Neural interface with a silicon neural probe in the advancement of microtechnology

In this paper we describe the status of a silicon-based microelectrode for neural recording and an advanced neural interface. We have developed a silicon neural probe, using a combination of plasma and wet etching techniques. This process enables the probe thickness to be controlled precisely. To enhance the CMOS compatibility in the fabrication process, we investigated the feasibility of the site material of the doped polycrystalline silicon with small grains of around 50 nm in size. This silicon electrode demonstrated a favorable performance with respect to impedance spectra, surface topography and acute neural recording. These results showed that the silicon neural probe can be used as an advanced microelectrode for neurological applications.     

Characterization of a novel transgenic mouse line expressing Cre recombinase under the control of the Cdx2 neural specific enhancer

Several genetically modified mouse models have been generated in order to drive expression of the Cre recombinase in the neuroectoderm. However, none of them specifically targets the posterior neural plate during neurulation. To fill this gap, we have generated a new transgenic mouse line in which Cre expression is controlled by a neural specific enhancer (NSE) from the Caudal‐related homeobox 2 (Cdx2) locus. Analyses of Cre activity via breeding with R26R‐YFP reporter mice have indicated that the Cdx2NSE‐Cre mouse line allows for recombination of LoxP sites in most cells of the posterior neural plate as soon as from the head fold stage. Detailed examination of double‐transgenic embryos has revealed that this novel Cre‐driver line allows targeting the entire posterior neural tube with an anterior limit in the caudal hindbrain. Of note, the Cdx2NSE regulatory sequences direct Cre expression along the whole dorso‐ventral axis (including pre‐migratory neural crest cells) and, accordingly, YFP fluorescence has been also observed in multiple non‐cranial neural crest derivatives of double‐transgenic embryos. Therefore, we believe that the Cdx2NSE‐Cre mouse line represents an important novel genetic tool for the study of early events occurring in the caudal neuroectoderm during the formation of both the central and the peripheral nervous systems. genesis 51:777–784. © 2013 Wiley Periodicals, Inc.     

Model of autism: increased ratio of excitation/inhibition in key neural systems

Autism is a severe neurobehavioral syndrome, arising largely as an inherited disorder, which can arise from several diseases. Despite recent advances in identifying some genes that can cause autism, its underlying neurological mechanisms are uncertain. Autism is best conceptualized by considering the neural systems that may be defective in autistic individuals. Recent advances in understanding neural systems that process sensory information, various types of memories and social and emotional behaviors are reviewed and compared with known abnormalities in autism. Then, specific genetic abnormalities that are linked with autism are examined. Synthesis of this information leads to a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems. The model further postulates that the increased ratio of excitation/inhibition can be caused by combinatorial effects of genetic and environmental variables that impinge upon a given neural system. Furthermore, the model suggests potential therapeutic interventions.     

多通道神经信号分析方法及其应用

在神经科学研究中,多通道记录方法被普遍应用在对神经元群体活动特性的研究中.通过分析多个神经元的活动,可以了解神经系统协同编码外界信息的规则以及大脑实现各项功能的机制.为了挖掘出多通道神经信号中携带的信息及其潜在的相关性,需要合适的计算方法辅助对神经元放电活动进行解码.本文回顾了多通道神经信号分析中的一些常见方法,以及它...     

小胶质细胞在脑中的生理功能

小胶质细胞是脑中的巨噬细胞,也是脑实质中唯一的一种免疫细胞,因而被看作是中枢神经系统抵御病原入侵的第一道防线。在其他非感染病理状态下,如脑损伤及神经退行性疾病等,小胶质细胞也发挥着保护和毒性损伤的双重作用。相比较其病理功能,人们对小胶质细胞的生理功能长期以来很少关注。然而,近几年关于小胶质细胞生理功能的研究在多个方面都有突破。这些研究结果揭示,小胶质细胞在发育的神经系统中起着调控神经元存活和修饰突触的作用,并且在成熟的健康脑中具有探测和调控神经元活动的功能。将着重对近几年关于小胶质细胞生理功能的相关研究做一综述。     

Neural Population Structures and Consequences for Neural Coding

Researchers studying neural coding have speculated that populations of neurons would more effectively represent the stimulus if the neurons "cooperated:" by interacting through lateral connections, the neurons would process and represent information better than if they functioned independently. We apply our new theory of information processing to determine the fidelity limits of simple population structures to encode stimulus features. We focus on noncooperative populations, which have no lateral connections. We show that they always exhibit positively correlated responses and that as population size increases, they perfectly represent the information conveyed by their inputs regardless of the individual neuron's coding scheme. Cooperative populations, which do have lateral connections, can, depending on the nature of the connections, perform better or worse than their noncooperative counterparts. We further show that common notions of synergy fail to capture the level of cooperation and to reflect the information processing properties of populations.     

Microfabricated nerve–electrode interfaces in neural prosthetics and neural engineering

Neural interfaces and implants are finding more clinical applications and there are rapid technological advances for more efficient and safe design, fabrication and materials to establish high-fidelity neural interfaces. In this review paper, we highlight new developments of the microfabricated electrodes and substrates with regard to the design, materials, fabrication and their clinical applications. There is a noticeable trend towards integration of microfluidic modules on a single neural platform. In addition to the microelectrodes for neural recording and stimulation, microfluidic channels are integrated into a nerve–electrode interface to explore the rich neurochemistry present at the neural interface and exploit it for enhanced electrochemical stimulation and recording of the central and peripheral nervous system.     

Derivation of neural precursor cells from human ES cells at 3% O(2) is efficient, enhances survival and presents no barrier to regional specification and functional differentiation

In vitro stem cell systems traditionally employ oxygen levels that are far removed from the in vivo situation. This study investigates whether an ambient environment containing a physiological oxygen level of 3% (normoxia) enables the generation of neural precursor cells (NPCs) from human embryonic stem cells (hESCs) and whether the resultant NPCs can undergo regional specification and functional maturation. We report robust and efficient neural conversion at 3% O(2), demonstration of tri-lineage potential of resultant NPCs and the subsequent electrophysiological maturation of neurons. We also show that NPCs derived under 3% O(2) can be differentiated long term in the absence of neurotrophins and can be readily specified into both spinal motor neurons and midbrain dopaminergic neurons. Finally, modelling the oxygen stress that occurs during transplantation, we demonstrate that in vitro transfer of NPCs from a 20 to 3% O(2) environment results in significant cell death, while maintenance in 3% O(2) is protective. Together these findings support 3% O(2) as a physiologically relevant system to study stem cell-derived neuronal differentiation and function as well as to model neuronal injury.     

Some recent advances in basic neuroscience research in China

Neuroscience as a distinct discipline or research programme has been a rather recent event in most Chinese universities and in the Chinese Academy of Sciences. However, the last few years have witnessed increased funding and an improved research environment for neuroscience, both of which facilitated an influx of Chinese neuroscientists trained abroad. In this review, we have highlighted some recent research advances made by neuroscientists in China. Based on our own expertise, this review is focused mainly on findings that have contributed to our understanding of the mechanisms underlying brain development, neural plasticity and cognitive processes, and neural degeneration.     

Neural stem cells as therapeutic agents for age-related brain repair

Neurogenesis occurs in two germinal centres of the adult brain and persists with increasing age, although at a reduced level. This observation, that the mature brain can support neurogenesis, has given rise to the hope that neural stem cells could be used to repair the brain by repopulating regions suffering from neuronal loss as a result of injury or disease. The aging brain is vulnerable to mild cognitive impairment, increasing incidence of stroke, and a variety of neurodegenerative diseases. However, most studies to date have focused on the young adult brain, and relatively little information is available about the regulation of neurogenesis in the aged brain or the potential of using neural stem cells to repair the aged brain. This review summarizes the current state of knowledge on neurogenesis in the young adult brain and discusses the information available on age-related changes in neurogenesis. Possible therapeutic strategies using neural stem cells for repair of the aging brain are considered.     

Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

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Optimal Stimulus Coding by Neural Populations Using Rate Codes

We create a framework based on Fisher information for determining the most effective population coding scheme for representing a continuous-valued stimulus attribute over its entire range. Using this scheme, we derive optimal single- and multi-neuron rate codes for homogeneous populations using several statistical models frequently used to describe neural data. We show that each neuron's discharge rate should increase quadratically with the stimulus and that statistically independent neural outputs provides optimal coding. Only cooperative populations can achieve this condition in an informationally effective way.     

条件化恐惧记忆消退的神经振荡机制

恐惧作为个体应对内外界危险因素形成的自我保护机制的一部分,在生物体的生存中发挥着重要作用.但过度的恐惧不仅对个体生存无益,反而易引发创伤后应激障碍、焦虑等精神疾病,严重影响个体生活质量.临床上通常采用基于行为学研究结果的暴露疗法对恐惧相关疾病进行治疗,然而在患者处于治疗环境之外的时候,上述症状经常会复发.因此,解析恐惧记忆相关神经环路内信息处理的神经机制,对于理解这些疾病的发生发展,寻求切实有效的治疗方案至关重要.大量研究表明与恐惧记忆消退相关的脑区主要涉及杏仁核、内侧前额叶和海马.在恐惧消退的过程中,这3个脑区表现出特定的神经振荡模式,而且这些活动也具有同步性,构成了恐惧记忆成功消退的神经基础.未来可利用基于神经神经振荡的无创性脑刺激手段干预恐惧记忆消退的神经环路,以促进恐惧记忆的消退并避免复发,为恐惧相关障碍的临床治疗提供重要的科学依据.     

The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins

Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state.     

miR379–410 cluster miRNAs regulate neurogenesis and neuronal migration by fine‐tuning N‐cadherin

N‐cadherin‐mediated adhesion is essential for maintaining the tissue architecture and stem cell niche in the developing neocortex. N‐cadherin expression level is precisely and dynamically controlled throughout development; however, the underlying regulatory mechanisms remain largely unknown. MicroRNAs (miRNAs) play an important role in the regulation of protein expression and subcellular localisation. In this study, we show that three miRNAs belonging to the miR379–410 cluster regulate N‐cadherin expression levels in neural stem cells and migrating neurons. The overexpression of these three miRNAs in radial glial cells repressed N‐cadherin expression and increased neural stem cell differentiation and neuronal migration. This phenotype was rescued when N‐cadherin was expressed from a miRNA‐insensitive construct. Transient abrogation of the miRNAs reduced stem cell differentiation and increased cell proliferation. The overexpression of these miRNAs specifically in newborn neurons delayed migration into the cortical plate, whereas the knockdown increased migration. Collectively, our results indicate a novel role for miRNAs of the miR379–410 cluster in the fine‐tuning of N‐cadherin expression level and in the regulation of neurogenesis and neuronal migration in the developing neocortex.     

Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior

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Peripheral sensory neurons differentiate from neural precursors derived from human embryonic stem cells

Abstract Neural precursors have been derived from human embryonic stem cells (hESC) using the bone morphogenetic protein antagonist noggin. These neural precursors can be further differentiated to produce neural cells that express central nervous system (CNS) markers. We have recently shown that naïve hESC can be directed to differentiate into peripheral sensory (PS) neuron-like cells and putative neural crest precursors by co-culturing with PA6 stromal cells. In the present study, we examine whether hESC-derived neural precursors (NPC) can differentiate into the peripheral nervous system, as well as CNS cells. As little as 1 week after co-culture with PA6 cells, cells with the molecular characteristics of PS neurons and neural crest are observed in the cultures. With increased time in culture, more PS-like neurons appear, in parallel with a reduction in the neural crest-like cells. These results provide the first evidence that neural precursors derived from hESC have the potential to develop into PS neurons-like as well as CNS-like neuronal cells. About 10% of the cells in NPC-PA6 co-cultures express PS neuron markers after 3 weeks, compared with <1% of hESC cultured on PA6. This enrichment for peripheral neurons makes this an attractive system for generation of peripheral neurons for pathophysiology study and drug development for diseases of the peripheral nervous system such as Familial Dysautonomia and varicella virus infection.     

人工神经网络在发酵工业中的应用

人工神经网络技术具有很强的非线性映射能力,用于系统的非线性建模,具有无可比拟的优势,广泛应用于发酵过程中培养基的优化和系统建模与控制方面,本主要介绍了人工神经网络的基本原理与使用方法,以及BP神经网络在非线性函数逼近的优点,详细介绍了其在发酵培养基优化,连续搅拌反应器神经网络估计,分批发酵及补料分批发酵过程建模与控制优化中的应用实例。