The amygdala modulates prefrontal cortex activity relative to conditioned fear

Animals learn that a tone can predict the occurrence of an electric shock through classical conditioning. Mice or rats trained in this manner display fear responses, such as freezing behaviour, when they hear the conditioned tone. Studies using amygdalectomized rats have shown that the amygdala is required for both the acquisition and expression of learned fear responses. Freezing to a conditioned tone is enhanced following damage to the dorsal part of the medial prefrontal cortex, indicating that this area may be involved in fear reduction. Here we show that prefrontal neurons reduce their spontaneous activity in the presence of a conditioned aversive tone as a function of the degree of fear. The depression in prefrontal spontaneous activity is related to amygdala activity but not to the freezing response itself. These data indicate that, in the presence of threatening stimuli, the amygdala controls both fear expression and prefrontal neuronal activity. They suggest that abnormal amygdala-induced modulation of prefrontal neuronal activity may be involved in the pathophysiology of certain forms of anxiety disorder.     

Lesions of the human amygdala impair enhanced perception of emotionally salient events

Commensurate with the importance of rapidly and efficiently evaluating motivationally significant stimuli, humans are probably endowed with distinct faculties and maintain specialized neural structures to enhance their detection. Here we consider that a critical function of the human amygdala is to enhance the perception of stimuli that have emotional significance. Under conditions of limited attention for normal perceptual awareness-that is, the attentional blink-we show that healthy observers demonstrate robust benefits for the perception of verbal stimuli of aversive content compared with stimuli of neutral content. In contrast, a patient with bilateral amygdala damage has no enhanced perception for such aversive stimulus events. Examination of patients with either left or right amygdala resections shows that the enhanced perception of aversive words depends specifically on the left amygdala. All patients comprehend normally the affective meaning of the stimulus events, despite the lack of evidence for enhanced perceptual encoding of these events in patients with left amygdala lesions. Our results reveal a neural substrate for affective influences on perception, indicating that similar neural mechanisms may underlie the affective modulation of both recollective and perceptual experience.     

大鼠杏仁核在条件性恐惧视觉建立过程中的集群编码研究

研究了大鼠在条件性恐惧视觉建立过程中杏仁核对恐惧视觉信息的编码。首先,设计两种不同拓扑结构("十"和"O")图形,利用巴普洛夫条件反射原理建立大鼠条件性恐惧视觉联结,采用多通道神经信号采集系统采集恐惧视觉建立过程中的杏仁核神经元集群响应信号。然后,对神经元响应信号进行有效响应区间的自适应选取,分别采用神经元集群发放频率和集群熵研究条件性恐惧视觉建立的不同阶段杏仁核的集群编码,发现神经元集群在条件性恐惧建立后发放率、熵均有显著增加。最后,采用支持向量机构建条件性恐惧建立过程中不同恐惧水平的分类模型,验证两种编码的效果。结果表明集群熵编码包含更多的非线性信息和时空整合信息,能更有效地实现恐惧视觉建立过程中视觉信息的"恐惧"水平的表征,由此推测大鼠杏仁核神经核团是以集群的方式对恐惧信息进行编码的。     

The endogenous cannabinoid system controls extinction of aversive memories

Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction, its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1) and endocannabinoids are present in memory-related brain areas and modulate memory. Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex, a region known to control extinction of aversive memories. In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala.     

Temporal difference models describe higher-order learning in humans

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.     

Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala

Receptors for N-methyl-D-aspartate (NMDA) seem to have a critical role in synaptic plasticity. NMDA antagonists (such as AP5) prevent induction of long-term potentiation, an activity-dependent enhancement of synaptic efficacy mediated by neural mechanisms that might also underlie learning and memory. They also attenuate memory formation in several behavioural tasks; there are few data, however, implicating an NMDA-sensitive measure of conditioning based on local infusion of antagonists into a brain area tightly coupled to the behavioural response used to assess conditioning. We now show that NMDA antagonists infused into the amygdala block the acquisition, but not the expression, of fear conditioning measured with a behavioural assay mediated by a defined neural circuit (fear-potentiation of the acoustic startle reflex). This effect showed anatomical and pharmacological specificity, and was not attributable to reduced salience of the stimuli of light or shock used in training. The data indicate that an NMDA-dependent process in the amygdala subserves associative fear conditioning.     

Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning

Pavlovian conditioning results when an innocuous stimulus, such as an odour, is paired with a behaviourally relevant stimulus, such as a foot-shock, so that eventually the former stimulus alone will elicit the behavioural response of the latter. The lateral nucleus of the amygdala (LAT) is necessary for the emotional memory formation in this paradigm. Enhanced neuronal firing in LAT to conditioned stimuli emerge in parallel with the behavioural changes and are dependent on local dopamine. To study the changes in neuronal excitability and synaptic drive that contribute to the pavlovian conditioning process, here we used in vivo intracellular recordings to examine LAT neurons during pavlovian conditioning in rats. We found that repeated pairings of an odour with a foot-shock resulted in enhanced post-synaptic potential (PSP) responses to the odour and increased neuronal excitability. However, a non-paired odour displayed PSP decrement. The dopamine antagonist haloperidol blocked the PSP enhancement and associated increased neuronal excitability, without reversing previous conditioning. These results demonstrate that conditioning and habituation processes produce opposite effects on LAT neurons and that dopamine is important in these events, consistent with its role in emotional memory formation.     

The primate amygdala represents the positive and negative value of visual stimuli during learning

Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala.     

Protein synthesis inhibition in the basolateral nucleus of amygdala facilitates extinction of auditory fear memory

It is known that consolidation of fear conditioning requires de novo protein synthesis in the amygdala. However, there is controversy about the role of protein synthesis in post-retrieval extinction of fear memory. The present study investigated the effect of protein synthesis inhibition (PSI) in the baso- lateral nucleus of amygdala (BLA) on post-retrieval extinction of auditory fear memory. Intra-BLA infu- sion of the protein synthesis inhibitor anisomycin ‘0’ h post-retrieval facilitated the extinction, but was ineffective if the memory was not retrieved. Anisomycin had no effect on the extinction when it was infused 6 h post-retrieval. The present results suggest that there exists a protein-synthesis-dependent mechanism in the BLA that retards extinction of auditory fear memory.     

Encoding of conditioned fear in central amygdala inhibitory circuits

The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour.     

杏仁核在疼痛及疼痛引起的情感和认知障碍中的作用

疼痛是一种不愉快的感觉和情绪体验, 伴随有强烈的负性情绪(如厌恶、恐惧、焦虑等)。 杏仁核作为边缘系统的皮质下中枢,在情绪反应中具有重要作用。我们的研究表明杏仁核在疼痛调制,特别是疼痛情绪反应中起关键作用。本文综述了杏仁核在疼痛及疼痛引起的焦虑行为和认知功能障碍中的作用。     

Innate versus learned odour processing in the mouse olfactory bulb

The mammalian olfactory system mediates various responses, including aversive behaviours to spoiled foods and fear responses to predator odours. In the olfactory bulb, each glomerulus represents a single species of odorant receptor. Because a single odorant can interact with several different receptor species, the odour information received in the olfactory epithelium is converted to a topographical map of multiple glomeruli activated in distinct areas in the olfactory bulb. To study how the odour map is interpreted in the brain, we generated mutant mice in which olfactory sensory neurons in a specific area of the olfactory epithelium are ablated by targeted expression of the diphtheria toxin gene. Here we show that, in dorsal-zone-depleted mice, the dorsal domain of the olfactory bulb was devoid of glomerular structures, although second-order neurons were present in the vacant areas. The mutant mice lacked innate responses to aversive odorants, even though they were capable of detecting them and could be conditioned for aversion with the remaining glomeruli. These results indicate that, in mice, aversive information is received in the olfactory bulb by separate sets of glomeruli, those dedicated for innate and those for learned responses.     

刺激大鼠杏仁外侧核对听皮层神经元调频声反应的影响

采用在体细胞外单细胞记录方法,研究电刺激杏仁外侧核对调频声所诱发的听皮层神经元反应的影响.实验在34只乌拉坦麻醉的SD大鼠上进行,在皮层41区记录了113个对调频声有反应的细胞电活动.观察发现,这些神经元对调频声刺激的反应可分为ON反应,OFF反应,ON-OFF反应,持续性反应和给声抑制反应几种类型.在观察对其中42个神经元的声反应时给予了杏仁外侧核电刺激,其中22%的神经元反应被易化,48%的神经元反应受到了抑制,另外30%神经元的声反应未受杏仁外侧核刺激的影响.这些影响进一步表明,杏仁复合体可在皮层水平参与听觉上传信息的处理,包括听觉信息的加工与整合.同时也表明杏仁核在上传听觉信息的筛选中可能具有重要的作用.     

A mechanism for impaired fear recognition after amygdala damage

Ten years ago, we reported that SM, a patient with rare bilateral amygdala damage, showed an intriguing impairment in her ability to recognize fear from facial expressions. Since then, the importance of the amygdala in processing information about facial emotions has been borne out by a number of lesion and functional imaging studies. Yet the mechanism by which amygdala damage compromises fear recognition has not been identified. Returning to patient SM, we now show that her impairment stems from an inability to make normal use of information from the eye region of faces when judging emotions, a defect we trace to a lack of spontaneous fixations on the eyes during free viewing of faces. Although SM fails to look normally at the eye region in all facial expressions, her selective impairment in recognizing fear is explained by the fact that the eyes are the most important feature for identifying this emotion. Notably, SM's recognition of fearful faces became entirely normal when she was instructed explicitly to look at the eyes. This finding provides a mechanism to explain the amygdala's role in fear recognition, and points to new approaches for the possible rehabilitation of patients with defective emotion perception.     

β-Adrenergic activation enhances NMDA-induced current in pyramidal cells of the basolateral nucleus of amygdala

NMDA receptor （NMDA-R） in the amygdala complex is critical for both long-term potentiation （LTP） and formation of conditioned fear memory. It is reported that activation of β-adrenoceptors （β-AR） in the amygdala facilitates LTP and enhances memory consolidation. The present study examined the regulatory effect of β-AR activation on NMDA-R mediated current in pyramidal cells of the basolateral nucleus of amygdala （BLA）, using whole-cell recording technique. Bath application of the β-AR agonist isoproterenol enhanced NMDA-induced current, and this facilitatory effect was blocked by co-administered propranolol, a β-AR antagonist. The facilitatory effect of isoproterenol on NMDA-induced current could not be induced when the protein kinase A （PKA） inhibitor Rp-cAMPs was added in electrode internal solution.The present results suggest that β-AR activation in the BLA could modulate NMDA-R activity directly and positively, probably via PKA.     

Amygdala intercalated neurons are required for expression of fear extinction

Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders. In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala, the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala (BLA), and contribute inhibitory projections to the central nucleus (CEA), the main output station of the amygdala for conditioned fear responses. Thus, after extinction training, ITC cells could reduce the impact of conditioned-stimulus-related BLA inputs to the CEA by means of feed-forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing micro-opioid receptors (microORs). Electron microscopic observations revealed that the incidence of microOR-immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that microORs typically have a post-synaptic location in ITC cells. In keeping with this, bilateral infusions of the microOR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.     

Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval

'New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.     

新型复合空调系统的结露情况及舒适性数值模拟

为了对竖壁贴附射流与地板辐射复合空调系统的结露情况及舒适性进行数值研究,建立室内复合空调模型,以实测数据作为边界条件,利用 Airpak3.0 软件对该系统的热环境进行数值模拟,分析设计相对湿度、送风速度以及排风口位置对室内热环境的影响,定性地分析室内各工况下相对湿度,PMV,PPD的特点,从而为竖壁贴附射流与地板辐射复合系统合理的运行设计提供了参考依据。     

杏仁核参与情绪记忆的脑功能成像研究述评

脑功能成像技术近年来已应用于情绪记忆的研究,相关的研究结果扩展了依据动物实验所得到的有关结论.作者主要对近年来情绪记忆的编码和提取阶段的脑成像研究进行了综述.研究表明,杏仁核在情绪记忆中的作用不仅局限在巩固阶段,它的作用在编码过程的初期已显示出来,并参与记忆的提取过程.脑区相关和联结模型强调了杏仁核与内侧颞叶等之间的交互作用.已有的研究还表明,刺激类型是影响情绪记忆的重要因素之一.杏仁核还参与对情绪的刺激类型、情绪记忆的生动感和主观性的加工.在今后的研究中将多种神经科学的技术相结合会更深入地揭示情绪记忆的脑机制.     

设定参数对空调系统能耗的影响

 选择位于深圳的一栋小面积办公建筑为例,建立了建筑空调系统的物理和数学模型,基于EES 和Matlab 软件计算模拟,研究了空调系统的室内设定温度、送风温差、冷冻水和冷却水温差参数对空调系统能效比(EER)、制冷系数(COP)、输送效率和功耗等指标的影响。结果表明,室内设定温度每升高1℃,空调冷负荷减少5.6%,COP 和EER 分别升高7.2%和4.75%;送风温度每升高1℃,冷负荷下降4%,COP 和EER 分别降低5.2%和4.64%,以设备总功耗为单一指标,送风温差9.5℃为最佳值;冷冻水温差每升高1℃,冷冻水输送系数升高7.85%;冷却水温差每升高1℃,冷却水输送系数升高8.68%。该结果对空调设计和施工具有指导意义。