The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs

The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane’s inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite–soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.     

Formation of segregated regions of feature detecting cells in self-organizing nerve field

This paper investigates the formation of a segregated region for a specific set of input signals in a nerve field. The segregated region is formed by a feature detecting cell group which fires only for a specific set of input signals. This firing region is called the region of feature detecting cells for the corresponding input set. First, a basic self-organizing model is given. The model is composed of the first input layer, the second nerve cell layer with lateral inhibitory interactions (it is called a lateral-inhibition type nerve field) and an inhibitory nerve cell. An input signal is an-dimensional vector whose components assume continuous values. Next, the condition which gurantees the formation of a segregated region for a specific set of input signals is derived, and the properties of the model are discussed based on the derived condition. In addition, the behavior of the model is examined through computer-simulated experiments. The following observations are made: When a certain condition is satisfied, a segregated region is formed in the nerve field according to a specific set of input signals. By varying the parameters of learning, the region is formed depending on the similarity between input signals. The regions for similar input signals are formed near each other in the nerve field. The region is created depending on the occurence probability of the input signal and its norm.     

Expanding the chemical functionality of DNA nanomaterials generated by rolling circle amplification

Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present orthogonal strategies to produce densely modified RCA products and DNFs. We provide methods to selectively modify the DNA component and/or the protein cargo of these materials, thereby greatly expanding the range of chemical functionalities available to these systems. We have used our methodology to construct DNFs bearing multiple surface aptamers and peptides capable of binding to cancer cells that overexpress the HER2 oncobiomarker, demonstrating their potential for diagnostic and therapeutic applications.     

黄河三角洲滨岸潮滩湿地碱蓬对水沙条件及氮输入的适应性

调水调沙工程的实施为黄河三角洲带来大量淡水恢复退化湿地的同时,也改变了湿地的水沙状况并带来大量的外源物质。本研究采用3因素4水平的正交试验,以黄河口滨岸潮滩湿地典型的先锋物种碱蓬为研究对象,探讨了其对淹水深度、泥沙埋深及外源氮输入的适应机制。结果表明: 泥沙埋深对碱蓬叶片蛋白含量及超氧化物歧化酶(SOD)活性的影响较大;氮输入对过氧化物酶(POD)活性的影响较大,而3种处理对过氧化氢酶(CAT)活性的影响无显著差异。淹水深度对叶、茎及总干重具有显著影响,且随淹水深度的增加呈现减小趋势,最大值(25.70、40.86、69.73 g)均出现在2 cm淹水处理;而氮输入及泥沙埋深对碱蓬干重的影响不显著。极差分析表明,淹水深度对碱蓬叶、茎、根及总干重的影响最为显著,其次为氮输入和泥沙埋深,2 cm淹水深度+12 cm埋深深度+9 g·m^-2氮输入量最有利于碱蓬的生长。可见,淹水深度的变化对碱蓬的生长起到决定性的作用,在调水调沙等工程的实施过程中应注重淹水深度的把控。     

农田秸秆覆盖对冬小麦水氮效应的影响

通过田间试验研究了杨凌红油土农田秸秆覆盖条件下冬小麦的水氮效应.结果表明,秸秆覆盖使土壤水分状况明显改善,从而使补充灌水的效果相应减小,氮肥的作用更加突出;无覆盖条件下,水氮交互效应均为负值,而秸秆覆盖时水氮有正的交互作用.旱地秸秆覆盖条件下更应重视养分的投入.无秸秆覆盖条件下小麦取得高产的基础是良好的土壤底墒和充足的氮肥.秸秆覆盖使小麦达到最高产量所需要的灌水量降低,灌水时期后延.不论有无秸秆覆盖,拔节期灌水对冬小麦籽粒产量没有显著影响.     

静水与流水下气泡幕对异齿裂腹鱼的阻拦效应

为了探究不同水流条件下不同形式的气泡幕对异齿裂腹鱼(Schizothorax oconnori)趋避行为的影响。在黑暗环境下测试了两种流速条件(静水与流水)、三种气量(15、30、45 L/min)及两种摆放角度(与水流方向呈90°和45°)的气泡幕对异齿裂腹鱼的阻拦效果,在静水和流水条件下各设置一组空白对照(气量为0 L/min)。结果显示: (1)在静水条件下, 工况2阻拦率最高(50%); 在流水条件下, 工况7阻拦率最高(50%)。(2)气量15 L/min时, 流水及90°摆放阻拦时间显著大于其他工况; 30 L/min时, 静水及90°摆放阻拦时间远大于其他工况。(3)在静水和流水中, 当异齿裂腹鱼尝试次数达到6次左右时对气泡幕表现出适应性, 并在48min前通过气泡幕; (4)在流水中各工况下气泡幕的影响距离显著大于静水(P<0.05), 即异齿裂腹鱼产生逃逸行为时距离气管的距离显著大于静水中。研究可得出结论: 推荐阻拦效果最佳的组合方式为流水条件下15 L/min 90°摆放(工况7)、静水条件下30 L/min 90°摆放(工况2); 气泡幕连续阻拦时间不宜超过48min。实验结果可为实际工程中气泡幕的布置提供参考。     

Asymmetry in neural fields: a spatiotemporal encoding mechanism

Neural field models have been successfully applied to model diverse brain mechanisms like visual attention, motor control, and memory. Most theoretical and modeling works have focused on the study of the dynamics of such systems under variations in neural connectivity, mainly symmetric connectivity among neurons. However, less attention has been given to the emerging properties of neuron populations when neural connectivity is asymmetric, although asymmetric activity propagation has been observed in cortical tissue. Here we explore the dynamics of neural fields with asymmetric connectivity and show, in the case of front propagation, that it can bias the population to follow a certain trajectory with higher activation. We find that asymmetry relates linearly to the input speed when the input is spatially localized, and this relation holds for different kernels and input shapes. To illustrate the behavior of asymmetric connectivity, we present an application: standard video sequences of human motion were encoded using the asymmetric neural field and compared to computer vision techniques. Overall, our results indicate that asymmetric neural fields are a competitive approach for spatiotemporal encoding with two main advantages: online classification and distributed operation.     

三相鼓泡塔生物反应器培养云芝菌合成漆酶

为了提高云芝菌发酵生产漆酶的效率,提出了一种利用自絮凝菌丝球在三相鼓泡塔生物反应器中重复分批发酵产漆酶的新方法。在优化后的产酶条件下,考察维生素C的添加浓度对漆酶活力的影响,并通过在培养基中添加维生素C进行漆酶多批次培养。研究结果表明,维生素C的添加浓度为1.50mmol/L时,可使漆酶活力提高2.6倍。连续进行了10批培养,每批最大漆酶的活力均在1000 U/mL以上,最高酶活出现在第五批为1919.6 U/mL,总培养时间达25 d。此方法所得漆酶对染料靛蓝具有明显的脱色降解作用,在介体1-羟基苯并三唑（HBT）用量0.10%,漆酶用量100 U/L条件下作用40 min时,靛蓝脱色率达到96.7%。该方法采用的三相鼓泡塔生物反应器性能稳定、菌丝球可重复使用,该方法有利于漆酶的高效、规模化生产。     

Decision, sensation, and habituation: a multi-layer dynamic field model for Inhibition of Return

Inhibition of Return (IOR) is one of the most consistent and widely studied effects in experimental psychology. The effect refers to a delayed response to visual stimuli in a cued location after initial priming at that location. This article presents a dynamic field model for IOR. The model describes the evolution of three coupled activation fields. The decision field, inspired by the intermediate layer of the superior colliculus, receives endogenous input and input from a sensory field. The sensory field, inspired by earlier sensory processing, receives exogenous input. Habituation of the sensory field is implemented by a reciprocal coupling with a third field, the habituation field. The model generates IOR because, due to the habituation of the sensory field, the decision field receives a reduced target-induced input in cue-target-compatible situations. The model is consistent with single-unit recordings of neurons of monkeys that perform IOR tasks. Such recordings have revealed that IOR phenomena parallel the activity of neurons in the intermediate layer of the superior colliculus and that neurons in this layer receive reduced input in cue-target-compatible situations. The model is also consistent with behavioral data concerning temporal expectancy effects. In a discussion, the multi-layer dynamic field account of IOR is used to illustrate the broader view that behavior consists of a tuning of the organism to the environment that continuously and concurrently takes place at different spatiotemporal scales.     

Chromosomal aberrations induced in vitro by 3,7- and 3,9-dinitrofluoranthene

The chromosomal aberration test using a Chinese hamster cell line (CHL) was carried out with 3,7- and 3,9-dinitrofluoranthene (DNF) with and without exogenous metabolic activation (rat liver S9 mix). The highest dose tested was limited to 20 μg/ml because of the compounds' insolubility in dimethyl sulfoxide. Both DNFs induced chromosomal aberrations in the absence of S9 mix; the frequency was not very high. Results were reproducible, but without clear dose-response relationships. Neither DNF induced chromosomal aberrations in the presence of S9 mix. Both DNFs did not induce polyploid cells under any conditions.     

Bursting as an Effective Relay Mode in a Minimal Thalamic Model

In recent years, accumulating evidence indicates that thalamic bursts are present during wakefulness and participate in information transmission as an effective relay mode with distinctive properties from the tonic activity. Thalamic bursts originate from activation of the low threshold calcium cannels via a local feedback inhibition, exerted by the thalamic reticular neurons upon the relay neurons. This article, examines if this simple mechanism is sufficient to explain the distinctive properties of thalamic bursting as an effective relay mode. A minimal model of thalamic circuit composed of a retinal spike train, a relay neuron and a reticular neuron is simulated to generate the tonic and burst firing modes. The integrate-and-fire-or-burst model is used to simulate the neurons. After discriminating the burst events with criteria based on inter-spike-intervals, statistical indices show that the bursts of the minimal model are stereotypic events. The relation between the rate of bursts and the parameters of the input spike train demonstrates marked nonlinearities. Burst response is shown to be selective to spike-silence-spike sequences in the input spike train. Moreover, burst events represent the input more reliably than the tonic spike in a considerable range of the parameters of the model. In conclusion, many of the distinctive properties of thalamic bursts such as stereotypy, nonlinear dependence on the sensory stimulus, feature selectivity and reliability are reproducible in the minimal model. Furthermore, the minimal model predicts that while the bursts are more frequent in the spike train of the off-center X relay neurons (corresponding to off-center X retinal ganglion cells), they are more reliable when generated by the on-center ones (corresponding to on-center X ganglion cells).     

Computer simulations of synchrony and oscillations evoked by two coherent inputs

Coherent oscillations have been reported in multiple cortical areas. This study examines the characteristics of output spikes through computer simulations when the neural network model receives periodic/aperiodic spatiotemporal spikes with modulated/constant populational activity from two pathways. Synchronous oscillations which have the same period as the input are observed in response to periodic input patterns regardless of populational activity. The results confirm that the output frequency of synchrony is essentially determined by the period of the repeated input patterns. On the other hand, weak periodic outputs are observed when aperiodic spikes are input with modulated populational activity. In this case, higher firing rates are necessary to input for higher frequency oscillations. The spike-timing-dependent plasticity suppresses the spikes which do not contribute to the synchrony for periodic inputs. This effect corresponds to the experimental reports that learning sharpens the synchrony in the motor cortex. These results suggest that spatiotemporal spike patterns should be entrained on modulated populational activity to transmit oscillatory information effectively in the convergent pathway.     

Synaptic inputs to the ganglion cells in the tiger salamander retina

The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.     

Membrane sparger in bubble column,airlift, and combined membrane–ring sparger bioreactors

The bubble column and the two internal loop airlift reactors (riser/downcomer area ratios of 0.11 and 0.58) characterized in this study were equipped with a rubber membrane sparger, which produced small bubbles, giving high mass transfer coefficients. The low mixing intensity in the bubble column was increased by an order of magnitude in the airlift reactors. We designed a novel aeration and mixing system by adding a ring sparger to the membrane sparger in the bubble column and maintained the advantages of both airlift configuration (good mixing properties) and bubble column configuration (efficient aeration, without any internal constructions). The combined membrane–ring sparger system has unique features with respect to the efficiency of utilization of substrate gasses and energy. Model experiments showed that the small bubbles from the membrane sparger do not coalesce with the large bubbles from the ring sparger. If different gases were added through the two spargers it was possible to transfer a hazardous or expensive gas quantitatively to the liquid through the membrane sparger (dual sparging mode). In the combined membrane–ring sparger system the energy input for mixing and mass transfer is divided. Therefore, the energy consumption can be minimized if the flow distribution of air through the membrane and ring sparger is controlled by the oxygen demand and the inhomogeneity of the culture, respectively (split sparging mode). The dual sparging mode was used for mass production of the alga Rhodomonas sp. as the first step in aquatic food chains. Avoiding mechanical parts removes an important risk of malfunction, and a continuous culture could be maintained for more than 8 months. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 452–458, 1999.     

Domain swapping between FEN-1 and XPG defines regions in XPG that mediate nucleotide excision repair activity and substrate specificity

FEN-1 and XPG are members of the FEN-1 family of structure-specific nucleases, which share a conserved active site. FEN-1 plays a central role in DNA replication, whereas XPG is involved in nucleotide excision repair (NER). Both FEN-1 and XPG are active on flap structures, but only XPG cleaves bubble substrates. The spacer region of XPG is dispensable for nuclease activity on flap substrates but is required for NER activity and for efficient processing of bubble substrates. Here, we inserted the spacer region of XPG between the nuclease domains of FEN-1 to test whether this domain would be sufficient to confer XPG-like substrate specificity and NER activity on a related nuclease. The resulting FEN-1-XPG hybrid protein is active on flap and, albeit at low levels, on bubble substrates. Like FEN-1, the activity of FEN-1-XPG was stimulated by a double-flap substrate containing a 1-nt 3′ flap, whereas XPG does not show this substrate preference. Although no NER activity was detected in vitro, the FEN-1-XPG hybrid displays substantial NER activity in vivo. Hence, insertion of the XPG spacer region into FEN-1 results in a hybrid protein with biochemical properties reminiscent of both nucleases, including partial NER activity.     

An MLP training algorithm taking into account known errors on inputs and outputs

A training algorithm is introduced that takes into account a priori known errors on both inputs and outputs in an MLP network. The new cost function introduced for this case is based on a linear approximation of the network function over the input distribution for a given input pattern. Update formulas, in the form of the gradient of the new cost function, is given for a MLP network, together with expressions for the Hessian matrix. This is later used to calculate error bars in a Bayesian framework. The error bars thus derived are discussed in relation to the more commonly used width of the target posterior predictive distribution. It will also be shown that the taking into account of known input uncertainties in the way suggested in this article will have a strong regularizing effect on the solution.     

Origin and properties of striatal local field potential responses to cortical stimulation: temporal regulation by fast inhibitory connections

Evoked striatal field potentials are seldom used to study corticostriatal communication in vivo because little is known about their origin and significance. Here we show that striatal field responses evoked by stimulating the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA receptor antagonist CNQX close to the recording electrode. Moreover, the amplitude of local field responses and dPSPs recorded in striatal medium spiny neurons increase in parallel with increasing stimulating current intensity. Finally, the evoked striatal fields show several of the basic known properties of corticostriatal transmission, including paired pulse facilitation and topographical organization. As a case study, we characterized the effect of local GABA(A) receptor blockade on striatal field and multiunitary action potential responses to prelimbic cortex stimulation. Striatal activity was recorded through a 24 channel silicon probe at about 600 μm from a microdialysis probe. Intrastriatal administration of the GABA(A) receptor antagonist bicuculline increased by 65±7% the duration of the evoked field responses. Moreover, the associated action potential responses were markedly enhanced during bicuculline infusion. Bicuculline enhancement took place at all the striatal sites that showed a response to cortical stimulation before drug infusion, but sites showing no field response before bicuculline remained unresponsive during GABA(A) receptor blockade. Thus, the data demonstrate that fast inhibitory connections exert a marked temporal regulation of input-output transformations within spatially delimited striatal networks responding to a cortical input. Overall, we propose that evoked striatal fields may be a useful tool to study corticostriatal synaptic connectivity in relation to behavior.     

Process-engineering characterization of small-scale bubble columns for microbial process development

Volumetric oxygen transfer rates and power inputs were estimated by a model of the formation of primary gas bubbles at the static sparger (sinter plate) of small-scale bubble columns and a common mass-transfer correlation for bubbles rising in a non-coalescent Newtonian electrolyte solution of low viscosity. Estimations were used to assess the dimensioning and possibilities of small-scale bubble column application with an height/diameter ratio of about 1. Estimations of volumetric oxygen transfer rates (<0.16 s^-1) and power inputs (<100 W m^-3) with a mean pore diameter of the static sparger of 13 µm were confirmed as function of the superficial air velocity (<0.6 cm s^-1) by measurements using an Escherichia coli fermentation medium. Small-scale bubble columns are thus to be classified between shaking flasks and stirred-tank reactors with respect to the oxygen transfer rate, but the maximum volumetric power input is more than one magnitude below the power input in shaking flasks, which is of the same order of magnitude as in stirred-tank reactors. A small-scale bubble columns system was developed for microbial process development, which is characterized by handling in analogy to shaking flasks, high oxygen transfer rates and simultaneous operation of up to 16 small-scale reactors with individual gas supply in an incubation chamber.     

Can diving-induced tissue nitrogen supersaturation increase the chance of acoustically driven bubble growth in marine mammals?

The potential for acoustically mediated causes of stranding in cetaceans (whales and dolphins) is of increasing concern given recent stranding events associated with anthropogenic acoustic activity. We examine a potentially debilitating non-auditory mechanism called rectified diffusion. Rectified diffusion causes gas bubble growth, which in an insonified animal may produce emboli, tissue separation and high, localized pressure in nervous tissue. Using the results of a dolphin dive study and a model of rectified diffusion for low-frequency exposure, we demonstrate that the diving behavior of cetaceans prior to an intense acoustic exposure may increase the chance of rectified diffusion. Specifically, deep diving and slow ascent/descent speed contributes to increased gas-tissue saturation, a condition that amplifies the likelihood of rectified diffusion. The depth of lung collapse limits nitrogen uptake per dive and the surface interval duration influences the amount of nitrogen washout from tissues between dives. Model results suggest that low-frequency rectified diffusion models need to be advanced, that the diving behavior of marine mammals of concern needs to be investigated to identify at-risk animals, and that more intensive studies of gas dynamics within diving marine mammals should be undertaken.