要的科学依据.