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.     

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。     

Understanding patterns of attitude change: When implicit measures show change, but explicit measures do not

A common assumption in research on attitudes is that indirect measures assess relatively stable implicit attitudes, whereas traditional self-report measures assess more recently acquired explicit attitudes that coexist with old, presumably stable implicit attitudes. This assumption seems difficult to reconcile with research showing experimentally induced changes on implicit but not explicit measures. The present research tested a process-account of such asymmetrical patterns. Specifically, we argue that implicit measures show experimental effects that do not emerge on explicit measures when (a) the pairing of an attitude object with positive or negative valence creates new automatic associations in memory, and, at the same time, (b) the consideration of additional information about the attitude object eliminates the impact of automatic associations on self-reported evaluative judgments. Results from three studies support these predictions. Implications for research on attitude change are discussed.     

对听感觉运动门控自上而下调节的动物模型和神经机制

对惊反射的前脉冲抑制是减少干扰影响、保护脑内信息加工的重要机制。它既是研究感觉运动门控的模型, 也是探究精神分裂症机制的模型。前脉冲抑制可被选择性注意和情绪等高级认知活动所调节。本论文工作围绕着恐惧条件化和知觉空间分离去掩蔽(空间选择性注意)对听觉前脉冲抑制多层次化的自上而下调节, 在大鼠行为模型、神经通路、神经电生理机制等几个层次上开展了系统性研究, 并引入了精神分裂症的神经发育模型, 证实早期社会隔离饲养对前脉冲抑制注意调节的破坏影响。本论文研究成果不仅对认识正常情况下脑在复杂刺激场景中的信息加工机制有重要意义, 以感觉运动门控认知调节功能缺失为基础的动物模型也将推动精神分裂症心理学和神经生物学机制的研究。     

Second-order conditioning of human causal learning

This article provides the first demonstration of a reliable second-order conditioning (SOC) effect in human causal learning tasks. It demonstrates the human ability to infer relationships between a cause and an effect that were never paired together during training. Experiments 1a and 1b showed a clear and reliable SOC effect, while Experiments 2a and 2b demonstrated that first-order extinction did not affect SOC. These results were similar to those found in animal and human conditioning and suggested that a similar associative mechanism could explain these effects. However, they can also be used to look into the underlying causal mental model people build and store while they are learning this task. From a cognitive view, overall results suggest that an independent rather than a chain causal mental model is stored after second-order learning in human causal tasks.