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Local field potentials in dorsal anterior cingulate sulcus reflect rewards but not travel time costs during foraging. 背前扣带沟的局部场电位反映觅食过程中的奖励,但不反映觅食过程中的旅行时间成本。
Pub Date : 2019-01-18 eCollection Date: 2019-01-01 DOI: 10.1177/2398212818817932
Arjun Ramakrishnan, Benjamin Y Hayden, Michael L Platt

To maximise long-term reward rates, foragers deciding when to leave a patch must compute a decision variable that reflects both the immediately available reward and the time costs associated with travelling to the next patch. Identifying the mechanisms that mediate this computation is central to understanding how brains implement foraging decisions. We previously showed that firing rates of dorsal anterior cingulate sulcus neurons incorporate both variables. This result does not provide information about whether integration of information reflected in dorsal anterior cingulate sulcus spiking activity arises locally or whether it is inherited from upstream structures. Here, we examined local field potentials gathered simultaneously with our earlier recordings. In the majority of recording sites, local field potential spectral bands - specifically theta, beta, and gamma frequency ranges - encoded immediately available rewards but not time costs. The disjunction between information contained in spiking and local field potentials can constrain models of foraging-related processing. In particular, given the proposed link between local field potentials and inputs to a brain area, it raises the possibility that local processing within dorsal anterior cingulate sulcus serves to more fully bind immediate reward and time costs into a single decision variable.

为了使长期奖励率最大化,觅食者决定何时离开一个斑块必须计算一个决策变量,这个决策变量既反映了立即可用的奖励,也反映了前往下一个斑块的时间成本。确定调解这种计算的机制是理解大脑如何执行觅食决策的核心。我们以前表明,背前扣带沟神经元的放电率包含这两个变量。这一结果并没有提供信息,是否反映在背前扣带沟峰活动的信息整合是局部发生的,还是从上游结构遗传而来。在这里,我们检查了与早期记录同时收集的局部场电位。在大多数记录地点,局部场电位谱带-特别是theta, beta和gamma频率范围-编码立即可用的奖励,而不是时间成本。峰值信息和局部场电位之间的脱节可能会限制觅食相关加工模型。特别是,考虑到局部场电位和大脑区域输入之间的联系,它提出了一种可能性,即在背前扣带沟内的局部处理有助于更充分地将即时奖励和时间成本绑定到一个单一的决策变量中。
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引用次数: 9
Remembering the order of serially presented objects: A matter of time? 记住按顺序呈现的物体的顺序:时间问题?
Pub Date : 2019-01-01 DOI: 10.1177/2398212819883088
G. Barker, O. Evuarherhe, E. Warburton
Remembering the sequence, in which stimuli are encountered or events have occurred, is a key process in episodic memory and can also facilitate recognition memory. Rodents, when presented with a sequence of objects, will explore the object encountered first; yet, whether this behaviour is because the rodents spontaneously encode the order of stimuli presentation or because of relative familiarity or temporal decay is unknown. Here, we tested sequence memory in rats using a series of spontaneous preference tasks. Experiment 1 demonstrated that when rats are presented with a sequence of four objects, with an inter-sample interval of 5 min or 1 h, they preferentially explored the object presented earlier in the list irrespective of the inter-sample interval. We then demonstrated that such memory for order was not affected by increasing or decreasing the inter-sample interval between the middle objects (Experiment 2). Finally, we showed that memory for order is not a function of absolute object familiarity, as animals showed clear discrimination between the objects presented in the sample phases and a novel object, independent of the sample objects’ position in the sequence (Experiment 3). These results show that animals are able to encode the order of objects presented in a sequence, and as such temporal order memory is not achieved using the process of relative or absolute familiarity or temporal decay.
记住遇到刺激或事件发生的顺序,是情景记忆的一个关键过程,也可以促进识别记忆。当啮齿类动物看到一系列物体时,它们会先探索遇到的物体;然而,这种行为是由于啮齿类动物自发地对刺激呈现的顺序进行编码,还是由于相对熟悉或时间衰退,目前尚不清楚。在这里,我们使用一系列自发偏好任务来测试大鼠的序列记忆。实验1表明,当以5分钟或1小时的样本间隔向大鼠展示一个由四个物体组成的序列时,它们优先探索列表中较早出现的物体,而与样本间隔无关。然后,我们证明了这种顺序记忆不受中间物体之间样本间隔的增加或减少的影响(实验2)。最后,我们证明了顺序记忆不是物体绝对熟悉度的函数,因为动物在样本阶段呈现的物体和新物体之间表现出明显的区分。实验3)。这些结果表明,动物能够对序列中出现的物体的顺序进行编码,因此,时间顺序记忆不是通过相对或绝对熟悉或时间衰减过程实现的。
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引用次数: 6
Mapping the impact of exposure to maternal immune activation on juvenile Wistar rat brain macro- and microstructure during early post-natal development 产后早期暴露于母体免疫激活对幼年Wistar大鼠大脑宏观和微观结构的影响
Pub Date : 2019-01-01 DOI: 10.1177/2398212819883086
Tobias C. Wood, Michelle E. Edye, M. Harte, J. Neill, E. Prinssen, A. Vernon
Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid–induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.
母体免疫激活始终与受影响后代患多种精神疾病的风险升高有关。与此相关,我们工作的一个重要目标是探索母体免疫激活效应在整个寿命中的影响。在这方面,我们最近报道了多核糖肌苷-多核糖胞苷酸在妊娠第15天、出生前、妊娠第21天和产后第21天诱导的母体免疫激活的作用,提供了血浆白细胞介素6的系统评估,妊娠大鼠的体温和体重变化,以及在这些时间点雄性和雌性后代的大体形态学变化和小胶质细胞神经病理学的初步证据。在这里,我们试图通过使用高分辨率离体解剖磁共振成像结合基于图谱的分割,更详细地描述妊娠第15天妊娠期多核糖肌苷酸-多核糖胞苷酸暴露对幼年(出生后第21天)大鼠大脑神经解剖学的中尺度影响,来补充和扩展这些数据。我们的初步数据表明,妊娠期多核糖肌苷-多核糖胞苷酸暴露(n = 10) 相对于生理盐水对照(n = 10) 在这个时间点。具体而言,我们发现在多核糖肌苷-多核糖胞苷酸后代中对角线结构域的相对体积增加(p < 0.01未校正),只是未能通过严格的多重比较校正(实际q = 0.07)。使用扩散张量成像未检测到统计学上显著的微观结构变化。需要进一步的研究来绘制母体免疫激活对从胎儿到产后早期发育中的啮齿动物大脑的近端影响,并证实我们的研究结果。
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引用次数: 3
Deep brain stimulation: An overview of history, methods, and future developments. 脑深部刺激:历史、方法和未来发展综述。
Pub Date : 2018-12-12 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818816017
Laurie Pycroft, John Stein, Tipu Aziz

Deep brain stimulation has already revolutionised the clinical management of treatment-resistant movement disorders and offers novel treatment options for an increasing range of neurological and psychiatric illnesses. In this article, we briefly review the history of deep brain stimulation, particularly focusing on the last 50 years, which have seen rapid development in the safety and efficacy of deep brain stimulation. We then discuss the current state of the art in deep brain stimulation, focusing on emerging indications and recent technological advances that have improved the field. Finally, we consider the future developments in technology, technique, and research that will impact deep brain stimulation; particularly focusing on closed-loop stimulation techniques and emerging techniques such as optogenetics, cybersecurity risk, implantation timing, and impediments to undertaking high-quality research.

脑深部刺激已经彻底改变了难治性运动障碍的临床管理,并为越来越多的神经和精神疾病提供了新的治疗选择。在本文中,我们简要回顾了脑深部刺激的历史,特别是近50年来,脑深部刺激在安全性和有效性方面取得了快速发展。然后,我们将讨论深部脑刺激技术的现状,重点关注新出现的适应症和最近的技术进步,这些都改善了该领域。最后,我们考虑了影响深部脑刺激的技术、技术和研究的未来发展;特别关注闭环刺激技术和新兴技术,如光遗传学,网络安全风险,植入时机,以及进行高质量研究的障碍。
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引用次数: 46
Neuroengineering and neuroprosthetics. 神经工程和神经修复学。
Pub Date : 2018-12-12 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818817499
Kevin Warwick

This article contains a directed overview of the field of neuroengineering and neuroprosthetics. The aim of the article is, however, not to go over introductory material covered elsewhere, but rather to look ahead at exciting areas for likely future development. The BrainGate implant is focussed on in terms of its use as an interface between the Internet and the human nervous system. Sensory prosthetics of different types and deep brain stimulation are considered. Different possibilities with deep brain stimulation are also discussed.

这篇文章包含了神经工程和神经修复领域的直接概述。然而,本文的目的不是回顾其他地方介绍的介绍性材料,而是展望未来可能开发的令人兴奋的领域。BrainGate植入物的重点是作为互联网和人类神经系统之间的接口。考虑了不同类型的感觉假肢和深部脑刺激。还讨论了深部脑刺激的不同可能性。
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引用次数: 7
Antibody-mediated central nervous system diseases. 抗体介导的中枢神经系统疾病。
Pub Date : 2018-12-10 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818817497
Maria Pia Giannoccaro, Sarah J Crisp, Angela Vincent

Antibody-mediated central nervous system diseases are a relatively new area of clinical neuroscience with growing impact. Their recognition has challenged the dogma of the blood-brain barrier preventing antibody access into the central nervous system. The antibodies discovered so far are mainly against neurotransmitter receptors (e.g. N-methyl-d-aspartate and glycine receptors) and ion channel-associated proteins (leucine-rich glioma inactivated protein 1 and contactin-associated protein 2) and are expressed on the surface of neuronal synapses and elsewhere. The disorders are reversible with immunotherapies that reduce antibody levels. Although rare, the identification of these disorders in clinical practice has made central nervous system autoimmune diseases a consideration in the differential diagnoses of many clinical presentations. There is still much to learn about the aetiology of the diseases and the mechanisms by which the antibodies act, the neuronal and glial changes that follow antibody-attack, and the compensatory changes that may be required to ensure good recovery.

抗体介导的中枢神经系统疾病是临床神经科学的一个相对较新的领域,影响越来越大。他们的发现挑战了血脑屏障阻止抗体进入中枢神经系统的教条。目前发现的抗体主要针对神经递质受体(如n-甲基-d-天冬氨酸和甘氨酸受体)和离子通道相关蛋白(富含亮氨酸的胶质瘤失活蛋白1和接触蛋白2),并在神经元突触表面和其他地方表达。通过降低抗体水平的免疫疗法,这些疾病是可逆的。虽然罕见,但在临床实践中,这些疾病的识别使中枢神经系统自身免疫性疾病成为许多临床表现鉴别诊断的考虑因素。关于这些疾病的病因、抗体的作用机制、抗体攻击后神经元和神经胶质的变化,以及确保良好恢复所需的代偿性变化,还有很多东西需要了解。
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引用次数: 12
Invertebrate models of behavioural plasticity and human disease. 行为可塑性和人类疾病的无脊椎动物模型。
Pub Date : 2018-12-07 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818818068
Lindy Holden-Dye, Robert J Walker

The fundamental processes of neural communication have been largely conserved through evolution. Throughout the last century, researchers have taken advantage of this, and the experimental tractability of invertebrate animals, to advance understanding of the nervous system that translates to mammalian brain. This started with the inspired analysis of the ionic basis of neuronal excitability and neurotransmission using squid during the 1940s and 1950s and has progressed to detailed insight into the molecular architecture of the synapse facilitated by the genetic tractability of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Throughout this time, invertebrate preparations have provided a means to link neural mechanisms to behavioural plasticity and thus key insight into fundamental aspects of control systems, learning, and memory. This article captures key highlights that exemplify the historical and continuing invertebrate contribution to neuroscience.

神经通讯的基本过程在很大程度上是通过进化保存下来的。在上个世纪,研究人员一直在利用这一点,以及无脊椎动物的实验可驯服性,来推进对神经系统的理解,从而转化为哺乳动物的大脑。这始于20世纪40年代和50年代对鱿鱼神经元兴奋性和神经传递的离子基础的启发分析,并通过线虫秀丽隐杆线虫和果蝇果蝇的遗传易感性促进了对突触分子结构的详细了解。在这段时间里,无脊椎动物的准备工作提供了一种将神经机制与行为可塑性联系起来的方法,从而对控制系统、学习和记忆的基本方面有了关键的了解。这篇文章抓住了历史和持续的无脊椎动物对神经科学的贡献的关键亮点。
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引用次数: 6
Purine and purinergic receptors. 嘌呤和嘌呤能受体。
Pub Date : 2018-12-06 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818817494
Geoffrey Burnstock

Adenosine 5'-triphosphate acts as an extracellular signalling molecule (purinergic signalling), as well as an intracellular energy source. Adenosine 5'-triphosphate receptors have been cloned and characterised. P1 receptors are selective for adenosine, a breakdown product of adenosine 5'-triphosphate after degradation by ectonucleotidases. Four subtypes are recognised, A1, A2A, A2B and A3 receptors. P2 receptors are activated by purine and by pyrimidine nucleotides. P2X receptors are ligand-gated ion channel receptors (seven subunits (P2X1-7)), which form trimers as both homomultimers and heteromultimers. P2Y receptors are G protein-coupled receptors (eight subtypes (P2Y1/2/4/6/11/12/13/14)). There is both purinergic short-term signalling and long-term (trophic) signalling. The cloning of P2X-like receptors in primitive invertebrates suggests that adenosine 5'-triphosphate is an early evolutionary extracellular signalling molecule. Selective purinoceptor agonists and antagonists with therapeutic potential have been developed for a wide range of diseases, including thrombosis and stroke, dry eye, atherosclerosis, kidney failure, osteoporosis, bladder incontinence, colitis, neurodegenerative diseases and cancer.

腺苷5'-三磷酸作为细胞外信号分子(嘌呤能信号),以及细胞内的能量来源。腺苷5'-三磷酸受体已克隆并鉴定。P1受体对腺苷具有选择性,腺苷是5'-三磷酸腺苷被外核苷酶降解后的分解产物。四种亚型被识别,A1, A2A, A2B和A3受体。P2受体被嘌呤和嘧啶核苷酸激活。P2X受体是配体门控离子通道受体(7个亚基(P2X1-7)),它们形成三聚体,既可以是同聚体,也可以是异聚体。P2Y受体是G蛋白偶联受体(8种亚型(P2Y1/2/4/6/11/12/13/14))。嘌呤能短期信号传导和长期(营养)信号传导都存在。原始无脊椎动物p2x样受体的克隆表明腺苷5'-三磷酸是一种早期进化的细胞外信号分子。具有治疗潜力的选择性嘌呤受体激动剂和拮抗剂已被开发用于广泛的疾病,包括血栓形成和中风、干眼症、动脉粥样硬化、肾衰竭、骨质疏松症、膀胱失禁、结肠炎、神经退行性疾病和癌症。
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引用次数: 179
The development of antipsychotic drugs. 抗精神病药物的开发。
Pub Date : 2018-12-05 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818817498
David Cunningham Owens, Eve C Johnstone

Antipsychotic drugs revolutionised psychiatric practice and provided a range of tools for exploring brain function in health and disease. Their development and introduction were largely empirical but based on long and honourable scientific credentials and remarkable powers of clinical observation. The class shares a common core action of attenuating central dopamine transmission, which underlies the major limitation to their use - high liability to disrupt extrapyramidal function - and also the most durable hypothesis of the basis of psychotic disorders, especially schizophrenia. However, the Dopamine Hypothesis, which has driven drug development for almost half a century, has become a straight-jacket, stifling innovation, resulting in a class of compounds that are largely derivative. Recent efforts only cemented this tendency as no clinical evidence supports the notion that newer compounds, modelled on clozapine, share that drug's unique neurological tolerability and can be considered 'atypical'. Patients and doctors alike must await a more profound understanding of central dopamine homeostasis and novel methods of maintaining it before they can again experience the intoxicating promise antipsychotics once held.

抗精神病药物彻底改变了精神病治疗方法,并为探索健康和疾病中的大脑功能提供了一系列工具。抗精神病药物的开发和引入主要是经验性的,但其基础却是长期而光荣的科学资历和非凡的临床观察能力。这类药物有一个共同的核心作用,即减弱中枢多巴胺的传递,这也是其使用的主要局限性--极易破坏锥体外系功能--的基础,同时也是关于精神障碍,尤其是精神分裂症基础的最持久的假说。然而,多巴胺假说推动了近半个世纪的药物研发,却成为一种束缚,扼杀了创新,导致这类化合物在很大程度上是衍生产品。最近的努力只是巩固了这一趋势,因为没有临床证据支持这样一种观点,即以氯氮平为蓝本的新化合物具有氯氮平独特的神经耐受性,可以被视为 "非典型 "药物。患者和医生都必须等待对中枢多巴胺稳态和维持多巴胺稳态的新方法有更深刻的理解后,才能再次体验到抗精神病药物曾经带来的令人陶醉的希望。
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引用次数: 0
The utility of stem cells for neural regeneration. 干细胞在神经再生中的应用。
Pub Date : 2018-12-05 eCollection Date: 2018-01-01 DOI: 10.1177/2398212818818071
Kirsty Goncalves, Stefan Przyborski

The use of stem cells in biomedical research is an extremely active area of science. This is because they provide tools that can be used both in vivo and vitro to either replace cells lost in degenerative processes, or to model such diseases to elucidate their underlying mechanisms. This review aims to discuss the use of stem cells in terms of providing regeneration within the nervous system, which is particularly important as neurons of the central nervous system lack the ability to inherently regenerate and repair lost connections. As populations are ageing, incidence of neurodegenerative diseases are increasing, highlighting the need to better understand the regenerative capacity and many uses of stem cells in this field.

干细胞在生物医学研究中的应用是一个非常活跃的科学领域。这是因为它们提供的工具既可以在体内使用,也可以在体外使用,以替代在退行性过程中丢失的细胞,或者对这类疾病进行建模,以阐明其潜在机制。这篇综述旨在讨论干细胞在神经系统内提供再生方面的应用,这在中枢神经系统的神经元缺乏固有的再生和修复失去的连接的能力时尤为重要。随着人口老龄化,神经退行性疾病的发病率正在增加,这突出表明需要更好地了解再生能力和干细胞在这一领域的许多用途。
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引用次数: 5
期刊
Brain and neuroscience advances
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