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A data augmentation procedure to improve detection of spike ripples in brain voltage recordings. 改进脑电压记录中尖峰波纹检测的数据增强程序。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-03 DOI: 10.1016/j.neures.2024.07.005
Emily D Schlafly, Daniel Carbonero, Catherine J Chu, Mark A Kramer

Epilepsy is a major neurological disorder characterized by recurrent, spontaneous seizures. For patients with drug-resistant epilepsy, treatments include neurostimulation or surgical removal of the epileptogenic zone (EZ), the brain region responsible for seizure generation. Precise targeting of the EZ requires reliable biomarkers. Spike ripples - high-frequency oscillations that co-occur with large amplitude epileptic discharges - have gained prominence as a candidate biomarker. However, spike ripple detection remains a challenge. The gold-standard approach requires an expert manually visualize and interpret brain voltage recordings, which limits reproducibility and high-throughput analysis. Addressing these limitations requires more objective, efficient, and automated methods for spike ripple detection, including approaches that utilize deep neural networks. Despite advancements, dataset heterogeneity and scarcity severely limit machine learning performance. Our study explores long-short term memory (LSTM) neural network architectures for spike ripple detection, leveraging data augmentation to improve classifier performance. We highlight the potential of combining training on augmented and in vivo data for enhanced spike ripple detection and ultimately improving diagnostic accuracy in epilepsy treatment.

癫痫是一种主要的神经系统疾病,其特点是反复、自发的癫痫发作。对于耐药性癫痫患者,治疗方法包括神经刺激或手术切除致痫区(EZ),即导致癫痫发作的脑区。要精确定位 EZ 需要可靠的生物标志物。尖峰波纹--与大振幅癫痫放电同时出现的高频振荡--作为一种候选生物标志物已逐渐受到重视。然而,尖峰波纹检测仍然是一项挑战。金标准方法需要专家手动观察和解释脑电压记录,这限制了可重复性和高通量分析。要解决这些局限性,需要更客观、高效和自动化的尖峰波纹检测方法,包括利用深度神经网络的方法。尽管取得了进步,但数据集的异质性和稀缺性严重限制了机器学习的性能。我们的研究探索了用于尖峰波纹检测的长短期记忆(LSTM)神经网络架构,利用数据增强来提高分类器性能。我们强调了在增强数据和活体数据上结合训练以增强尖峰波纹检测并最终提高癫痫治疗诊断准确性的潜力。
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引用次数: 0
Inference of monosynaptic connections from parallel spike trains: A review. 从平行尖峰序列推断单突触连接:综述。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-02 DOI: 10.1016/j.neures.2024.07.006
Ryota Kobayashi, Shigeru Shinomoto

This article presents a mini-review about the progress in inferring monosynaptic connections from spike trains of multiple neurons over the past twenty years. First, we explain a variety of meanings of "neuronal connectivity" in different research areas of neuroscience, such as structural connectivity, monosynaptic connectivity, and functional connectivity. Among these, we focus on the methods used to infer the monosynaptic connectivity from spike data. We then summarize the inference methods based on two main approaches, i.e., correlation-based and model-based approaches. Finally, we describe available source codes for connectivity inference and future challenges. Although inference will never be perfect, the accuracy of identifying the monosynaptic connections has improved dramatically in recent years due to continuous efforts.

本文简要回顾了过去二十年来从多个神经元的尖峰序列推断单突触连接的研究进展。首先,我们解释了神经科学不同研究领域中 "神经元连接 "的各种含义,如结构连接、单突触连接和功能连接。其中,我们重点关注从尖峰数据推断单突触连通性的方法。然后,我们总结了基于两种主要方法的推断方法,即基于相关性的方法和基于模型的方法。最后,我们介绍了用于连接性推断的可用源代码以及未来的挑战。尽管推断永远不可能完美无缺,但经过近年来的不断努力,识别单突触连接的准确性已经有了显著提高。
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引用次数: 0
Neuronal activity in the anterior paraventricular nucleus of thalamus positively correlated with sweetener consumption in mice 丘脑前室旁核的神经元活动与小鼠甜味剂摄入量呈正相关。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 DOI: 10.1016/j.neures.2024.02.002

Although the brain can discriminate between various sweet substances, the underlying neural mechanisms of this complex behavior remain elusive. This study examines the role of the anterior paraventricular nucleus of the thalamus (aPVT) in governing sweet preference in mice. We fed the mice six different diets with equal sweetness for six weeks: control diet (CD), high sucrose diet (HSD), high stevioside diet (HSSD), high xylitol diet (HXD), high glycyrrhizin diet (HGD), and high mogroside diet (HMD). The mice exhibited a marked preference specifically for the HSD and HSSD. Following consumption of these diets, c-Fos expression levels in the aPVT were significantly higher in these two groups compared to the others. Utilizing fiber photometry calcium imaging, we observed rapid activation of aPVT neurons in response to sucrose and stevioside intake, but not to xylitol or water. Our findings suggest that aPVT activity aligns with sweet preference in mice, and notably, stevioside is the sole plant-based sweetener that elicits an aPVT response comparable to that of sucrose.

虽然大脑可以分辨各种甜味物质,但这种复杂行为的潜在神经机制仍然难以捉摸。本研究探讨了丘脑前室旁核(aPVT)在支配小鼠甜味偏好中的作用。我们给小鼠喂食了六周甜度相同的六种不同食物:对照组食物(CD)、高蔗糖食物(HSD)、高甜菊糖苷食物(HSSD)、高木糖醇食物(HXD)、高甘草苷食物(HGD)和高木糖醇苷食物(HMD)。小鼠表现出对 HSD 和 HSSD 的明显偏好。食用这些食物后,这两组小鼠 aPVT 中的 c-Fos 表达水平明显高于其他组。利用纤维光度钙成像技术,我们观察到 aPVT 神经元在摄入蔗糖和甜菊糖苷后迅速激活,而在摄入木糖醇或水后则没有激活。我们的研究结果表明,aPVT 活性与小鼠的甜味偏好一致,而且值得注意的是,甜菊糖苷是唯一能引起与蔗糖相当的 aPVT 反应的植物甜味剂。
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引用次数: 0
Transient sleep apnea results in long-lasting increase in β-amyloid generation and tau hyperphosphorylation 短暂的睡眠呼吸暂停会导致β-淀粉样蛋白生成和tau过度磷酸化的长期增加。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 DOI: 10.1016/j.neures.2024.03.003

Sleep apnea is regarded as an important risk factor in the pathogenesis of Alzheimer disease (AD). Chronic intermittent hypoxia treatment (IHT) given during the sleep period of the circadian cycle in experimental animals is a well-established sleep apnea model. Here we report that transient IHT for 4 days on AD model mice causes Aβ overproduction 2 months after IHT presumably via upregulation of synaptic BACE1, side-by-side with tau hyperphosphorylation. These results suggest that even transient IHT may be sufficient to cause long-lasting changes in the molecules measured as AD biomarkers in the brain.

睡眠呼吸暂停被认为是阿尔茨海默病(AD)发病机制中的一个重要风险因素。在实验动物昼夜节律周期的睡眠期给予慢性间歇性缺氧治疗(IHT)是一种行之有效的睡眠呼吸暂停模型。在此,我们报告了对AD模型小鼠进行为期4天的短暂间歇性缺氧治疗会导致Aβ在间歇性缺氧治疗2个月后过度生成,这可能是通过突触BACE1的上调以及tau的过度磷酸化实现的。这些结果表明,即使是短暂的 IHT 也足以导致大脑中作为 AD 生物标志物的分子发生长期变化。
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引用次数: 0
The serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project to the dorsal pallium in zebrafish 源自菱形丘 2 的血清素能神经元定位于斑马鱼的正中剑突区,并投射到背侧丘。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 DOI: 10.1016/j.neures.2024.03.001

The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning.

剑突核中的血清素能神经元与学习和情感等多种认知功能有关。在脊椎动物中,剑突核分为背侧剑突和正中剑突。与背侧剑突功能的丰富知识相比,中侧剑突的血清素能神经元的作用相对未知。利用斑马鱼进行的研究发现,正中饶舌神经元的血清素能神经元接受来自哈贝纳拉和IPN两条不同通路的输入。利用斑马鱼可能会揭示 Hb-IPN- 正中急腹症通路的功能。要弄清正中饶舌区血清素能神经元的功能,有必要将它们与背侧饶舌区的神经元区分开来。在小鼠中,大多数正中饶舌5-羟色胺能神经元起源于菱形丘2,而我们产生的转基因斑马鱼可以标记菱形丘2的5-羟色胺能神经元。在这项研究中,我们发现源自菱形丘2的5-羟色胺能神经元定位于斑马鱼的正中饶舌,并将轴突投射到喙背掌叶。这项研究表明,这种转基因系统有可能特异性地揭示 Hb-IPN- 油菜-延脑回路在学习中的功能和信息处理。
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引用次数: 0
Fatty acid amides present in Camembert cheese improved cognitive decline after oral administration in mice 金文奶酪中的脂肪酸酰胺改善了小鼠口服后认知能力的下降。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 DOI: 10.1016/j.neures.2024.03.002

Herein, we investigated the effects of Camembert cheese (CC) and its fatty acid contents on cognitive function in mice by employing the object recognition test to evaluate hippocampus-dependent memory. Orally administered CC improved the cognitive decline induced by a high-fat diet. Next, we focused on myristamide (MA), oleamide, and stearamide, which are fatty acid amides produced during the fermentation process of CC. We found that oral administration of MA improved cognitive decline. Notably, an improvement was not observed using myristic acid, a free fatty acid that is not amidated. Thus, fatty acid amidation may contribute to the physiological activity. Moreover, we investigated changes in gene expression related to neurogenesis in the hippocampus. After MA administration, mRNA expression analysis indicated that MA increased hippocampal brain-derived neurotrophic factor expression.

在此,我们通过使用物体识别测试评估海马依赖性记忆,研究了卡门培尔奶酪(CC)及其脂肪酸含量对小鼠认知功能的影响。口服CC可改善高脂饮食引起的认知功能下降。接下来,我们重点研究了肉豆蔻酰胺(MA)、油酰胺和硬脂酰胺,它们是在CC发酵过程中产生的脂肪酸酰胺。我们发现,口服肉豆蔻酰胺可改善认知能力下降。值得注意的是,使用肉豆蔻酸(一种未被酰胺化的游离脂肪酸)却没有观察到改善作用。因此,脂肪酸酰胺化可能有助于提高其生理活性。此外,我们还研究了与海马神经发生相关的基因表达变化。服用 MA 后,mRNA 表达分析表明 MA 增加了海马脑源性神经营养因子的表达。
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引用次数: 0
Anxiety control by astrocytes in the lateral habenula 侧叶星形胶质细胞对焦虑的控制
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 DOI: 10.1016/j.neures.2024.01.006

The potential role of astrocytes in lateral habenula (LHb) in modulating anxiety was explored in this study. The habenula are a pair of small nuclei located above the thalamus, known for their involvement in punishment avoidance and anxiety. Herein, we observed an increase in theta-band oscillations of local field potentials (LFPs) in the LHb when mice were exposed to anxiety-inducing environments. Electrical stimulation of LHb at theta-band frequency promoted anxiety-like behavior. Calcium (Ca2+) levels and pH in the cytosol of astrocytes and local brain blood volume changes were studied in mice expressing either a Ca2+ or a pH sensor protein specifically in astrocytes and mScarlet fluorescent protein in the blood plasma using fiber photometry. An acidification response to anxiety was observed. Photoactivation of archaerhopsin-T (ArchT), an optogenetic tool that acts as an outward proton pump, results in intracellular alkalinization. Photostimulation of LHb in astrocyte-specific ArchT-expressing mice resulted in dissipation of theta-band LFP oscillation in an anxiogenic environment and suppression of anxiety-like behavior. These findings provide evidence that LHb astrocytes modulate anxiety and may offer a new target for treatment of anxiety disorders.

本研究探讨了星形胶质细胞在侧脑室(LHb)中调节焦虑的潜在作用。外侧神经节是位于丘脑上方的一对小核团,因参与惩罚回避和焦虑而闻名。在本研究中,我们观察到当小鼠暴露在焦虑诱导环境中时,LHb局部场电位(LFPs)的θ波段振荡增加。以θ波段频率电刺激LHb可促进焦虑样行为。使用纤维光度计研究了在星形胶质细胞中特异表达 Ca2+ 或 pH 传感器蛋白的小鼠和在血浆中表达 mScarlet 荧光蛋白的小鼠的星形胶质细胞胞浆中钙(Ca2+)水平和 pH 值以及局部脑血量的变化。观察到了焦虑的酸化反应。光激活作为外向质子泵的光遗传工具 archaerhopsin-T(ArchT)会导致细胞内碱化。光刺激星形胶质细胞特异性表达 ArchT 的小鼠体内的 LHb 会导致焦虑环境中的θ波段 LFP 振荡消散,并抑制焦虑样行为。这些发现提供了 LHb 星形胶质细胞调节焦虑的证据,并可能为焦虑症的治疗提供一个新的靶点。
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引用次数: 0
Estimation of firing rate from instantaneous interspike intervals. 从瞬时间隔估算发射率
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-06-24 DOI: 10.1016/j.neures.2024.06.006
Lubomir Kostal, Kristyna Kovacova

The rate coding hypothesis is the oldest and still one of the most accepted hypotheses of neural coding. Consequently, many approaches have been devised for the firing rate estimation, ranging from simple binning of the time axis to advanced statistical methods. Nonetheless the concept of firing rate, while informally understood, can be mathematically defined in several distinct ways. These definitions may yield mutually incompatible results unless implemented properly. Recently it has been shown that the notions of the instantaneous and the classical firing rates can be made compatible, at least in terms of their averages, by carefully discerning the time instant at which the neuronal activity is observed. In this paper we revisit the properties of instantaneous interspike intervals in order to derive several novel firing rate estimators, which are free of additional assumptions or parameters and their temporal resolution is 'locally self-adaptive'. The estimators are simple to implement and are numerically efficient even for very large sets of data.

速率编码假说是最古老的神经编码假说,也是目前最被接受的假说之一。因此,人们设计了许多方法来估计发射率,从简单的时间轴分档到先进的统计方法,不一而足。然而,尽管对发射率的概念有非正式的理解,但在数学上却有几种不同的定义。这些定义如果不能正确执行,可能会产生互不兼容的结果。最近的研究表明,通过仔细辨别观察神经元活动的时间瞬间,可以使瞬时发射率和经典发射率的概念相容,至少就其平均值而言是如此。在本文中,我们重新审视了瞬时棘间间隔的特性,从而推导出几种新的发射率估计器,它们不需要额外的假设或参数,其时间分辨率是 "局部自适应 "的。这些估计器的实现非常简单,即使在数据量非常大的情况下也能有效计算。
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引用次数: 0
Volume electron microscopy for genetically and molecularly defined neural circuits. 用于基因和分子定义神经回路的体电子显微镜。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-06-22 DOI: 10.1016/j.neures.2024.06.002
Nobuhiko Ohno, Fuyuki Karube, Fumino Fujiyama

The brain networks responsible for adaptive behavioral changes are based on the physical connections between neurons. Light and electron microscopy have long been used to study neural projections and the physical connections between neurons. Volume electron microscopy has recently expanded its scale of analysis due to methodological advances, resulting in complete wiring maps of neurites in a large volume of brain tissues and even entire nervous systems in a growing number of species. However, structural approaches frequently suffer from inherent limitations in which elements in images are identified solely by morphological criteria. Recently, an increasing number of tools and technologies have been developed to characterize cells and cellular components in the context of molecules and gene expression. These advancements include newly developed probes for visualization in electron microscopic images as well as correlative integration methods for the same elements across multiple microscopic modalities. Such approaches advance our understanding of interactions between specific neurons and circuits and may help to elucidate novel aspects of the basal ganglia network involving dopamine neurons. These advancements are expected to reveal mechanisms for processing adaptive changes in specific neural circuits that modulate brain functions.

负责适应性行为变化的大脑网络基于神经元之间的物理连接。长期以来,人们一直使用光学显微镜和电子显微镜来研究神经投射和神经元之间的物理连接。最近,由于方法学的进步,体层电子显微镜扩大了其分析范围,在越来越多的物种中,大量脑组织甚至整个神经系统中都出现了神经元的完整布线图。然而,结构方法经常受到固有局限性的影响,即仅根据形态学标准识别图像中的元素。最近,越来越多的工具和技术被开发出来,用于根据分子和基因表达来描述细胞和细胞成分的特征。这些进步包括新开发的用于电子显微镜图像可视化的探针,以及在多种显微模式下对相同元素进行相关整合的方法。这些方法有助于加深我们对特定神经元和回路之间相互作用的理解,并有助于阐明基底神经节网络中涉及多巴胺神经元的新方面。这些进展有望揭示调节大脑功能的特定神经回路适应性变化的处理机制。
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引用次数: 0
Large-scale foundation models and generative AI for BigData neuroscience. 用于大数据神经科学的大规模基础模型和生成式人工智能。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-06-17 DOI: 10.1016/j.neures.2024.06.003
Ran Wang, Zhe Sage Chen

Recent advances in machine learning have led to revolutionary breakthroughs in computer games, image and natural language understanding, and scientific discovery. Foundation models and large-scale language models (LLMs) have recently achieved human-like intelligence thanks to BigData. With the help of self-supervised learning (SSL) and transfer learning, these models may potentially reshape the landscapes of neuroscience research and make a significant impact on the future. Here we present a mini-review on recent advances in foundation models and generative AI models as well as their applications in neuroscience, including natural language and speech, semantic memory, brain-machine interfaces (BMIs), and data augmentation. We argue that this paradigm-shift framework will open new avenues for many neuroscience research directions and discuss the accompanying challenges and opportunities.

机器学习的最新进展为计算机游戏、图像和自然语言理解以及科学发现带来了革命性的突破。得益于 BigData,基础模型和大规模语言模型(LLMs)最近实现了类似人类的智能。在自我监督学习(SSL)和迁移学习的帮助下,这些模型有可能重塑神经科学研究的格局,并对未来产生重大影响。在此,我们将对基础模型和生成式人工智能模型的最新进展及其在神经科学中的应用做一个小型回顾,包括自然语言和语音、语义记忆、脑机接口(BMI)和数据增强。我们认为,这种范式转换框架将为许多神经科学研究方向开辟新的途径,并讨论了随之而来的挑战和机遇。
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引用次数: 0
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