Towards mouse models of perseveration: a heritable component in extinction of operant behavior in fourteen standard and recombinant inbred mouse lines

Extinction of instrumental responses is an essential skill for adaptive behavior such as foraging. So far, only few studies have focused on extinction following appetitive conditioning in mice. We studied extinction of appetitive operant lever-press behavior in six standard inbred mouse strains (A/J, C3H/HeJ, C57BL/6J, DBA/2J, BALB/cByJ and NOD/Ltj) and eight recombinant inbred mouse lines. From the response rates at the end of operant and extinction training we computed an extinction index, with higher values indicating better capability to omit behavioral responding in absence of reward. This index varied highly across the mouse lines tested, and the variability was partially due to a significant heritable component of 12.6%.To further characterize the relationship between operant learning and extinction, we calculated the slope of the time course of extinction across sessions. While many strains showed a considerable capacity to omit responding when lever pressing was no longer rewarded, we found a few lines showing an abnormally high perseveration in lever press behavior, showing no decay in response scores over extinction sessions.No correlation was found between operant and extinction response scores, suggesting that appetitive operant learning and extinction learning are dissociable, a finding in line with previous studies indicating that these forms of learning are dependent on different brain areas. These data shed light on the heritable basis of extinction learning and may help develop animal models of addictive habits and other perseverative disorders, such as compulsive food seeking and eating.     

Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms

Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction. It scrutinised the stability and robustness of the phenotype of enhanced Pavlovian conditioning reported in mice with forebrain neuronal deletion of glycine transporter 1 by evaluating the possible presence of sex and circadian dependency, and its consistency across aversive and appetitive conditioning paradigms. The Pavlovian phenotype was essentially unaffected by the time of testing between the two circadian phases, but it was modified by sex in both conditioning paradigms. We observed that the effect size of the phenotype was strongest in female mice tested during the dark phase in the aversive paradigm. Critically, the presence of the phenotype in female mutants was accompanied by an increase in resistance to extinction. Similarly, enhanced conditioned responding once again emerged solely in female mutants in the appetitive conditioning experiment, which was again associated with an increased resistance to extinction across days, but male mutants exhibited an opposite trend towards facilitation of extinction. The present study has thus added hitherto unknown qualifications and specifications of a previously reported memory enhancing phenotype in this mouse line by identifying the determinants of the magnitude and direction of the expressed phenotype. This in-depth comparative approach is of value to the interpretation of behavioural findings in general.     

Predicting Election Outcomes from Positive and Negative Trait Assessments of Candidate Images

Conventional wisdom, and a growing body of behavioral research, suggests that the nonverbal image of a candidate influences voter decision making. We presented subjects with images of political candidates and asked them to make four trait judgments based solely on viewing the photographs. Subjects were asked which of the two faces exhibited more competence, attractiveness, deceitfulness, and threat, which are arguably four of the most salient attributes that can be conveyed by faces. When we compared our subjects' choices to the actual election outcomes, we found that the candidates chosen as more likely to physically threaten the subjects actually lost 65% of the real elections. As expected, our findings support the conclusions of Todorov, Mandisodza, Goren, and Hall (2005 ) by showing a positive correlation between the competence judgments and the real election outcomes. Surprisingly, attractiveness was correlated with losing elections, with the effect being driven by faces of candidates who looked politically incompetent yet personally attractive. Our findings have implications for future research on negative political communication, as they suggest that both threatening first impressions and fleeting impressions of attractiveness can harm a candidate's electoral chances.     

Impaired emotion recognition in music in Parkinson’s disease

Music has the potential to evoke strong emotions and plays a significant role in the lives of many people. Music might therefore be an ideal medium to assess emotion recognition. We investigated emotion recognition in music in 20 patients with idiopathic Parkinson’s disease (PD) and 20 matched healthy volunteers. The role of cognitive dysfunction and other disease characteristics in emotion recognition was also evaluated.     

时间距离、自我差异的自动激活与价值偏好

本研究对时间距离对自我差异的自动激活假说进行了检验。研究首先启动个体不同的时间自我知觉,然后利用评价性条件反射使先前激活的自我知觉中止,以检验对价值偏好的影响。结果证实了本研究的假设,当消极情绪词语和自我词语同时启动时,先前激活的自我知觉回落到未激活前的基线水平,并使得远期时间距离所引发的可能自我差异或近期时间距离所引发的当前自我差异减弱,从而导致价值偏好不再随时间线索发生系统改变。研究最后讨论了这一发现对自我调节研究的意义。     

长期双酚A暴露对成年小鼠恐惧记忆的影响

双酚A (bisphenol, BPA)是一种广泛应用于塑料制品的环境内分泌干扰物, 具有弱雌激素和抗雄激素活性, 与雌激素受体有一定的亲和力。本实验探讨长期BPA暴露对成年小鼠恐惧记忆的影响及其神经机制。将9周龄雄性小鼠暴露于BPA (0.4、4、40 mg/kg/d) 90 d, 建立小鼠亚慢性BPA暴露模型后, 进行场景性条件恐惧训练, 然后分别在电击后1 hr及24 hr检测小鼠的僵立时间, 同时在电击前、电击后1 hr及24 hr检测海马相关蛋白表达变化。结果表明, BPA (4、40 mg/kg/d)暴露延长小鼠场景性条件恐惧训练后1 hr及24 hr的僵立时间。Western blot蛋白检测结果显示, 行为训练前, BPA降低了小鼠NMDA受体NR1亚基表达水平, 上调组蛋白去乙酰化酶2表达。行为训练后1 hr及24 hr, BPA促进海马NMDA受体亚基NR1和组蛋白H3乙酰化表达, 抑制组蛋白去乙酰化酶2表达, 同时促进ERK1/2磷酸化水平。以上结果表明, 长期BPA暴露提高成年小鼠恐惧记忆获得的同时延长恐惧记忆的保持; 该作用可能通过激活海马的ERK1/2通路而改变核内组蛋白乙酰化和NMDA受体水平进行。     

基于知觉的恐惧泛化的认知神经机制

恐惧泛化是条件性恐惧反应转移到另一个相似但安全的刺激的现象。适当的恐惧泛化对人类有积极意义, 而过度的恐惧泛化则不利于个体有效地适应环境。基于知觉的恐惧泛化研究揭示了恐惧泛化的规律, 因而被广泛应用。本文首先梳理了对知觉恐惧泛化的相关研究, 介绍恐惧泛化的经典理论基础—巴普洛夫条件反射以及恐惧泛化梯度; 其次简要回顾基于多个感觉通道(即视觉、听觉、情景)的知觉恐惧泛化研究现状; 再次, 分别对海马、杏仁核、脑岛和前额叶等脑区在恐惧泛化中的作用进行回顾, 进一步总结出恐惧泛化的神经环路结构模型。最后, 简要区分了基于知觉的恐惧泛化和正在兴起的基于概念的恐惧泛化, 进而指出未来研究需要结合基于概念的恐惧泛化、区分被试对刺激的辨别力、增加恐惧刺激材料的准确性及多样化、结合激素等个体差异和多模态脑成像数据来展开。     

Pointing with the eyes: the role of gaze in communicating danger

Facial expression and direction of gaze are two important sources of social information, and what message each conveys may ultimately depend on how the respective information interacts in the eye of the perceiver. Direct gaze signals an interaction with the observer but averted gaze amounts to "pointing with the eyes", and in combination with a fearful facial expression may signal the presence of environmental danger. We used fMRI to examine how gaze direction influences brain processing of facial expression of fear. The combination of fearful faces and averted gazes activated areas related to gaze shifting (STS, IPS) and fear-processing (amygdala, hypothalamus, pallidum). Additional modulation of activation was observed in motion detection areas, in premotor areas and in the somatosensory cortex, bilaterally. Our results indicate that the direction of gaze prompts a process whereby the brain combines the meaning of the facial expression with the information provided by gaze direction, and in the process computes the behavioral implications for the observer.     

Negative self-focused cognitions mediate the effect of trait social anxiety on state anxiety

The cognitive model of social anxiety predicts that negative self-focused cognitions increase anxiety when anticipating social threat. To test this prediction, 36 individuals were asked to anticipate and perform a public-speaking task. During anticipation, negative self-focused cognitions or relaxation were experimentally induced while self-reported anxiety, autonomic arousal (heart rate, heart rate variability, skin conductance level), and acoustic eye-blink startle response were assessed. As predicted, negative self-focused cognitions mediated the effects of trait social anxiety on self-reported anxiety and heart rate variability during negative anticipation. Furthermore, trait social anxiety predicted increased startle amplitudes. These findings support a central assumption of the cognitive model of social anxiety.