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Acetylcholine facilitates localized synaptic potentiation and location specific feature binding 乙酰胆碱促进局部突触增强和位置特异性特征结合
3区 医学 Q2 Neuroscience Pub Date : 2023-11-10 DOI: 10.3389/fncir.2023.1239096
Yihao Yang, Victoria Booth, Michal Zochowski
Forebrain acetylcholine (ACh) signaling has been shown to drive attention and learning. Recent experimental evidence of spatially and temporally constrained cholinergic signaling has sparked interest to investigate how it facilitates stimulus-induced learning. We use biophysical excitatory-inhibitory (E-I) multi-module neural network models to show that external stimuli and ACh signaling can mediate spatially constrained synaptic potentiation patterns. The effects of ACh on neural excitability are simulated by varying the conductance of a muscarinic receptor-regulated hyperpolarizing slow K+ current (m-current). Each network module consists of an E-I network with local excitatory connectivity and global inhibitory connectivity. The modules are interconnected with plastic excitatory synaptic connections, that change via a spike-timing-dependent plasticity (STDP) rule. Our results indicate that spatially constrained ACh release influences the information flow represented by network dynamics resulting in selective reorganization of inter-module interactions. Moreover the information flow depends on the level of synchrony in the network. For highly synchronous networks, the more excitable module leads firing in the less excitable one resulting in strengthening of the outgoing connections from the former and weakening of its incoming synapses. For networks with more noisy firing patterns, activity in high ACh regions is prone to induce feedback firing of synchronous volleys and thus strengthening of the incoming synapses to the more excitable region and weakening of outgoing synapses. Overall, these results suggest that spatially and directionally specific plasticity patterns, as are presumed necessary for feature binding, can be mediated by spatially constrained ACh release.
前脑乙酰胆碱(ACh)信号传导已被证明可以驱动注意力和学习。最近的实验证据表明,空间和时间限制胆碱能信号引发了研究它如何促进刺激诱导学习的兴趣。我们使用生物物理兴奋-抑制(E-I)多模块神经网络模型来证明外部刺激和乙酰胆碱信号可以介导空间受限的突触增强模式。通过改变毒蕈碱受体调节的超极化慢K+电流(m电流)的电导来模拟乙酰胆碱对神经兴奋性的影响。每个网络模块由一个具有局部兴奋性连接和全局抑制性连接的E-I网络组成。这些模块与可塑性兴奋性突触连接相互连接,这种连接通过峰值时间依赖的可塑性(STDP)规则变化。我们的研究结果表明,空间约束的ACh释放影响以网络动力学为代表的信息流,导致模块间相互作用的选择性重组。此外,信息流取决于网络中的同步水平。对于高度同步的神经网络,更容易兴奋的模块会引发不太容易兴奋的模块,导致前者的外向连接加强,而其传入突触减弱。对于具有更嘈杂的放电模式的网络,高乙酰氨基酚区域的活动容易诱导同步齐射的反馈放电,从而加强传入突触到更兴奋的区域,减弱传出突触。总的来说,这些结果表明空间和方向特异性的可塑性模式,作为特征结合的必要条件,可以通过空间约束的乙酰胆碱释放介导。
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引用次数: 0
Editorial: GABAergic circuits in health and disease. 编辑:gaba能回路在健康和疾病。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1322193
Lisa Topolnik, Graziella Di Cristo, Elsa Rossignol
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引用次数: 0
The flow of axonal information among hippocampal sub-regions 2: patterned stimulation sharpens routing of information transmission 海马亚区之间的轴突信息流 2:模式化刺激使信息传输路线更加清晰
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-10-20 DOI: 10.3389/fncir.2023.1272925
Samuel Brandon Lassers, Yash S. Vakilna, William C. Tang, Gregory J. Brewer

The sub-regions of the hippocampal formation are essential for episodic learning and memory formation, yet the spike dynamics of each region contributing to this function are poorly understood, in part because of a lack of access to the inter-regional communicating axons. Here, we reconstructed hippocampal networks confined to four subcompartments in 2D cultures on a multi-electrode array that monitors individual communicating axons. In our novel device, somal, and axonal activity was measured simultaneously with the ability to ascertain the direction and speed of information transmission. Each sub-region and inter-regional axons had unique power-law spiking dynamics, indicating differences in computational functions, with abundant axonal feedback. After stimulation, spiking, and burst rates decreased in all sub-regions, spikes per burst generally decreased, intraburst spike rates increased, and burst duration decreased, which were specific for each sub-region. These changes in spiking dynamics post-stimulation were found to occupy a narrow range, consistent with the maintenance of the network at a critical state. Functional connections between the sub-region neurons and communicating axons in our device revealed homeostatic network routing strategies post-stimulation in which spontaneous feedback activity was selectively decreased and balanced by decreased feed-forward activity. Post-stimulation, the number of functional connections per array decreased, but the reliability of those connections increased. The networks maintained a balance in spiking and bursting dynamics in response to stimulation and sharpened network routing. These plastic characteristics of the network revealed the dynamic architecture of hippocampal computations in response to stimulation by selective routing on a spatiotemporal scale in single axons.

海马形成的各个亚区对情节性学习和记忆的形成至关重要,但人们对每个亚区促进这一功能的尖峰动态却知之甚少,部分原因是缺乏对区域间交流轴突的访问。在这里,我们通过多电极阵列监测单个交流轴突,在二维培养物中重建了局限于四个亚区的海马网络。在我们的新型装置中,体细胞和轴突活动被同时测量,并能确定信息传输的方向和速度。每个子区域和区域间轴突都有独特的幂律尖峰动态,表明计算功能存在差异,轴突反馈也很丰富。刺激后,所有亚区域的尖峰和爆发率均下降,每次爆发的尖峰数普遍减少,爆发内尖峰率增加,爆发持续时间缩短,这在每个亚区域都有特定的表现。研究发现,这些刺激后尖峰动态变化的范围很窄,与网络维持在临界状态一致。我们装置中的子区域神经元和通信轴突之间的功能连接显示了刺激后的平衡网络路由策略,其中自发反馈活动被选择性地减少,并被减少的前馈活动所平衡。刺激后,每个阵列的功能连接数量减少,但这些连接的可靠性却增加了。网络对刺激的反应保持了尖峰和爆发动态的平衡,并使网络路由更加清晰。网络的这些可塑性特征揭示了海马计算的动态结构,它通过单轴突在时空尺度上的选择性路由来响应刺激。
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引用次数: 0
GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential. GABA能信号在酒精使用障碍和戒断中的作用:病理学意义和治疗潜力。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-10-20 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1218737
Ravinder Naik Dharavath, Celeste Pina-Leblanc, Victor M Tang, Matthew E Sloan, Yuliya S Nikolova, Peter Pangarov, Anthony C Ruocco, Kevin Shield, Daphne Voineskos, Daniel M Blumberger, Isabelle Boileau, Nikki Bozinoff, Philip Gerretsen, Erica Vieira, Osnat C Melamed, Etienne Sibille, Lena C Quilty, Thomas D Prevot

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

酒精是使用最广泛的物质之一。酒精使用占全球疾病负担的5.1%,大大增加了社会和经济成本,每年导致全球约300万人死亡。酒精使用障碍(AUD)包括对健康产生短期或长期影响的各种饮酒行为模式。乙醇是酒精饮料中的主要精神活性分子,它直接影响GABA能系统,导致GABA能失调,这种失调因饮酒强度和持续时间而异。已经开发了少量针对GABA能系统的干预措施,但未来还有很有希望的治疗途径可供探索。这篇综述概述了酒精对GABA能系统的影响,目前针对GABA能的AUD干预措施,以及正在探索的新干预措施,这些干预措施将来可能被纳入AUD治疗的一线疗法。
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引用次数: 0
Autogenous cerebral processes: an invitation to look at the brain from inside out. 自主大脑过程:一种从内到外观察大脑的邀请。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-10-19 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1253609
Pedro E Maldonado, Miguel Concha-Miranda, Miriam Schwalm

While external stimulation can reliably trigger neuronal activity, cerebral processes can operate independently from the environment. In this study, we conceptualize autogenous cerebral processes (ACPs) as intrinsic operations of the brain that exist on multiple scales and can influence or shape stimulus responses, behavior, homeostasis, and the physiological state of an organism. We further propose that the field should consider exploring to what extent perception, arousal, behavior, or movement, as well as other cognitive functions previously investigated mainly regarding their stimulus-response dynamics, are ACP-driven.

虽然外部刺激可以可靠地触发神经元活动,但大脑过程可以独立于环境运行。在这项研究中,我们将自体脑过程(ACPs)概念化为大脑的内在操作,存在于多个尺度上,可以影响或塑造刺激反应、行为、稳态和生物体的生理状态。我们进一步提出,该领域应考虑探索感知、唤醒、行为或运动,以及之前主要针对其刺激反应动力学研究的其他认知功能,在多大程度上是ACP驱动的。
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引用次数: 0
Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica. 通过神经递质和神经调节剂与宿主共生体交流的潜力在非整倍体动物,海洋海绵昆士兰两栖动物中。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-09-29 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1250694
Xueyan Xiang, Arturo A Vilar Gomez, Simone P Blomberg, Huifang Yuan, Bernard M Degnan, Sandie M Degnan

Interkingdom signalling within a holobiont allows host and symbionts to communicate and to regulate each other's physiological and developmental states. Here we show that a suite of signalling molecules that function as neurotransmitters and neuromodulators in most animals with nervous systems, specifically dopamine and trace amines, are produced exclusively by the bacterial symbionts of the demosponge Amphimedon queenslandica. Although sponges do not possess a nervous system, A. queenslandica expresses rhodopsin class G-protein-coupled receptors that are structurally similar to dopamine and trace amine receptors. When sponge larvae, which express these receptors, are exposed to agonists and antagonists of bilaterian dopamine and trace amine receptors, we observe marked changes in larval phototactic swimming behaviour, consistent with the sponge being competent to recognise and respond to symbiont-derived trace amine signals. These results indicate that monoamines synthesised by bacterial symbionts may be able to influence the physiology of the host sponge.

全生物体内的界间信号允许宿主和共生体交流并调节彼此的生理和发育状态。在这里,我们发现,在大多数有神经系统的动物中,一系列信号分子,特别是多巴胺和微量胺,作为神经递质和神经调节剂,完全由昆斯兰双足虫的细菌共生体产生。尽管海绵不具有神经系统,但昆士兰a.queenslandica表达与多巴胺和微量胺受体结构相似的视紫红质类G蛋白偶联受体。当表达这些受体的海绵幼虫暴露于双侧多巴胺和微量胺受体的激动剂和拮抗剂时,我们观察到幼虫的趋光游泳行为发生了显著变化,这与海绵能够识别和响应共生体衍生的微量胺信号相一致。这些结果表明,由细菌共生体合成的单胺可能能够影响宿主海绵的生理学。
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引用次数: 0
Echinoderm radial glia in adult cell renewal, indeterminate growth, and regeneration. 棘皮放射状胶质细胞在成体细胞更新、不确定生长和再生中的作用。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-29 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1258370
Vladimir Mashanov, Soji Ademiluyi, Denis Jacob Machado, Robert Reid, Daniel Janies

Echinoderms are a phylum of marine deterostomes with a range of interesting biological features. One remarkable ability is their impressive capacity to regenerate most of their adult tissues, including the central nervous system (CNS). The research community has accumulated data that demonstrates that, in spite of the pentaradial adult body plan, echinoderms share deep similarities with their bilateral sister taxa such as hemichordates and chordates. Some of the new data reveal the complexity of the nervous system in echinoderms. In terms of the cellular architecture, one of the traits that is shared between the CNS of echinoderms and chordates is the presence of radial glia. In chordates, these cells act as the main progenitor population in CNS development. In mammals, radial glia are spent in embryogenesis and are no longer present in adults, being replaced with other neural cell types. In non-mammalian chordates, they are still detected in the mature CNS along with other types of glia. In echinoderms, radial glia also persist into the adulthood, but unlike in chordates, it is the only known glial cell type that is present in the fully developed CNS. The echinoderm radial glia is a multifunctional cell type. Radial glia forms the supporting scaffold of the neuroepithelium, exhibits secretory activity, clears up dying or damaged cells by phagocytosis, and, most importantly, acts as a major progenitor cell population. The latter function is critical for the outstanding developmental plasticity of the adult echinoderm CNS, including physiological cell turnover, indeterminate growth, and a remarkable capacity to regenerate major parts following autotomy or traumatic injury. In this review we summarize the current knowledge on the organization and function of the echinoderm radial glia, with a focus on the role of this cell type in adult neurogenesis.

棘皮动物是一个具有一系列有趣生物学特征的海洋动物门。一个显著的能力是它们令人印象深刻的再生大部分成年组织的能力,包括中枢神经系统(CNS)。研究界积累的数据表明,尽管棘皮动物的成体计划是五径形的,但它们与半脊索动物和脊索动物等双边姐妹类群有着深刻的相似之处。一些新数据揭示了棘皮动物神经系统的复杂性。就细胞结构而言,棘皮动物和脊索动物的中枢神经系统共有的特征之一是存在放射状胶质细胞。在脊索动物中,这些细胞是中枢神经系统发育的主要祖细胞群体。在哺乳动物中,放射状胶质细胞用于胚胎发生,在成年后不再存在,取而代之的是其他类型的神经细胞。在非哺乳动物脊索动物中,它们仍然与其他类型的神经胶质一起在成熟的中枢神经系统中被检测到。在棘皮动物中,放射状胶质细胞也会持续到成年,但与脊索动物不同,它是唯一已知的存在于完全发育的中枢神经系统中的胶质细胞类型。棘皮动物放射状胶质细胞是一种多功能的细胞类型。放射状胶质细胞形成神经上皮的支撑支架,表现出分泌活性,通过吞噬作用清除垂死或受损的细胞,最重要的是,作为主要的祖细胞群体。后一种功能对于成年棘皮动物中枢神经系统突出的发育可塑性至关重要,包括生理细胞更新、不确定的生长以及在自残或创伤后再生主要部分的显著能力。在这篇综述中,我们总结了棘皮动物桡神经胶质的组织和功能的最新知识,重点是这种细胞类型在成人神经发生中的作用。
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引用次数: 0
Local and long-range GABAergic circuits in hippocampal area CA1 and their link to Alzheimer's disease. 海马CA1区的局部和长程GABA能回路及其与阿尔茨海默病的关系。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-09-29 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1223891
Melissa Hernández-Frausto, Olesia M Bilash, Arjun V Masurkar, Jayeeta Basu

GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input-output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer's disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.

GABA能抑制性神经元是大脑中抑制作用的主要来源。传统上,它们在维持兴奋-抑制平衡方面的作用一直被强调。除了稳态功能外,最近的电路映射和功能操作研究揭示了GABA能电路在时空尺度上动态倾斜兴奋-抑制耦合中发挥的广泛特定作用。这些范围从隔室和输入特定信号的门控、增益调制、形成输入输出函数和突触可塑性,到产生信噪比、定义积分和速率码的时间窗口,以及组织神经组装和协调区域间同步。因此,GABA能电路有助于控制单个神经元的计算和行为连接的网络活动。GABA能回路对感觉和记忆信息处理的活动依赖性调节对于海马中情景记忆的形成和维持至关重要。在这里,我们概述了调节海马CA1主要输出区兴奋抑制和去抑制动力学的局部和长程GABA能回路,这对情景记忆至关重要。具体而言,我们将最近关于GABA能神经元分子标记物、电生理特性和突触布线的研究结果与它们在电路水平上的功能联系起来。最后,鉴于CA1区在阿尔茨海默病的早期阶段特别受损,我们强调这些GABA能回路如何参与病理生理学。
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引用次数: 0
Corticospinal excitability after 5-day Dry Immersion in women. 女性干浸泡5天后的皮质脊髓兴奋性。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-09-22 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1163346
Inna Nosikova, Alexandra Riabova, Vladimir Kitov, Elena Tomilovskaya

In light of the development of manned astronautics and the increasing participation of women in space flights, the question of female body adaptation to microgravity conditions becomes relevant. Currently, one of the important directions in this issue is to study the effects of support withdrawal as a factor of weightlessness on the human sensorimotor system. Dry Immersion is one of the well-known ground-based models, which adequately reproduces the main physiological effects of space flight. The aim of this study was to evaluate the changes in motor evoked potentials of the lower leg gravity-dependent muscles in women after a 5-day Dry Immersion. We analyzed evoked responses to transcranial and trans-spinal magnetic stimulation. In this method, areas of interest (the motor cortex and lumbosacral thickening of the spinal cord) are stimulated with an electromagnetic stimulus. The experiment was conducted with the participation of 16 healthy female volunteers with a natural menstrual cycle. The thresholds, amplitudes, and latencies of motor potentials evoked by magnetic stimulation were assessed. We showed that 5-day exposure to support withdrawal leads to a decrease in motor-evoked potential thresholds and central motor conduction time, although changes in motor response amplitudes were ambiguous. The data obtained correspond to the results of previous research on Dry Immersion effects on the sensorimotor system in men.

鉴于载人航天技术的发展和妇女越来越多地参与太空飞行,女性身体适应微重力条件的问题变得重要起来。目前,这一问题的一个重要方向是研究支持撤回作为失重因素对人类感觉运动系统的影响。干式浸没是著名的地面模型之一,它充分再现了太空飞行的主要生理效应。本研究的目的是评估女性在干浸泡5天后小腿重力依赖性肌肉的运动诱发电位的变化。我们分析了经颅和经脊髓磁刺激的诱发反应。在这种方法中,用电磁刺激刺激感兴趣的区域(脊髓的运动皮层和腰骶部增厚)。该实验由16名自然月经周期的健康女性志愿者参与。评估磁刺激诱发的运动电位的阈值、振幅和潜伏期。我们发现,尽管运动反应幅度的变化不明确,但5天的支持退出暴露会导致运动诱发电位阈值和中枢运动传导时间的降低。所获得的数据与先前关于干浸泡对男性感觉运动系统影响的研究结果一致。
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引用次数: 0
Interneuron odyssey: molecular mechanisms of tangential migration. 中间神经元奥德赛:切向迁移的分子机制。
IF 3.5 3区 医学 Q2 Neuroscience Pub Date : 2023-09-14 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1256455
Ikram Toudji, Asmaa Toumi, Émile Chamberland, Elsa Rossignol

Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.

皮质GABA能中间神经元是神经网络的重要组成部分。它们提供局部和长期抑制,并帮助协调参与各种大脑功能的网络活动,包括信号处理、学习、记忆和适应反应。因此,皮质GABA能中间神经元迁移的破坏会导致神经网络组织和功能的严重缺陷,并导致各种神经发育和神经精神障碍,包括癫痫、智力残疾、自闭症谱系障碍和精神分裂症。因此,阐明支配中间神经元迁移的具体机制对于阐明一些潜在的疾病机制至关重要。注定要分布在皮层的GABA能中间神经元来自位于神经节隆起和视前区的多能腹侧祖细胞。有丝分裂后的中间神经元离开其在腹侧前脑的起源地,并利用确定的迁移流向背侧迁移,到达皮层板,它们通过径向迁移进入皮层板,然后分散以最终的层流分配。在迁移过程中,皮层中间神经元通过肌动蛋白和微管细胞骨架的动态重塑不断改变其形态,因为它们检测并整合由分布在迁移路线上的神经元和非神经元来源产生的细胞外引导线索。这些过程确保GABA能中间神经元在皮层区域和椎板中的适当分布,支持充分的网络连接和大脑功能的发展。这篇简短的综述总结了控制皮层GABA能中间神经元迁移的细胞和分子机制的最新知识,重点是切向迁移,并探讨了基于细胞的中间神经元祖细胞移植治疗神经发育障碍和癫痫的潜在途径。
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