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Frontiers | Haploinsufficiency of the Parkinson’s disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling 前沿 | 帕金森病基因 synaptojanin1 的单倍体缺陷与精神运动兴奋剂和间叶多巴胺信号的异常反应有关
IF 3 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-25 DOI: 10.3389/fnbeh.2024.1359225
Jennifer I. Mejaes, Jacqueline Saenz, Chris O’Brien, Carina M. Pizzano, Ping-Yue Pan, David J. Barker
The synaptojanin-1 (SYNJ1) gene is known to be important for dopamine-related disorders. Recent evidence has demonstrated that Synj1 deficient mice (Synj1+/−) have impairments in dopaminergic synaptic vesicular recycling. However, less is known about how Synj1 deficits affect the mesolimbic system, reward processing, and motivated behavior. To examine the role of the Synj1 gene in motivated behavior, we subjected male and female Synj1+/− and Synj1+/+ mice to a battery of behavioral tests evaluating hedonic responses, effortful responding, and responses to psychomotor stimulants. We observed that Synj1+/− mice exhibit few differences in reward processing and motivated behavior, with normal hedonic responses and motivated responding for sucrose. However, male but not female Synj1+/− demonstrated an attenuated conditioned place preference for cocaine that could not be attributed to deficits in spatial memory. To further understand the dopamine signaling underlying the attenuated response to cocaine in these mutant mice, we recorded nucleus accumbens dopamine in response to cocaine and observed that Synj1+/− male and female mice took longer to reach peak dopamine release following experimenter-administered cocaine. However, female mice also showed slower decay in accumbens dopamine that appear to be linked to differences in cocaine-induced DAT responses. These findings demonstrate that SYNJ1 deficiencies result in abnormal mesolimbic DA signaling which has not previously been demonstrated. Our work also highlights the need to develop targeted therapeutics capable of restoring deficits in DAT function, which may be effective for reversing the pathologies associated with Synj1 mutations.
众所周知,突触素-1(SYNJ1)基因对多巴胺相关疾病非常重要。最近的证据表明,Synj1 基因缺陷小鼠(Synj1+/-)的多巴胺能突触囊泡再循环能力受损。然而,人们对Synj1缺陷如何影响间叶系统、奖赏处理和动机行为还知之甚少。为了研究 Synj1 基因在动机行为中的作用,我们对雌雄 Synj1+/- 和 Synj1+/+ 小鼠进行了一系列行为测试,评估了享乐反应、努力反应和对精神运动兴奋剂的反应。我们观察到,Synj1+/-小鼠在奖赏处理和动机行为方面几乎没有差异,对蔗糖的享乐反应和动机反应正常。然而,雄性而非雌性Synj1+/-小鼠表现出对可卡因的条件性位置偏好减弱,这不能归因于空间记忆的缺陷。为了进一步了解这些突变小鼠对可卡因的反应减弱所依赖的多巴胺信号传导,我们记录了对可卡因反应的伏隔核多巴胺,并观察到 Synj1+/- 雄性和雌性小鼠在实验者给予可卡因后需要更长的时间才能达到多巴胺释放的峰值。然而,雌性小鼠的多巴胺衰减也较慢,这似乎与可卡因诱导的DAT反应的差异有关。这些研究结果表明,SYNJ1缺陷会导致间叶DA信号传导异常,而这是以前从未证实过的。我们的研究还强调了开发能够恢复DAT功能缺陷的靶向治疗药物的必要性,这可能会有效逆转与Synj1突变相关的病理现象。
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引用次数: 0
Editorial: Animal-friendly methods for rodent behavioral testing in neuroscience research. 社论:神经科学研究中啮齿动物行为测试的动物友好型方法。
IF 2.6 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-25 eCollection Date: 2024-01-01 DOI: 10.3389/fnbeh.2024.1431310
Raffaele d'Isa, Stefania Fasano, Riccardo Brambilla
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引用次数: 0
Retrosplenial cortex and aversive conditioning 后脾皮质和厌恶性条件反射
IF 3 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-25 DOI: 10.3389/fnbeh.2024.1341705
Han Yin Cheng, Danielle I. Fournier, Travis P. Todd
The retrosplenial cortex (RSC) is well-known for its contribution to episodic memory, as well as contextual and spatial learning and memory. However, two literatures have also emerged examining the role of the RSC in aversive conditioning. The purpose of this manuscript is to review, and attempt to integrate, these two literatures. We focus on studies in which discrete cues, such as tones, predict the occurrence of aversive outcomes, such as mild shocks. Using both electrophysiological recordings and lesion methods, the first literature has examined RSC contributions to discriminative avoidance conditioning. The second, and more recent literature, has focused on the role of the RSC in Pavlovian fear conditioning. We discuss both literatures in terms of the type of information processed by the RSC, the role of the RSC in memory storage, and how the aversive conditioning literature might be consistent with a role for the RSC in contextual learning and memory.
回脾皮层(RSC)因其对历时记忆以及情境和空间学习与记忆的贡献而闻名。然而,也出现了两种研究 RSC 在厌恶性条件反射中的作用的文献。本手稿旨在回顾并尝试整合这两篇文献。我们将重点放在离散线索(如音调)预测厌恶结果(如轻微电击)发生的研究上。第一篇文献利用电生理记录和病变方法研究了RSC对辨别性回避条件反射的贡献。第二篇文献,也是最近的一篇文献,侧重于研究 RSC 在巴甫洛夫恐惧条件反射中的作用。我们将从RSC处理的信息类型、RSC在记忆存储中的作用以及厌恶性条件反射文献如何与RSC在情境学习和记忆中的作用相一致等方面讨论这两篇文献。
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引用次数: 0
Frontiers | Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons 前沿 | 压力诱导的小鼠焦虑相关行为是由腹侧被盖区 GABA 神经元兴奋性增强驱动的
IF 3 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-24 DOI: 10.3389/fnbeh.2024.1425607
Eric H. Mitten, Anna Souders, Ezequiel Marron Fernandez de Velasco, Kevin Wickman
IntroductionStress and trauma are significant risk factors for many neuropsychiatric disorders and diseases, including anxiety disorders. Stress-induced anxiety symptoms have been attributed to enhanced excitability in circuits controlling fear, anxiety, and aversion. A growing body of evidence has implicated GABAergic neurons of the ventral tegmental area (VTA) in aversion processing and affective behavior.MethodsWe used an unpredictable footshock (uFS) model, together with electrophysiological and behavioral approaches, to investigate the role of VTA GABA neurons in anxiety-related behavior in mice.ResultsOne day after a single uFS session, C57BL/6J mice exhibited elevated anxiety-related behavior and VTA GABA neuron excitability. The enhanced excitability of VTA GABA neurons was correlated with increased glutamatergic input and a reduction in postsynaptic signaling mediated via GABAA and GABAB receptors. Chemogenetic activation of VTA GABA neurons was sufficient to increase anxiety-related behavior in stress-naïve mice. In addition, chemogenetic inhibition of VTA GABA neurons suppressed anxiety-related behavior in mice exposed to uFS.DiscussionThese data show that VTA GABA neurons are an early substrate for stress-induced anxiety-related behavior in mice and suggest that approaches mitigating enhanced excitability of VTA GABA neurons may hold promise for the treatment of anxiety provoked by stress and trauma.
导言压力和创伤是包括焦虑症在内的许多神经精神障碍和疾病的重要风险因素。压力诱发焦虑症状的原因是控制恐惧、焦虑和厌恶的回路兴奋性增强。越来越多的证据表明,腹侧被盖区(VTA)的GABA能神经元与厌恶处理和情感行为有关。方法我们使用不可预知的足震(uFS)模型,结合电生理学和行为学方法,研究了VTA GABA神经元在小鼠焦虑相关行为中的作用。VTA GABA神经元兴奋性的增强与谷氨酸能输入的增加以及通过GABAA和GABAB受体介导的突触后信号传导的减少有关。对VTA GABA神经元的化学激活足以增加应激免疫小鼠的焦虑相关行为。这些数据表明,VTA GABA神经元是应激诱导的小鼠焦虑相关行为的早期底物,并表明缓解VTA GABA神经元兴奋性增强的方法可能有望治疗应激和创伤引发的焦虑。
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引用次数: 0
Frontiers | Dissecting the contribution of human chromosome 21 syntenic regions to recognition memory processes in adult and aged mouse models of Down syndrome 前沿 | 剖析人类 21 号染色体同源区对成年和老年唐氏综合征小鼠模型识别记忆过程的贡献
IF 3 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-24 DOI: 10.3389/fnbeh.2024.1428146
Tara Canonica, Emma J. Kidd, Dorota Gibbins, Eva Lana-Elola, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Mark Good
BackgroundTrisomy of human chromosome 21 (Hsa21) results in a constellation of features known as Down syndrome (DS), the most common genetic form of intellectual disability. Hsa21 is orthologous to three regions in the mouse genome on mouse chromosome 16 (Mmu16), Mmu17 and Mmu10. We investigated genotype-phenotype relationships by assessing the contribution of these three regions to memory function and age-dependent cognitive decline, using three mouse models of DS, Dp1Tyb, Dp(17)3Yey, Dp(10)2Yey, that carry an extra copy of the Hsa21-orthologues on Mmu16, Mmu17 and Mmu10, respectively.HypothesisPrior research on cognitive function in DS mouse models has largely focused on models with an extra copy of the Mmu16 region and relatively little is known about the effects of increased copy number on Mmu17 and Mmu10 on cognition and how this interacts with the effects of aging. As aging is is a critical contributor to cognitive and psychiatric changes in DS, we hypothesised that ageing would differentially impact memory function in Dp1Tyb, Dp(17)3Yey, and Dp(10)2Yey, models of DS.MethodsYoung (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques.ResultsYoung (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques.ConclusionOur results show that distinct Hsa21-orthologous regions contribute differentially to cognitive dysfunction in DS mouse models and that aging interacts with triplication of Hsa21-orthologous genes on Mmu10.
背景人类 21 号染色体(Hsa21)三体综合征(DS)是最常见的遗传性智力残疾。Hsa21与小鼠基因组中的三个区域正交,分别位于小鼠第16号染色体(Mmu16)、Mmu17和Mmu10上。我们使用三种小鼠 DS 模型(Dp1Tyb、Dp(17)3Yey 和 Dp(10)2Yey)研究了基因型与表型之间的关系,通过评估这三个区域对记忆功能和年龄依赖性认知衰退的贡献,这三种模型分别携带 Mmu16、Mmu17 和 Mmu10 上 Hsa21 同源物的额外拷贝。假说先前对 DS 小鼠模型认知功能的研究主要集中在带有 Mmu16 区域额外拷贝的模型上,而对于 Mmu17 和 Mmu10 拷贝数增加对认知的影响以及这种影响与衰老的影响之间的相互作用则知之甚少。由于衰老是导致DS认知和精神变化的关键因素,我们假设衰老会对Dp1Tyb、Dp(17)3Yey和Dp(10)2Yey等DS模型的记忆功能产生不同的影响。方法对幼年(12-13 个月)和老年(18-20 个月)的 Dp1Tyb、Dp(17)3Yey 和 Dp(10)2Yey 小鼠进行了一系列物体识别记忆测试,以评估物体新奇性检测、新位置检测和关联性物体在位记忆。在行为测试之后,使用标准免疫印迹技术分析了海马和额叶皮层组织中谷氨酸能受体蛋白的表达情况。结果年轻(12-13 个月和年老(18-20 个月的 Dp1Tyb、Dp(17)3Yey 和 Dp(10)2Yey 小鼠)小鼠接受了一系列物体识别记忆测试,这些测试评估了物体新奇度检测、新位置检测和联想物体到位记忆。结论我们的研究结果表明,不同的 Hsa21 同源区域对 DS 小鼠模型的认知功能障碍有不同的贡献,而且衰老与 Mmu10 上的 Hsa21 同源基因的三倍化相互影响。
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引用次数: 0
Italian validation of the body odor disgust scale 意大利体味厌恶量表的验证
IF 3 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-06-21 DOI: 10.3389/fnbeh.2024.1389905
Marco Tullio Liuzza, Marta Z. Zakrzewska, Jonas K. Olofsson
IntroductionDisgust sensitivity to body odors plays a role in a set of psychological mechanisms supposedly evolved to avoid pathogens. To assess individual differences in body odor disgust, we previously developed the body odor disgust scale (BODS) and validated it in English. The BODS presents six scenarios where disgust could be evoked by smells coming from an internal source and an external source. The present study aimed to validate the BODS in the Italian population and to find further evidence for its structural, construct, and criterion validity.MethodsWe used two large samples (N = 1,050, F = 527; and N = 402, F = 203, respectively) that were representative of the Italian population for sex and age.ResultsAcross these two studies, we confirmed the hypothesized bifactor structure, with all the items loading onto a general body odor disgust sensitivity factor, and on two specific factors related to the internal structure. In terms of construct validity, we found that the BODS converged with pathogen disgust sensitivity of the three-domain disgust scale (TDDS) but was distinct from a general propensity to experience negative emotions. The BODS showed criterion validity in predicting the behavioral intentions toward COVID-19 avoidance behavior, although it did not seem to be incrementally valid when compared to the TDDS pathogen subscale. We also established scalar measurement invariance of the BODS regarding gender and found that women display higher levels of BODS.DiscussionResults from the Italian version of the BODS indicate its structural, construct, nomological and criterion validity. Furthermore, our result on sex differences in disgust sensitivity are consistent with previous literature, and we discuss them in the broader context of cross-cultural and primate findings that points toward a possible evolutionary explanation of this difference.
导言:对体味的厌恶敏感性在一系列心理机制中发挥着作用,据说这些机制是为了避免病原体而进化而来的。为了评估体味厌恶的个体差异,我们之前开发了体味厌恶量表(BODS),并用英语进行了验证。体味厌恶量表提供了六种情景,分别由来自内部和外部的气味引起厌恶。本研究的目的是在意大利人口中验证 BODS,并为其结构、构造和标准效度寻找进一步的证据。方法我们使用了两个大型样本(分别为 N = 1,050, F = 527;N = 402, F = 203),这两个样本在性别和年龄上都代表了意大利人口。结果在这两项研究中,我们证实了假设的双因子结构,所有项目都加载在一个一般体味厌恶敏感因子上,以及两个与内部结构相关的特定因子上。在建构效度方面,我们发现体味厌恶敏感度与三域厌恶量表(TDDS)中的病原体厌恶敏感度一致,但又有别于一般的负面情绪倾向。在预测 COVID-19 规避行为的行为意向方面,BODS 显示出了标准效度,尽管与 TDDS 病原体分量表相比,BODS 似乎不具有增量效度。我们还确定了 BODS 在性别方面的标度测量不变性,并发现女性的 BODS 水平更高。此外,我们关于厌恶敏感度性别差异的研究结果与之前的文献一致,我们在跨文化和灵长类动物研究结果的大背景下讨论了这些结果,这些研究结果指出了这种差异可能的进化解释。
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引用次数: 0
Erratum: Editorial: Towards a new 3Rs era in experimental research. 勘误:社论:迈向实验研究的 3R 新时代。
IF 3 3区 医学 Q2 Psychology Pub Date : 2024-06-04 eCollection Date: 2024-01-01 DOI: 10.3389/fnbeh.2024.1434372

[This corrects the article DOI: 10.3389/fnbeh.2024.1404294.].

[This corrects the article DOI: 10.3389/fnbeh.2024.1404294.].
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引用次数: 0
Awakenings in triplicate: in ontogeny, after immobility, and to the presence of a congener. Comments on Ilan Golani’s concept of the mobility gradient 一式三份的唤醒:在本体发育过程中,在不动之后,以及在同源物存在的情况下。对伊兰-戈兰尼的流动梯度概念的评论
IF 3 3区 医学 Q2 Psychology Pub Date : 2024-05-30 DOI: 10.3389/fnbeh.2024.1325481
Koenraad Kortmulder
Golani’s concept of the “mobility gradient” describes the unfolding of motor behavior after immobility and in ontogeny. The two processes run parallel and are similar across vertebrates. In both time scales, the trend is for the behavior to progressively become enriched, cover more dimensions (motor expansion) and become less dependent on external stimuli (stimulus-bound). This paper addresses the question whether the gradient extends into social, interactive behavior. Observation of natural groups larger than dyads may help answering that question. As an example, the natural social behavior of a fish, Pethia nigrofasciata is described in some detail. It is concluded that their motor behavior expands in the course of their daily spawning period.
戈兰尼的 "运动梯度 "概念描述了运动行为在不动后和本体发育过程中的展开过程。这两个过程是平行的,在脊椎动物中也是相似的。在这两个时间尺度上,行为的趋势都是逐渐变得丰富,覆盖更多的维度(运动扩展),并减少对外部刺激的依赖(刺激约束)。本文探讨的问题是,这种梯度是否会延伸到社会互动行为中。对大于二人组的自然群体的观察可能有助于回答这个问题。举例来说,本文详细描述了一种鱼--Pethia nigrofasciata 的自然社会行为。结论是,它们的运动行为会在每天的产卵期扩大。
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引用次数: 0
Not seeing the forest for the trees: combination of path integration and landmark cues in human virtual navigation 只见树木不见森林:人类虚拟导航中的路径整合与地标线索相结合
IF 3 3区 医学 Q2 Psychology Pub Date : 2024-05-21 DOI: 10.3389/fnbeh.2024.1399716
Jonas Scherer, Martin M. Müller, Patrick Unterbrink, Sina Meier, Martin Egelhaaf, Olivier J. N. Bertrand, Norbert Boeddeker
IntroductionIn order to successfully move from place to place, our brain often combines sensory inputs from various sources by dynamically weighting spatial cues according to their reliability and relevance for a given task. Two of the most important cues in navigation are the spatial arrangement of landmarks in the environment, and the continuous path integration of travelled distances and changes in direction. Several studies have shown that Bayesian integration of cues provides a good explanation for navigation in environments dominated by small numbers of easily identifiable landmarks. However, it remains largely unclear how cues are combined in more complex environments.MethodsTo investigate how humans process and combine landmarks and path integration in complex environments, we conducted a series of triangle completion experiments in virtual reality, in which we varied the number of landmarks from an open steppe to a dense forest, thus going beyond the spatially simple environments that have been studied in the past. We analysed spatial behaviour at both the population and individual level with linear regression models and developed a computational model, based on maximum likelihood estimation (MLE), to infer the underlying combination of cues.ResultsOverall homing performance was optimal in an environment containing three landmarks arranged around the goal location. With more than three landmarks, individual differences between participants in the use of cues are striking. For some, the addition of landmarks does not worsen their performance, whereas for others it seems to impair their use of landmark information.DiscussionIt appears that navigation success in complex environments depends on the ability to identify the correct clearing around the goal location, suggesting that some participants may not be able to see the forest for the trees.
导言为了成功地从一个地方移动到另一个地方,我们的大脑通常会根据空间线索的可靠性和与特定任务的相关性对其进行动态加权,从而将来自不同来源的感觉输入结合起来。导航中最重要的两个线索是环境中地标性建筑的空间排列,以及行进距离和方向变化的连续路径整合。多项研究表明,在以少量易识别地标为主的环境中,线索的贝叶斯整合为导航提供了很好的解释。为了研究人类在复杂环境中如何处理和组合地标以及路径整合,我们在虚拟现实中进行了一系列三角形补全实验,在这些实验中,我们改变了地标的数量,从开阔的草原到茂密的森林,从而超越了过去研究的空间简单环境。我们用线性回归模型分析了群体和个体的空间行为,并开发了一个基于最大似然估计(MLE)的计算模型,以推断线索的基本组合。在有三个以上地标的情况下,参与者在使用线索方面的个体差异非常明显。讨论似乎在复杂环境中导航的成功与否取决于识别目标位置周围正确空地的能力,这表明有些参与者可能无法做到 "只见树木,不见森林"。
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引用次数: 0
Erratum: Role of environmental enrichment on social interaction, anxiety, locomotion, and memory in Wistar rats under chronic methylphenidate intake 勘误:环境强化对长期摄入哌醋甲酯的 Wistar 大鼠的社会互动、焦虑、运动和记忆的作用
IF 3 3区 医学 Q2 Psychology Pub Date : 2024-05-20 DOI: 10.3389/fnbeh.2024.1431914
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引用次数: 0
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