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The role of TRPV4 in acute sleep deprivation-induced fear memory impairment TRPV4 在急性睡眠剥夺诱发的恐惧记忆损伤中的作用
Pub Date : 2024-08-12 DOI: 10.1101/2024.08.12.607531
Meimei Guo, Feiyang Zhang, Sha Liu, Yi Zhang, Lesheng Wang, Jian Song, Wei Wei, Xiang Li
Acute sleep deprivation (ASD) negatively impacts fear memory, but the underlying mechanisms are not fully understood. Transient receptor potential vanilloid 4 (TRPV4), a cation channel which is closely correlated with the concentration of Ca2+, and neuronal Ca2+ overloading is a crucial inducement of learning and memory impairment. This study utilized an acute sleep-deprived mouse model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed increased expression of TRPV4 in mice with ASD-induced fear memory impairment. Notably, knockdown of TRPV4 reversed ASD-induced fear memory impairment. ASD leads to the increased concentration of Ca2+. Additionally, we observed a reduction in spine density and a significant decrease in postsynaptic density protein 95 (PSD95), which is associated with synaptic plasticity, in sleep-deprived fear memory impairment mice. This indicates that ASD may cause overloaded Ca2+, disrupting synaptic plasticity and impairing fear memory. Moreover, TRPV4 knockdown significantly decreased Ca2+ concentration, mitigated the loss of dendritic spines and reduction of PSD95, contributing to the restoration of fear memory. These findings indicate a potential protective role of TRPV4 knockdown in counteracting ASD-induced fear memory deficits. Collectively, our results highlight that TRPV4 may be a potential therapeutic target in mediating fear memory impairment due to ASD and underscore the importance of sleep management for conditions like PTSD.
急性睡眠剥夺(ASD)会对恐惧记忆产生负面影响,但其潜在机制尚不完全清楚。瞬时受体电位类香草素4(TRPV4)是一种与Ca2+浓度密切相关的阳离子通道,神经元Ca2+超载是诱发学习和记忆障碍的关键因素。本研究利用急性睡眠剥夺小鼠模型结合恐惧条件反射来研究这些机制。mRNA测序显示,在ASD诱导的恐惧记忆损伤小鼠中,TRPV4的表达增加。值得注意的是,TRPV4的敲除可逆转ASD诱导的恐惧记忆损伤。ASD 会导致 Ca2+ 浓度升高。此外,我们还观察到睡眠不足的恐惧记忆受损小鼠脊柱密度降低,与突触可塑性相关的突触后密度蛋白95(PSD95)显著减少。这表明 ASD 可能会导致 Ca2+ 过载,破坏突触可塑性并损害恐惧记忆。此外,TRPV4基因敲除可显著降低Ca2+浓度,缓解树突棘的缺失和PSD95的减少,有助于恐惧记忆的恢复。这些发现表明,TRPV4敲除在抵消ASD诱导的恐惧记忆缺陷方面具有潜在的保护作用。总之,我们的研究结果强调了TRPV4可能是介导ASD引起的恐惧记忆障碍的潜在治疗靶点,并强调了睡眠管理对创伤后应激障碍等疾病的重要性。
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引用次数: 0
Functional Electrical Stimulation and Brain-Machine Interfaces for Simultaneous Control of Wrist and Finger Flexion 同时控制手腕和手指屈伸的功能性电刺激和脑机接口
Pub Date : 2024-08-12 DOI: 10.1101/2024.08.11.607263
Matthew J Mender, Ayobami L Ward, Luis H Cubillos, Madison M Kelberman, Joseph T Costello, Hisham Temmar, Dylan M Wallace, Edanjen T Lin, Jordan L W Lam, Matthew S Willsey, Nishant Ganesh Kumar, Theodore A Kung, Parag G Patil, Cynthia A Chestek
Brain-machine interface (BMI) controlled functional electrical stimulation (FES) is a promising treatment to restore hand movements to people with cervical spinal cord injury. Recent intracortical BMIs have shown unprecedented successes in decoding user intentions, however the hand movements restored by FES have largely been limited to predetermined grasps. Restoring dexterous hand movements will require continuous control of many biomechanically linked degrees-of-freedom in the hand, such as wrist and finger flexion, that would form the basis of those movements. Here we investigate the ability to restore simultaneous wrist and finger flexion, which would enable grasping with a controlled hand posture and assist in manipulating objects once grasped. We demonstrate that intramuscular FES can enable monkeys with temporarily paralyzed hands to move their fingers and wrist across a functional range of motion, spanning an average 88.6 degrees at the metacarpophalangeal joint flexion and 71.3 degrees of wrist flexion, and intramuscular FES can control both joints simultaneously in a real-time task. Additionally, we demonstrate a monkey using an intracortical BMI to control the wrist and finger flexion in a virtual hand, both before and after the hand is temporarily paralyzed, even achieving success rates and acquisition times equivalent to able-bodied control with BMI control after temporary paralysis in two sessions. Together, this outlines a method using an artificial brain-to-body interface that could restore continuous wrist and finger movements after spinal cord injury.
脑机接口(BMI)控制的功能性电刺激(FES)是恢复颈脊髓损伤患者手部运动的一种很有前景的治疗方法。最近的皮层内 BMI 在解码用户意图方面取得了前所未有的成功,但通过功能性电刺激恢复的手部运动在很大程度上仅限于预定的抓握动作。恢复灵巧的手部动作需要持续控制手部许多生物力学相关的自由度,如手腕和手指的弯曲,这将构成这些动作的基础。在此,我们研究了恢复手腕和手指同时屈曲的能力,这将有助于以可控的手部姿势进行抓取,并在抓取物体后协助操作。我们证明,肌肉内固定电子促进电刺激可以使双手暂时瘫痪的猴子在功能性运动范围内移动手指和手腕,掌指关节平均弯曲 88.6 度,腕关节平均弯曲 71.3 度,而且肌肉内固定电子促进电刺激可以在实时任务中同时控制两个关节。此外,我们还演示了一只猴子使用皮层内 BMI 控制虚拟手的腕关节和手指屈曲,无论是在手暂时瘫痪之前还是之后,甚至在两次暂时瘫痪后使用 BMI 控制的成功率和获得时间都与健全人控制相当。总之,这概述了一种使用人工脑-体接口的方法,可以在脊髓损伤后恢复手腕和手指的连续运动。
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引用次数: 0
Delineating In-Vivo T1-Weighted Intensity Profiles Within the Human Insula Cortex Using 7-Tesla MRI 利用 7 特斯拉核磁共振成像描绘人体岛叶皮层内的活体 T1 加权强度轮廓
Pub Date : 2024-08-12 DOI: 10.1101/2024.08.05.605123
Connor Dalby, Austin Jon Dibble, Joana Carvalheiro, Filippo Queirazza, Michele Sevegnani, Monika Harvey, Michele Svanera, Alessio Fracasso
The integral role of the insula cortex in sensory and cognitive function has been well documented in humans, and fine anatomical details characterising the insula have been extensively investigated ex-vivo in both human and non-human primates. However, in-vivo studies of insula anatomy in humans (in general), and within-insula parcellation (in particular) have been limited. The current study leverages 7 tesla magnetic resonance imaging to delineate T1-weighted intensity profiles within the human cortex, serving as an indirect proxy of myelination. Our analysis revealed two separate clusters of relatively high and low T1-weighted signal intensity across the insula cortex located in three distinct cortical locations within the posterior, anterior, and middle insula. The posterior and anterior cortical locations are characterised by elevated T1-weighted signal intensities, contrasting with lower intensity observed in the middle insular cortical location, compatible with ex-vivo studies. Importantly, the detection of the high T1-weighted anterior cluster is determined by the choice of brain atlas employed to define the insular ROI. We obtain reliable in-vivo within-insula parcellation at the individual and group levels, across two separate cohorts acquired in two separate sites (n1 = 21, Glasgow, UK; n2 = 101, Amsterdam, NL). These results reflect new insights into the insula anatomical structure, in-vivo, while highlighting the use of 7 tesla in neuroimaging. Specifically, the current study also paves the way to study within-insula parcellation at 7 tesla and above, and discusses further implications for individualised medicine approaches.
在人类中,脑岛皮层在感觉和认知功能中扮演着不可或缺的角色,这一点已经得到了充分的证实,而在人类和非人灵长类动物体内,脑岛的精细解剖细节也得到了广泛的研究。然而,对人类脑岛解剖结构(总体而言)和半岛内分割(特别是)的体内研究却很有限。目前的研究利用 7 特斯拉磁共振成像技术来描绘人类皮层内的 T1 加权强度剖面,作为髓鞘化的间接代表。我们的分析显示,在整个岛叶皮层中,有两个相对较高和较低 T1 加权信号强度的独立集群,分别位于岛叶后部、前部和中部的三个不同皮层位置。后部和前部皮层位置的特征是 T1 加权信号强度升高,而在中间岛叶皮层位置观察到的信号强度较低,这与体外研究结果相符。重要的是,前部高 T1 加权群的检测取决于定义岛叶 ROI 时所选择的脑图谱。我们在两个不同地点(n1 = 21,英国格拉斯哥;n2 = 101,荷兰阿姆斯特丹)获得的两个独立队列中,在个体和群体水平上获得了可靠的体内半岛内解析。这些结果反映了对体内岛叶解剖结构的新认识,同时突出了 7 特斯拉在神经成像中的应用。具体而言,目前的研究还为在 7 特斯拉及以上的频率下研究半岛内的配位铺平了道路,并探讨了对个体化医疗方法的进一步影响。
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引用次数: 0
Local Synthesis of Reticulon-1C Lessens the Outgrowth of Injured Axons by Controlling Spastin Activity 网状纤维素-1C 的局部合成通过控制痉挛素的活性减少损伤轴突的生长
Pub Date : 2024-08-12 DOI: 10.1101/2024.08.11.607514
Alejandro Luarte, Javiera Gallardo, Daniela Corvalan, Ankush Chakraborty, Claudio Gouveia-Roque, Francisca Bertin, Carlos Contreras, Juan Pablo Ramirez, Andre Weber, Waldo Acevedo, Werner Zuschratter, Rodrigo Herrera, Ursula Wyneken, Andrea Paula Lima, Tatiana Adasme, Antonia Figueroa, Carolina Gonzalez, Christian Gonzalez-Billault, Ulrich Hengst, Andres Couve
The regenerative potential of developing cortical axons following injury depends on intrinsic mechanisms, such as axon-autonomous protein synthesis, that are still not fully understood. An emerging factor in this regenerative process is the bi-directional interplay between microtubule dynamics and structural proteins of the axonal endoplasmic reticulum. Therefore, we hypothesize that locally synthesized structural proteins of the endoplasmic reticulum may regulate microtubule dynamics and the outgrowth of injured cortical axons. This hypothesis is supported by RNA data-mining, which identified Reticulon-1 as the sole ER-shaping protein consistently present in axonal transcriptomes and found it to be downregulated following cortical axon injury. Using compartmentalized microfluidic chambers, we demonstrate that local knockdown of Reticulon-1 mRNA enhances outgrowth while reducing the distal tubulin levels of injured cortical axons. Additionally, live cell imaging shows injury-induced reductions in microtubule growth rate and length, which are fully restored by axonal Reticulon-1 knockdown. Interestingly, axonal inhibition of the microtubule-severing protein Spastin fully prevents the effects of local Reticulon-1 knockdown on outgrowth and tubulin levels, while not affecting microtubule dynamics. Furthermore, we provide evidence supporting that the Reticulon-1C isoform is locally synthesized in injured axons and associates with Spastin to inhibit its severing activity. Our findings reveal a novel injury-dependent mechanism in which a locally synthesized ER-shaping protein lessens microtubule dynamics and the outgrowth of cortical axons.
发育中的大脑皮层轴突在损伤后的再生潜力取决于内在机制,如轴突自主蛋白质合成,但人们对这一机制的了解仍不全面。这一再生过程中的一个新因素是微管动力学与轴突内质网结构蛋白之间的双向相互作用。因此,我们假设,局部合成的内质网结构蛋白可能会调节微管动力学和受伤皮质轴突的生长。这一假设得到了 RNA 数据挖掘的支持,RNA 数据挖掘发现 Reticulon-1 是唯一持续存在于轴突转录组中的 ER 塑形蛋白,并发现它在大脑皮层轴突损伤后被下调。利用分区微流控芯片,我们证明了局部敲除Reticulon-1 mRNA能增强轴突的生长,同时降低受损皮质轴突的远端微管蛋白水平。此外,活细胞成像显示,损伤诱导的微管生长速度和长度减少,而轴突Reticulon-1基因敲除可完全恢复。有趣的是,轴突抑制微管分裂蛋白 Spastin 完全阻止了局部 Reticulon-1 敲除对外延生长和微管蛋白水平的影响,同时不影响微管动力学。此外,我们还提供证据证明,Reticulon-1C 同工型在损伤轴突中局部合成,并与 Spastin 结合以抑制其切断活性。我们的研究结果揭示了一种新的损伤依赖性机制,在这种机制中,局部合成的ER塑形蛋白会降低微管动力学和大脑皮层轴突的生长。
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引用次数: 0
Neural Sequences Underlying Directed Turning in C. elegans 草履虫定向转弯的神经序列
Pub Date : 2024-08-11 DOI: 10.1101/2024.08.11.607076
Talya S Kramer, Flossie K Wan, Sarah M Pugliese, Adam A Atanas, Alex W Hiser, Jinyue Luo, Eric Bueno, Steven W Flavell
Complex behaviors like navigation rely on sequenced motor outputs that combine to generate effective movement. The brain-wide organization of the circuits that integrate sensory signals to select and execute appropriate motor sequences is not well understood. Here, we characterize the architecture of neural circuits that control C. elegans olfactory navigation. We identify error-correcting turns during navigation and use whole-brain calcium imaging and cell-specific perturbations to determine their neural underpinnings. These turns occur as motor sequences accompanied by neural sequences, in which defined neurons activate in a stereotyped order during each turn. Distinct neurons in this sequence respond to sensory cues, anticipate upcoming turn directions, and drive movement, linking key features of this sensorimotor behavior across time. The neuromodulator tyramine coordinates these sequential brain dynamics. Our results illustrate how neuromodulation can act on a defined neural architecture to generate sequential patterns of activity that link sensory cues to motor actions.
复杂的行为(如导航)依赖于有序的运动输出,这些输出结合在一起才能产生有效的运动。目前对整合感觉信号以选择和执行适当运动序列的全脑电路组织尚不十分清楚。在这里,我们描述了控制秀丽隐杆线虫嗅觉导航的神经回路结构。我们确定了导航过程中的纠错转向,并利用全脑钙成像和细胞特异性扰动来确定其神经基础。这些转弯以运动序列的形式出现,并伴有神经序列,其中确定的神经元在每次转弯时都会以刻板的顺序激活。该序列中的不同神经元会对感觉线索做出反应,预测即将到来的转弯方向,并驱动运动,从而将这种感觉运动行为的关键特征在不同时间内联系起来。神经调节剂酪胺能协调这些连续的大脑动态。我们的研究结果说明了神经调节如何作用于一个确定的神经结构,从而产生将感觉线索与运动行为联系起来的连续活动模式。
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引用次数: 0
AmygdalaGo-BOLT3D: A boundary learning transformer for tracing human amygdala AmygdalaGo-BOLT3D:用于追踪人类杏仁核的边界学习转换器
Pub Date : 2024-08-11 DOI: 10.1101/2024.08.11.607487
Bo Dong, Quan Zhou, Peng Gao, Wei Jintao, Jiale Xiao, Wei Wang, Peipeng Liang, Danhua Lin, Hongjian He, Xi-Nian Zuo
Automated amygdala segmentation is one of the most common tasks in human neuroscience research. However, due to the small volume of the human amygdala, especially in developing brains, the precision and consistency of the segmentation results are often affected by individual differences and inconsistencies in data distribution. To address these challenges, we propose an algorithm for learning boundary contrast of 427 manually traced amygdalae in children and adolescents to generate a transformer, AmygdalaGo-BOLT3D, for automatic segmentation of human amygdala. This method focuses on the boundary to effectively address the issue of false positive recognition and inaccurate edges due to small amygdala volume. Firstly, AmygdalaGo-BOLT3D develops a basic architecture for an adaptive cooperation network with multiple granularities. Secondly, AmygdalaGo-BOLT3D builds the self-attention-based consistency module to address generalizability problems arising from individual differences and inconsistent data distributions. Third, AmygdalaGo-BOLT3D adapts the original sample-mask model for the amygdala scene, which consists of three parts, namely a lightweight volumetric feature encoder, a 3D cue encoder, and a volume mask decoder, to improve the generalized segmentation of the model. Finally, AmygdalaGo-BOLT3D implements a boundary contrastive learning framework that utilizes the interaction mechanism between a prior cue and the embedded magnetic resonance images to achieve effective integration between the two. Experimental results demonstrate that predictions of the overall structure and boundaries of the human amygdala exhibit highly improved precision and help maintain stability in multiple age groups and imaging centers. This verifies the stability and generalization of the algorithm designed for multiple tasks. AmygdalaGo-BOLT3D has been deployed for the community (GITHUB_LINK) to provide an open science foundation for its applications in population neuroscience.
杏仁核自动分割是人类神经科学研究中最常见的任务之一。然而,由于人类杏仁核体积小,尤其是发育中的大脑,分割结果的精确性和一致性往往受到个体差异和数据分布不一致的影响。为了应对这些挑战,我们提出了一种算法,用于学习 427 个人工追踪的儿童和青少年杏仁核的边界对比,从而生成一个转换器 AmygdalaGo-BOLT3D,用于人类杏仁核的自动分割。该方法以边界为重点,有效解决了杏仁核体积小导致的假阳性识别和边缘不准确的问题。首先,AmygdalaGo-BOLT3D 开发了多粒度自适应合作网络的基本架构。其次,AmygdalaGo-BOLT3D 建立了基于自我注意的一致性模块,以解决因个体差异和数据分布不一致而产生的普适性问题。第三,AmygdalaGo-BOLT3D 对原有的杏仁核场景样本掩码模型进行了调整,该模型由三部分组成,即轻量级体积特征编码器、三维线索编码器和体积掩码解码器,以提高模型的泛化分割能力。最后,AmygdalaGo-BOLT3D 实现了边界对比学习框架,利用先验线索与嵌入式磁共振图像之间的交互机制,实现两者之间的有效整合。实验结果表明,对人类杏仁核整体结构和边界的预测显示出高度的精确性,并有助于在多个年龄组和成像中心保持稳定。这验证了针对多种任务设计的算法的稳定性和通用性。AmygdalaGo-BOLT3D已经部署到社区(GITHUB/_LINK),为其在群体神经科学中的应用提供了一个开放的科学基础。
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引用次数: 0
Formation of brain-wide neural geometry during visual item recognition in monkeys 猴子在视觉项目识别过程中形成的全脑神经几何图形
Pub Date : 2024-08-11 DOI: 10.1101/2024.08.05.604527
He Chen, Jun Kunimatsu, Tomomichi Oya, Yuri Imaizumi, Yukiko Hori, Masayuki Matsumoto, Yasuhiro Tsubo, Okihide Hikosaka, Takafumi Minamimoto, Yuji Naya, Hiroshi Yamada
Neural dynamics reflect canonical computations that relay and transform information in the brain. Previous studies have identified the neural population dynamics in many individual brain regions as a trajectory geometry in a low-dimensional neural space. However, whether these populations share particular geometric patterns across brain-wide neural populations remains unclear. Here, by mapping neural dynamics widely across temporal/frontal/limbic regions in the cortical and subcortical structures of monkeys, we show that 10 neural populations, including 2,500 neurons, propagate visual item information in a stochastic manner. We found that the visual inputs predominantly evoked rotational dynamics in the higher-order visual area, the TE and its downstream striatum tail, while curvy/straight dynamics appeared more frequently downstream in the orbitofrontal/hippocampal network. These geometric changes were not deterministic but rather stochastic according to their respective emergence rates. These results indicated that visual information propagates as a heterogeneous mixture of stochastic neural population signals in the brain.
神经动态反映了大脑中传递和转换信息的典型计算。以往的研究已将许多单个脑区的神经群动态确定为低维神经空间中的轨迹几何。然而,这些神经群是否在整个大脑神经群中共享特定的几何模式仍不清楚。在这里,我们通过广泛绘制猴子皮层和皮层下结构中颞叶/额叶/边缘区域的神经动态图,表明包括 2,500 个神经元在内的 10 个神经群以随机方式传播视觉项目信息。我们发现,视觉输入主要在高阶视觉区、TE 及其下游纹状体尾部唤起旋转动态,而在下游的眶额叶/海马网络中则更频繁地出现曲线/直线动态。这些几何变化并不是确定性的,而是根据各自的出现率随机发生的。这些结果表明,视觉信息是作为随机神经群信号的异质混合物在大脑中传播的。
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引用次数: 0
Neural Mechanism Underlying Successful Classification of Amnestic Mild Cognitive Impairment Using Multi-Sensory-Evoked Potentials 利用多传感器诱发电位成功划分失忆性轻度认知障碍的神经机制
Pub Date : 2024-08-11 DOI: 10.1101/2024.08.10.607449
Lei Zhang, Malcom Binns, Ricky Chow, Rahel Rabi, Nicole D. Anderson, Jing Lu, Morris Freedman, Claude Alain
Introduction: The diagnosis, prognosis, and management of amnestic mild cognitive impairment (aMCI) remains challenging. Early detection of aMCI is crucial for timely interventions. Method: This study combines scalp recordings of auditory, visual, and somatosensory stimuli with a flexible and interpretable support vector machine classification pipeline to differentiate individuals diagnosed with aMCI from healthy controls. Results: Event-related potentials (ERPs) and functional connectivity (FC) matrices from each modality successfully predicted aMCI. We got optimal classification accuracy (96.1%), sensitivity (97.7%) and specificity (94.3%) when combining information from all sensory conditions than when using information from a single modality. Reduced ERP amplitude, higher FC in frontal region which predicted worse cognitive performance, and lower FC in posterior regions from delta to alpha frequency in aMCI contributed to classification.Conclusions: The results highlight the clinical potential of sensory-evoked potentials in detecting aMCI, with optimal classification using both amplitude and oscillatory-based FC measures from multiple modalities.
简介失忆性轻度认知障碍(aMCI)的诊断、预后和管理仍然具有挑战性。早期发现轻度认知障碍对及时干预至关重要。研究方法本研究将听觉、视觉和体感刺激的头皮记录与灵活、可解释的支持向量机分类管道相结合,以区分被诊断为 aMCI 的个体和健康对照组。研究结果来自每种模式的事件相关电位(ERPs)和功能连接矩阵(FC)都能成功预测急性脑梗塞。与使用单一模式的信息相比,结合所有感官条件的信息可获得最佳的分类准确率(96.1%)、灵敏度(97.7%)和特异性(94.3%)。在 aMCI 中,ERP 振幅减小、额叶区域的 FC 较高,这预示着认知表现较差,而后部区域从 delta 到 alpha 频率的 FC 较低,这都有助于分类:这些结果凸显了感觉诱发电位在检测 aMCI 方面的临床潜力,使用多种模式的振幅和基于振荡的 FC 测量可进行最佳分类。
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引用次数: 0
Relative phase of distributed oscillatory dynamics implements a working memory in a simple brain 分布式振荡动力学的相对相位在简单大脑中实现了工作记忆
Pub Date : 2024-08-11 DOI: 10.1101/2024.08.11.607402
Raymond L Dunn, Caitriona Costello, Jackson M Borchardt, Daniel Yutaka Sprague, Grace C Chiu, Julia M Miller, Noelle L'Etoile, Saul Kato
We report the existence of a working memory system in the nematode C. elegans that is employed for deferred action in a sensory-guided decision-making process. We find that the turn direction of discrete reorientations during navigation is under sensory-guided control and relies on a working memory that can persist over an intervening behavioral sequence. This memory system is implemented by the phasic interaction of two distributed oscillatory dynamical components. The interaction of oscillatory neural ensembles may be a conserved primitive of cognition across the animal kingdom.
我们报告了线虫中工作记忆系统的存在,该系统在感官引导的决策过程中被用于延迟行动。我们发现,在导航过程中,离散方向调整的转向是在感觉引导控制下进行的,并且依赖于一种工作记忆,这种工作记忆可以在行为序列中持续存在。这种记忆系统是通过两个分布式振荡动态成分的相位相互作用实现的。振荡神经组合的相互作用可能是动物界中一种保守的原始认知方式。
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引用次数: 0
Spatial transcriptomic data reveals pure cell types via the mosaic hypothesis 空间转录组数据通过镶嵌假说揭示纯细胞类型
Pub Date : 2024-08-10 DOI: 10.1101/2024.08.09.607193
Yiliu Wang, Christof Koch, Uygar Sümbül
Neurons display remarkable diversity in their anatomical, molecular, and physiological properties. Although observed stereotypy in subsets of neurons is a pillar of neuroscience, clustering in high-dimensional feature spaces, such as those defined by single cell RNA-seq data, is often inconclusive and cells seemingly occupy continuous, rather than discrete, regions. In the retina, a layered structure, neurons of the same discrete type avoid spatial proximity with each other. While this principle, which is independent of clustering in feature space, has been a gold standard for retinal cell types, its applicability to the cortex has been only sparsely explored. Here, we provide evidence for such a mosaic hypothesis by developing a statistical point process analysis framework for spatial transcriptomic data. We demonstrate spatial avoidance across many excitatory and inhibitory neuronal types. Spatial avoidance disappears when cell types are merged, potentially offering a gold standard metric for evaluating the purity of putative cell types.
神经元在解剖、分子和生理特性方面表现出显著的多样性。虽然神经元子集的刻板印象是神经科学的支柱,但在高维特征空间(如单细胞 RNA-seq 数据所定义的空间)中进行聚类往往没有定论,细胞似乎占据连续而非离散的区域。在视网膜这一分层结构中,同一离散类型的神经元避免在空间上相互靠近。这一原则与特征空间中的聚类无关,一直是视网膜细胞类型的黄金标准,但其在大脑皮层中的适用性却鲜有探索。在这里,我们通过开发空间转录组数据的统计点过程分析框架,为这种镶嵌假说提供了证据。我们证明了许多兴奋性和抑制性神经元类型都存在空间回避现象。当细胞类型合并时,空间回避现象就会消失,这有可能为评估假定细胞类型的纯度提供一个金标准指标。
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引用次数: 0
期刊
bioRxiv - Neuroscience
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