Dopaminergic Modulation of cAMP Drives Nonlinear Plasticity across the Drosophila Mushroom Body Lobes

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Neural Plasticity and Consciousness

We introduce a distinction between cortical dominance andcortical deference, and apply it to various examples ofneural plasticity in which input is rerouted intermodally orintramodally to nonstandard cortical targets. In some cases butnot others, cortical activity `defers' to the nonstandard sourcesof input. We ask why, consider some possible explanations, andpropose a dynamic sensorimotor hypothesis. We believe that thisdistinction is important and worthy of further study, bothphilosophical and empirical, whether or not our hypothesis turnsout to be correct. In particular, the question of how the distinction should be explained is linked to explanatory gapissues for consciousness. Comparative and absolute explanatorygaps should be distinguished: why does neural activity in aparticular area of cortex have this qualitative expressionrather than that, and why does it have any qualitativeexpression at all? We use the dominance/deference distinction toaddress the comparative gaps, both intermodal and intramodal (notthe absolute gap). We do so not by inward scrutiny but rather by expanding our gaze to include relations between brain, body andenvironment.     

Extracellular Matrix in Neural Plasticity and Regeneration

The extracellular matrix (ECM) is a fundamental component of biological tissues. The ECM in the central nervous system (CNS) is unique in both composition and function. Functions such as learning, memory, synaptogenesis, and plasticity are regulated by numerous ECM molecules. The neural ECM acts as a non-specific physical barrier that modulates neuronal plasticity and axon regeneration. There are two specialized types of ECM in the CNS, diffuse perisynaptic ECM and condensed ECM, which selectively surround the perikaryon and initial part of dendritic trees in subtypes of neurons, forming perineuronal nets. This review presents the current knowledge about the role of important neuronal ECM molecules in maintaining the basic functions of a neuron, including electrogenesis and the ability to form neural circuits. The review mainly focuses on the role of ECM components that participate in the control of key events such as cell survival, axonal growth, and synaptic remodeling. Particular attention is drawn to the numerous molecular partners of the main ECM components. These regulatory molecules are integrated into the cell membrane or disposed into the matrix itself in solid or soluble form. The interaction of the main matrix components with molecular partners seems essential in molecular mechanisms controlling neuronal functions. Special attention is paid to the chondroitin sulfate proteoglycan 4, type 1 transmembrane protein, neural-glial antigen 2 (NG2/CSPG4), whose cleaved extracellular domain is such a molecular partner that it not only acts directly on neural and vascular cells, but also exerts its influence indirectly by binding to resident ECM molecules.

     

Vocal Accuracy and Neural Plasticity Following Micromelody-Discrimination Training

Background

Recent behavioral studies report correlational evidence to suggest that non-musicians with good pitch discrimination sing more accurately than those with poorer auditory skills. However, other studies have reported a dissociation between perceptual and vocal production skills. In order to elucidate the relationship between auditory discrimination skills and vocal accuracy, we administered an auditory-discrimination training paradigm to a group of non-musicians to determine whether training-enhanced auditory discrimination would specifically result in improved vocal accuracy.

Methodology/Principal Findings

We utilized micromelodies (i.e., melodies with seven different interval scales, each smaller than a semitone) as the main stimuli for auditory discrimination training and testing, and we used single-note and melodic singing tasks to assess vocal accuracy in two groups of non-musicians (experimental and control). To determine if any training-induced improvements in vocal accuracy would be accompanied by related modulations in cortical activity during singing, the experimental group of non-musicians also performed the singing tasks while undergoing functional magnetic resonance imaging (fMRI). Following training, the experimental group exhibited significant enhancements in micromelody discrimination compared to controls. However, we did not observe a correlated improvement in vocal accuracy during single-note or melodic singing, nor did we detect any training-induced changes in activity within brain regions associated with singing.

Conclusions/Significance

Given the observations from our auditory training regimen, we therefore conclude that perceptual discrimination training alone is not sufficient to improve vocal accuracy in non-musicians, supporting the suggested dissociation between auditory perception and vocal production.     

Analysis of GABAergic and Non-GABAergic Neuron Activity in the Optic Lobes of the Forager and Re-Orienting Worker Honeybee (Apis mellifera L.)

Background

European honeybee (Apis mellifera L.) foragers have a highly developed visual system that is used for navigation. To clarify the neural basis underlying the highly sophisticated visual ability of foragers, we investigated the neural activity pattern of the optic lobes (OLs) in pollen-foragers and re-orienting bees, using the immediate early gene kakusei as a neural activity marker.

Methodology/Principal Findings

We performed double-in situ hybridization of kakusei and Amgad, the honeybee homolog of the GABA synthesizing enzyme GAD, to assess inhibitory neural activity. kakusei-related activity in GABAergic and non-GABAergic neurons was strongly upregulated in the OLs of the foragers and re-orienting bees, suggesting that both types of neurons are involved in visual information processing. GABAergic neuron activity was significantly higher than non-GABAergic neuron activity in a part of the OLs of only the forager, suggesting that unique information processing occurs in the OLs of foragers. In contrast, GABAergic neuron activity in the antennal lobe was significantly lower than that of GABAergic neurons in the OLs in the forager and re-orienting bees, suggesting that kakusei-related visual activity is dominant in the brains of these bees.

Conclusions/Significance

The present study provides the first evidence that GABAergic neurons are highly active in the OL neurons of free-moving honeybees and essential clue to reveal neural basis of the sophisticated visual ability that is equipped in the small and simple brain.     

听觉选择性注意的可塑性及其神经机制研究

本文旨在研究音乐训练是否能增强基于音高和空间位置的听觉选择性注意力,以及音乐训练对听觉可塑性的神经机制.听觉感知实验中,受试者根据音高差异或空间位置差异,选择两个同时播放的数字之一.听觉认知实验在安静和噪声环境中播放频率分辨率不同的复合音,记录受试者听觉脑干频率跟随响应(frequency-following responses,FFRs).本文提出分析FFR的四种方法,即包络相关频率跟随响应(envelope-related frequency-following response,FFRENV)的短时锁相值、瞬时相位差极性图、相位差均值矢量以及时间细节结构相关频率跟随响应(temporal-fine-structure-related frequency-following response,FFRTFS)的幅度谱信噪比.实验结果表明,在完成基于音高的任务时,受过音乐训练的受试者准确率更高、反应时间更短.外界噪声不影响两组人群在基频(fundamental frequency,F0)的神经元锁相能力,但是显著降低了谐波处的神经元锁相能力.受过音乐训练的受试者的神经元在基频处的锁相能力和谐波处抗噪能力均增强,且其FFRTFS幅度谱信噪比与基于音高的行为学准确率呈正相关.因此,受过音乐训练的受试者其音高选择性注意感知能力的提高取决于认知神经能力的增强,经过音乐训练后,F0处FFRENV的锁相能力、谐波处FFRTFS的抗噪和持续锁相能力以及谐波处FFRTFS幅度谱信噪比均明显增强.音乐训练对听觉选择性注意具有显著的可塑性.     

Learning-Induced Synchronization and Plasticity of a Developing Neural Network

Learning-induced synchronization of a neural network at various developing stages is studied by computer simulations using a pulse-coupled neural network model in which the neuronal activity is simulated by a one-dimensional map. Two types of Hebbian plasticity rules are investigated and their differences are compared. For both models, our simulations show a logarithmic increase in the synchronous firing frequency of the network with the culturing time of the neural network. This result is consistent with recent experimental observations. To investigate how to control the synchronization behavior of a neural network after learning, we compare the occurrence of synchronization for four networks with different designed patterns under the influence of an external signal. The effect of such a signal on the network activity highly depends on the number of connections between neurons. We discuss the synaptic plasticity and enhancement effects for a random network after learning at various developing stages.     

Cellular Plasticity Among Axolotl Neural Crest-Derived Pigment Cell Lineages

Many of the factors and mechanisms guiding the migration/differentiation of neural crest cells that give rise to a number of distinguishable cell types, including all dermal and epidermal pigment cells, remain unknown. The axolotl possesses three pigment cell types that differentiate according to specific developmentally programmed sequences and contribute to pigment pattern in the adult. A single lineage of the crest that becomes restricted to one of three pigment cell types gives us the opportunity to examine the existence of a neural crest stem cell population and the potential for transdifferentiation events. Interpretations of experiments involving drug-treated and mutant axolotls implicate cellular plasticity leading to observed phenotypes. We present results from recent in vitro studies designed to identify parameters influencing differentiation events of individual neural crest-derived pigment cell lineages. We demonstrate that the differentiation of xanthophores is enhanced, while that of the melanophores are inhibited in guanosine-supplemented neural crest cell cultures. Data suggest that the increase in one pigment cell population is at the expense of another, indicative of cellular plasticity. Videomicroscopy used in this study agrees with an abundance of correlative evidence supporting the hypothesis of transdifferentiation events among neural crest-derived pigment cell populations. The embryonic neural crest-derived pigment cell system is an ideal model to study differentiation of multipotential stem cells that play critical roles in patterning.     

体外培养的神经元网络可塑性

神经元网络是大脑执行高级认知行为的结构基础,研究证明学习记忆及神经退行性疾病与神经元网络可塑性密切相关。因此,揭示调控和改变神经元网络可塑性的机制对理解神经系统信息交互以及疾病治疗具有重大意义。目前,基于微电极阵列（microelectrode array, MEA）培养的神经元网络是体外探究学习和记忆机制的理想模型,同时针对该模型的研究为预防和治疗神经退行性疾病提供了独特的视角。本文综述了基于MEA采集体外培养神经元网络的放电信号来构建功能网络的相关研究,分别从二维神经元网络和三维脑类器官发育,以及开环和闭环电刺激对神经元网络可塑性影响的角度,总结了体外培养神经元网络可塑性的相关研究,最后对该方向的应用前景进行了展望。     

高级视皮层可塑性:物体和面孔知觉学习综述

复杂刺激的知觉学习是指由训练或经验引起的对物体或者面孔等复杂视觉刺激在知觉上长期稳定的改变,一般认为这反映了大脑高级视皮层的可塑性.对简单刺激知觉学习特性的研究已经揭示了低级视皮层的部分可塑性,但是复杂刺激知觉学习的神经机制目前仍存在争议.本文介绍了知觉学习的理论模型和实验证据,并重点探讨了复杂刺激如物体和面孔知觉学习的特性、神经机制及研究方法.该领域未来需要在复杂刺激知觉学习的持久性、面孔不同属性知觉学习的机制,以及复杂刺激知觉学习的理论模型方面做进一步研究.     

Adventures in Neural Plasticity, Aging, and Neurodegenerative Disorders Aboard the CWC Beagle

This article recounts some of the scientific endeavors of Carl W. Cotman (CWC) during his journeys through the cellular circuitry of the mammalian brain. I have selected for consideration his findings that have been an important impetus for my own research; in several cases our different experiments have provided complementary data to support an hypothesis. Three examples are (i) Carl's studies of the roles of glutamate in synaptic transmission and plasticity in the adult brain and my studies of how glutamate regulates neurite outgrowth and cell survival in brain development; (ii) his and our studies of the mechanisms whereby amyloid -peptide damages and kills neurons; and (iii) Carl's evidence that physical activity regulates neurotrophin levels in the brain and our evidence that dietary restriction has similar effects and is neuroprotective. In case you have not yet realized how I chose a title for this article it is because Carl has a (very distant) connection with Charles Darwin—Darwin sailed on a vessel called the Beagle and Carl has studied beagle dogs, establishing them as a model for understanding the neurobiology of human brain aging.     

Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity

At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant’s nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model’s frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one’s own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop in infancy but also for our understanding of how they may have evolved.     

神经管畸形相关基因的研究进展

神经管畸形是由遗传和环境因素共同作用而导致的一种常见的出生缺陷。遗传因素中包括细胞增殖因子、转录因子及影响叶酸代谢的关键酶的基因。本文着重从动物模型和群体流行病学调查两方面,简述目前研究的热点基因及特定位点的遗传多态性与神经管畸形的关系,从而揭示多因素作用在神经管畸形病因学研究中的意义。 Progress in Researches on Neural Tube Defects Related the Genes QU Mei,LI Zhu Institute of Reproductive and Child Health of Peking University,National Reference Laboratory on Reproductive Health Research Ministry of Health,Beijing 100083,China Abstract:Neural tube defects are common birth defects which are ascribed to the combination of genetic and environmental factors.The genetic factors include cell growth factors,transformation factors and key enzymic genes involved in folate metabolism.This paper reviews the genes as focus of current investigantion and the relationship between the genetic polymorphism on the specific sites and neural tube defects based on animal model and population epidemiological study.It indicats that the multifactors play an important role in the etiology of neural tube defects. Key words：neural tube defects; genetic polymorphism     

Synaptic Plasticity in Neural Networks Needs Homeostasis with a Fast Rate Detector

Hebbian changes of excitatory synapses are driven by and further enhance correlations between pre- and postsynaptic activities. Hence, Hebbian plasticity forms a positive feedback loop that can lead to instability in simulated neural networks. To keep activity at healthy, low levels, plasticity must therefore incorporate homeostatic control mechanisms. We find in numerical simulations of recurrent networks with a realistic triplet-based spike-timing-dependent plasticity rule (triplet STDP) that homeostasis has to detect rate changes on a timescale of seconds to minutes to keep the activity stable. We confirm this result in a generic mean-field formulation of network activity and homeostatic plasticity. Our results strongly suggest the existence of a homeostatic regulatory mechanism that reacts to firing rate changes on the order of seconds to minutes.     

Closely Related Wolbachia Strains within the Pumpkin Arthropod Community and the Potential for Horizontal Transmission via the Plant

Phylogenetic studies have implicated frequent horizontal transmission of Wolbachia among arthropod host lineages. However, the ecological routes for such lateral transfer are poorly known. We surveyed the species of two arthropod communities, one on pumpkin and the other on loofah plants, for Wolbachia, constructed wsp gene phylogenies of those Wolbachia strains found to infect community members, and established ecological links among infected members. Four taxonomically diverse insects in the pumpkin arthropod community contained very closely related Wolbachia wsp sequences (<1.5% divergence by Kimura-2-parameter distances). These insects, namely, the whitefly Bemisia tabaci, the planthopper Nisia nervosa, the flea beetle Phyllotreta sp., and the fleahopper Halticus minutus, were all collected from pumpkin leaves. They were ecologically linked through feeding on the same leaf substrate. Unlike other infected leaf insects, the whitefly population appeared to have a permanent breeding relationship with pumpkin plants, and high and stable, but not fixed, monthly Wolbachia infection rates. Our findings suggest potential roles for the plant in Wolbachia transmission and for whiteflies in being an infection source for other pumpkin leaf-feeding insects.