Sleep in Drosophila is regulated by adult mushroom bodies

Sleep is one of the few major whole-organ phenomena for which no function and no underlying mechanism have been conclusively demonstrated. Sleep could result from global changes in the brain during wakefulness or it could be regulated by specific loci that recruit the rest of the brain into the electrical and metabolic states characteristic of sleep. Here we address this issue by exploiting the genetic tractability of the fruitfly, Drosophila melanogaster, which exhibits the hallmarks of vertebrate sleep. We show that large changes in sleep are achieved by spatial and temporal enhancement of cyclic-AMP-dependent protein kinase (PKA) activity specifically in the adult mushroom bodies of Drosophila. Other manipulations of the mushroom bodies, such as electrical silencing, increasing excitation or ablation, also alter sleep. These results link sleep regulation to an anatomical locus known to be involved in learning and memory.     

Visual place learning in Drosophila melanogaster

The ability of insects to learn and navigate to specific locations in the environment has fascinated naturalists for decades. The impressive navigational abilities of ants, bees, wasps and other insects demonstrate that insects are capable of visual place learning, but little is known about the underlying neural circuits that mediate these behaviours. Drosophila melanogaster (common fruit fly) is a powerful model organism for dissecting the neural circuitry underlying complex behaviours, from sensory perception to learning and memory. Drosophila can identify and remember visual features such as size, colour and contour orientation. However, the extent to which they use vision to recall specific locations remains unclear. Here we describe a visual place learning platform and demonstrate that Drosophila are capable of forming and retaining visual place memories to guide selective navigation. By targeted genetic silencing of small subsets of cells in the Drosophila brain, we show that neurons in the ellipsoid body, but not in the mushroom bodies, are necessary for visual place learning. Together, these studies reveal distinct neuroanatomical substrates for spatial versus non-spatial learning, and establish Drosophila as a powerful model for the study of spatial memories.     

A subset of dopamine neurons signals reward for odour memory in Drosophila

Animals approach stimuli that predict a pleasant outcome. After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour. Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation, the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed. We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals. Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.     

雄激素受体类似物在拟黑多刺蚁脑部的表达和定位

采用免疫组织化学SABC染色方法,对雄激素受体类似物在拟黑多刺蚁的雄蚁与工蚁脑部的表达与分布进行了检测研究.检测结果显示,雄激素受体类似物在拟黑多刺蚁雄蚁与工蚁的蕈形体冠部、柄部、根部以及中央复合体均有分布,并推测该雄激素受体类似物可能对蚂蚁的学习记忆以及求偶进攻等行为有一定影响.     

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.     

A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock

Between 5 and 20% of the adult population in Western countries suffer from insufficient and/or unsatisfying sleep, often associated with certain psychiatric disorders or with certain types of professional activities (for example, shift workers) and travel schedules (for example, jet lag). The benzodiazepines are at present the drug treatment of choice for the management of anxiety and stress-related conditions as well as insomnia. Benzodiazepines are thought to act by potentiating the action of the neurotransmitter gamma-aminobutyric acid (GABA), a widely distributed transmitter in the central nervous system. The circadian system has a key role in the regulation of the sleep-wake cycle, and at least some forms of insomnia may be the result of a disorder of the circadian sleep-wake rhythm. Similarly, at least some forms of depression may also involve disruption of normal circadian rhythmicity. A central pacemaker for the generation of many circadian rhythms in mammals, including the sleep-wake cycle, appears to be located in the suprachiasmatic nucleus, and recent research indicates that both cell bodies and axons containing GABA are present within the bilaterally paired suprachiasmatic nuclei. These findings raise the possibility that the benzodiazepines, commonly prescribed for sleep and mental disorders, may have an effect on the central circadian pacemaker. Here we report that the acute administration of triazolam, a short-acting benzodiazepine commonly prescribed for the treatment of insomnia, induces a phase-shift in the circadian rhythm of locomotor activity in golden hamsters. This suggests a role for GABA-containing neurones in the mammalian circadian system.     

Odour-modulated collective network oscillations of olfactory interneurons in a terrestrial mollusc

Determination of the dynamical structure of neural circuits--the general principles of how neural activity varies with time and manipulates information--is a prerequisite to understanding their computational function. Rhythmically active or oscillating neural circuits are particularly interesting dynamical structures, as rhythms and oscillations are a prominent feature of mammalian central nervous system electrophysiology. Coherent oscillations by networks of interneurons are observed in the vertebrate olfactory system and have recently been described in mammalian visual cortex. These interneuronal networks display oscillations in local field potential (LFP) and probability of producing action potentials that are highly correlated between subcircuits sharing the same stimulus features. Much less is known about the existence and importance of network oscillations in the higher centres of invertebrates. Here we report that a network of olfactory interneurons in the cerebral ganglion of the terrestrial mollusc Limax maximus also displays coherent oscillations in LFP which are modified by odour input. This dynamical structure could be central to the odour recognition and odour learning ability of Limax.     

芦笋老茎培养料对姬松茸产量、多糖含量和抗氧化性的影响

设计了以芦笋老茎为主料,棉籽壳、玉米芯、干牛粪和杂木屑为辅料的4种培养料栽培姬松茸,玉米秸秆培养料作为对照.结果表明姬松茸在芦笋老茎和玉米秸秆培养料上的产量没有明显差异(P＜0.05);添加棉籽壳或干牛粪的芦笋老茎培养料其姬松茸产量明显高于添加杂木屑或玉米芯的芦笋老茎培养料(P＜0.05).芦笋老茎培养料上栽培得到的姬松茸子实体的抗氧化性明显高于对照培养料上栽培得到的子实体的抗氧化性(P＜0.05),但多糖含量却明显低于对照(P＜0.05);4种辅料对姬松茸子实体的多糖含量和抗氧化性有一定的影响.     

Chemical codes for the control of behaviour in arthropods

Neuromodulators and hormones elicit and modify well-defined behaviours. Their mode of action can be studied to advantage in arthropods, where the natural releasing cells and neuronal target circuits are concisely identified. The coordinated actions of biogenic amines and peptides on both central and peripheral neural activity and metabolic processes bias the whole organism to perform a coherent behavioural routine.     

神经元及神经环路活性异常与阿尔茨海默病研究进展

 细胞外淀粉样蛋白（Aβ）沉积和细胞内神经纤维缠结是阿尔茨海默病的典型病理特征。淀粉样蛋白和tau蛋白（神经纤维缠结的主要组成成分）在脑中的异常聚集会导致神经元活性异常,进而引起神经环路结构及功能紊乱,最终造成阿尔茨海默病患者认知功能障碍。概述了Aβ及tau蛋白的生成及调控,阐述了Aβ及tau蛋白异常聚集在神经元及神经环路活动中的作用和机制,综述了ApoE、炎症反应及成体神经发生异常在AD神经元及神经环路活动障碍中的作用。     

Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina

Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them. These lamina-specific circuits determine the visual features to which RGC subtypes respond. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2 (ref. 10)--are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.     

平菇栽培中病原菌的调查研究

防治病虫害是搞好食用菌生产的重要环节。作者于1986～1988年在新乡市(县)范围内进行了平菇栽培中病原菌的调查研究。分离、鉴定出病原细菌3属:病原真菌13属。调查发现,平菇栽培中病原菌极易发生且具有规律性:在菌种培植和菌丝发育阶级最易污染杂菌,主要是真菌和细菌;在子实体形成和成熟采收阶段,除部分杂菌继续蔓延外,害虫逐渐盛行,给平菇生产造成极大危害。由于平菇特有的栽培方式和食用特点,采取“以防为主、综合防治”的方法,更具有特殊意义。     

基于柔性免疫神经树的模拟电路故障诊断方法

模拟电路的非线性特性、连续性和元器件的容差等因素给故障的建模分析造成了诸多不确定因素,因此其智能故障诊断方法的研究至关重要。柔性神经树是一种采用树形结构和一组运算符集合构成的新型神经网络,与传统神经网络相比具有更加灵活的自动优化能力。本文将人工免疫机理融入柔性神经树,提出了一种基于柔性免疫神经树的模拟电路故障诊断方法。通过对一种典型模拟电路的故障诊断仿真试验,证明了该方法的有效性和可行性。     

A gene expression atlas of the central nervous system based on bacterial artificial chromosomes

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.     

MOS VLSI电流型模拟电子神经网络

本文提出了采用ＭＯＳ晶体管的电流型模拟电子神经网络的新实现。该电路结构非常简单，且具有ＭＯＳ ＶＬＳＩ的优点，新的神经元电路的神经态既可以是全电流型又可以是电压型。     

基于KuhnTucker方法的机组最优投入神经网络模型

为了用硬件实现机组优化投入的神经计算，首先基于ＫｕｈｎＴｕｃｋｅｒ方法的机组最优投入神经网络模型。证明了该模型的收敛性，讨论了该模型的正则电路，并用ＰＳＰＩＣＥ５０对一个四机组四时段的系统进行仿真计算。     

Loss of autophagy in the central nervous system causes neurodegeneration in mice

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.     

一种模糊神经网络的硬件电路优化设计方式

为提高模拟电路实现模糊神经网络的精度,通过对模糊神经网络中的高斯函数电路、求小电路以及去模糊电路分别进行性能优化,从整体上达到模拟电路实现模糊神经网络中高精度、高速的特性要求.所设计的模糊神经网络整体电路采用电压模式实现,并通过逼近一个非线性函数来验证.所设计的模拟单元电路均采用TSMC 0.18 μm工艺参数设计完成.通过Cadence软件仿真,结果表明:在1.8 V的工作电压下,所提出的改进型单元电路具有精度高、结构简单、便于调节和扩展的特性,并且能够完整地实现模糊神经网络的控制.     

Hierarchical Neural Networks Method for Fault Diagnosis of Large-Scale Analog Circuits

A novel hierarchical neural networks (HNNs) method for fault diagnosis of large-scale circuits is proposed. The presented techniques using neural networks(NNs) approaches require a large amount of computation for simulating various faulty component possibilities. For large scale circuits, the number of possible faults, and hence the simulations, grow rapidly and become tedious and sometimes even impractical. Some NNs are distributed to the torn sub-blocks according to the proposed torn principles of large scale circuits. And the NNs are trained in batches by different patterns in the light of the presented rules of various patterns when the DC, AC and transient responses of the circuit are available. The method is characterized by decreasing the over-lapped feasible domains of responses of circuits with tolerance and leads to better performance and higher correct classification. The methodology is illustrated by means of diagnosis examples.     

Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory

Surgical, pharmacological and genetic lesion studies have revealed distinct anatomical sites involved with different forms of learning. Studies of patients with localized brain damage and work in rodent model systems, for example, have shown that the hippocampal formation participates in acquisition of declarative tasks but is not the site of their long-term storage. Such lesions are usually irreversible, however, which has limited their use for dissecting the temporal processes of acquisition, storage and retrieval of memories. Studies in bees and flies have similarly revealed a distinct anatomical region of the insect brain, the mushroom body, that is involved specifically in olfactory associative learning. We have used a temperature-sensitive dynamin transgene, which disrupts synaptic transmission reversibly and on the time-scale of minutes, to investigate the temporal requirements for ongoing neural activity during memory formation. Here we show that synaptic transmission from mushroom body neurons is required during memory retrieval but not during acquisition or storage. We propose that the hebbian processes underlying olfactory associative learning reside in mushroom body dendrites or upstream of the mushroom body and that the resulting alterations in synaptic strength modulate mushroom body output during memory retrieval.