动态突触、神经耦合与时间延迟对神经元发放的影响

神经元膜电位的受激发放在神经系统的信息传递中起着重要作用.基于一个受动态突触刺激的突触后神经元发放模型,采用数值模拟和傅里叶变换分析的方法研究了动态突触、神经耦合与时间延迟对突触后神经元发放的影响.结果发现:突触前神经元发放频率与Hodgkin-Huxley神经元的固有频率发生共振决定了突触后神经元发放的难易,特定频率范围内的电流刺激有利于神经元激发,动态突触输出的随机突触电流中这些电流刺激所占的比率在很大程度上影响了突触后神经元的发放次数;将突触后神经元换成神经网络后,网络中神经元之间的耦合可以促进神经元的发放,耦合中的时间延迟可以增强这种促进作用,但是不会改变神经耦合对神经元发放的促进模式.     

Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment

ABSTRACT: BACKGROUND: Cognitive impairment associated with subtle changes in neuron and neuronal network function rather than widespread neuron death is a feature of the normal aging process in humans and animals. Despite its broad evolutionary conservation, the etiology of this aging process is not well understood. However, recent evidence suggests the existence of a link between oxidative stress in the form of progressive membrane lipid peroxidation, declining neuronal electrical excitability and functional decline of the normal aging brain. The current study applies a combination of behavioural and electrophysiological techniques and pharmacological interventions to explore this hypothesis in a gastropod model (Lymnaea stagnalis feeding system) that allows pinpointing the molecular and neurobiological foundations of age-associated long-term memory (LTM) failure at the level of individual identified neurons and synapses. RESULTS: Classical appetitive reward-conditioning induced robust LTM in mature animals in the first quartile of their lifespan but failed to do so in animals in the last quartile of their lifespan. LTM failure correlated with reduced electrical excitability of two identified serotonergic modulatory interneurons (CGCs) critical in chemosensory integration by the neural network controlling feeding behaviour. Moreover, while behavioural conditioning induced delayed-onset persistent depolarization of the CGCs known to underlie appetitive LTM formation in this model in the younger animals, it failed to do so in LTM-deficient senescent animals. Dietary supplementation of the lipophilic anti-oxidant alpha-tocopherol reversed the effect of age on CGCs electrophysiological characteristics but failed to restore appetitive LTM function. Treatment with the SSRI fluoxetine reversed both the neurophysiological and behavioural effects of age in senior animals. CONCLUSIONS: The results identify the CGCs as cellular loci of age-associated appetitive learning and memory impairment in Lymnaea and buttress the hypothesis that lipid peroxidation-dependent depression of intrinsic excitability is a hallmark of normal neuronal aging. The data implicate both lipid peroxidation-dependent non-synaptic as well as apparently lipid peroxidation-independent synaptic mechanisms in the age-dependent decline in behavioural plasticity in this model system.     

Translational medicine of the glutamate AMPA receptor

Psychiatric and neurological disorders severely hamper patient’s quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are essential structural units of neurotransmission, and neuropsychiatric disorders are considered as “synapse diseases”. Thus, a translational approach with synaptic physiology is crucial to tackle these disorders. Among a variety of synapses, excitatory glutamatergic synapses play central roles in neuronal functions. The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a principal component of glutamatergic neurotransmission; therefore, it is considered to be a promising translational target. Here, we review the limitations of current diagnostics and therapeutics of neuropsychiatric disorders and advocate the urgent need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Furthermore, we introduce our recent translational approach to these disorders by targeting at AMPARs.     

Delay-induced synchronization transitions in small-world neuronal networks with hybrid electrical and chemical synapses

We study the dependence of synchronization transitions in small-world networks of bursting neurons with hybrid electrical–chemical synapses on the information transmission delay, the probability of electrical synapses, and the rewiring probability. It is shown that, irrespective of the probability of electrical synapses, the information transmission delay can always induce synchronization transitions in small-world neuronal networks, i.e., regions of synchronization and nonsynchronization appear intermittently as the delay increases. In particular, all these transitions to burst synchronization occur approximately at integer multiples of the bursting period of individual neurons. In addition, for larger probability of electrical synapses, the intermittent synchronization transition is more profound, due to the stronger synchronization ability of electrical synapses compared with chemical ones. More importantly, chemical and electrical synapses can perform complementary roles in the synchronization of hybrid small-world neuronal networks: the larger the electrical synapse strength is, the smaller the chemical synapse strength needed to achieve burst synchronization. Furthermore, the small-world topology has a significant effect on the synchronization transition in hybrid neuronal networks. It is found that increasing the rewiring probability can always enhance the synchronization of neuronal activity. The results obtained are instructive for understanding the synchronous behavior of neural systems.     

小世界神经元网络随机共振现象:混合突触和部分时滞的影响

实际神经元网络中,信息传递时电突触和化学突触同时存在,并且有些神经元间的时滞很小可以忽略.本文构建了带有不同类型突触耦合的小世界网络,研究部分时滞、混合突触及噪声对随机共振的影响.结果表明:兴奋性和抑制性突触的比例影响共振的产生;在抑制性突触为主的网络里,几乎不产生随机共振.系统最佳噪声强度和化学突触比例大致呈线性递增关系;特别是在以化学耦合为主的混合突触网络里,仅当兴奋性突触与抑制性突触比例约为4:1时,噪声才可诱导网络产生共振行为.在此比例下,引入部分时滞发现时滞可诱导网络产生随机多共振,且随网络中时滞边比例的增加,系统响应强度达到最优水平的时滞取值区间逐渐变窄;同时发现,网络中含有的化学突触越多,部分时滞诱导产生的多共振行为越强.此外,当时滞为系统固有周期的整数倍时,时滞越大共振所对应的噪声区域越广;并且网络中时滞边越多,越容易促使噪声和时滞诱导其产生明显的共振行为.     

Escape Through a Small Opening: Receptor Trafficking in a Synaptic Membrane

We model the motion of a receptor on the membrane surface of a synapse as free Brownian motion in a planar domain with intermittent trappings in and escapes out of corrals with narrow openings. We compute the mean confinement time of the Brownian particle in the asymptotic limit of a narrow opening and calculate the probability to exit through a given small opening, when the boundary contains more than one. Using this approach, it is possible to describe the Brownian motion of a random particle in an environment containing domains with small openings by a coarse grained diffusion process. We use the results to estimate the confinement time as a function of the parameters and also the time it takes for a diffusing receptor to be anchored at its final destination on the postsynaptic membrane, after it is inserted in the membrane. This approach provides a framework for the theoretical study of receptor trafficking on membranes. This process underlies synaptic plasticity, which relates to learning and memory. In particular, it is believed that the memory state in the brain is stored primarily in the pattern of synaptic weight values, which are controlled by neuronal activity. At a molecular level, the synaptic weight is determined by the number and properties of protein channels (receptors) on the synapse. The synaptic receptors are trafficked in and out of synapses by a diffusion process. Following their synthesis in the endoplasmic reticulum, receptors are trafficked to their postsynaptic sites on dendrites and axons. In this model the receptors are first inserted into the extrasynaptic plasma membrane and then random walk in and out of corrals through narrow openings on their way to their final destination.     

Accelerating vinegar aging by combination of ultrasonic and magnetic field assistance

Most fermented foods need a natural aging process to enrich desired flavours. This process is normally the bottleneck for cost-effective production. Therefore, it is desirable to accelerate the process and obtain products with the same flavour profile. Here, we used physical interventions (ultrasonic field, alternating magnetic field, or combination of both) to assist the aging process with naturally brewed vinegar as a case example. Flavour profiles of different physical-assisted aging process were compared with that of the naturally aged vinegar by using gas-chromatography mass-spectrometry (GC–MS) and electronic nose. Principal component analysis (PCA) and Pearson correlation analyses show that ultrasonic and alternating magnetic fields treatment could accelerate the aging process of vinegar. The highest accelerating aging effect was combination of ultrasonic and magnetic field followed by individual ultrasonic or magnetic field and natural process (combination of ultrasonic and magnetic field > ultrasonic or magnetic field individual > natural process). These results suggest that physical field intervention could potentially be used for acceleration of aging of fermented products without affecting flavour quality.     

A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats

Ketogenic diets (KDs) have been applied in the therapy of paediatric epilepsy for nearly a century. Recently, beneficial results have also been reported on metabolic disorders and neurodegeneration, designating aged individuals as possible recipients. However, KDs efficacy decrease after the suckling period, and very little is known about their impact on the aging brain. In the present study, the effect on the neuronal energetic supply of a KD containing 20% of medium chain triglycerides (MCT) was investigated in Purkinje cells of the cerebellar vermis of late-adult (19-month-old) rats. The animals were fed with the KD for 8 weeks, and succinic dehydrogenase (SDH) activity was cytochemically determined. The following parameters of SDH-positive mitochondria were evaluated by the use of a computer-assisted image analysis system connected to a transmission electron microscope: numeric density (Nv), average volume (V), volume density (Vv), and cytochemical precipitate area/mitochondrial area (R). Young, age-matched, and old animals fed with a standard chow were used as controls. We found significantly higher Nv in MCT-KD-fed rats vs. all the control groups, in young vs. late-adult and old controls, and in late-adult vs. old controls. V and Vv showed no significant differences among the groups. R was significantly higher in MCT-KD-fed rats vs. all the control animals, and in old vs. young and late-adult controls. Present data indicate that the ketogenic treatment counteracted age-related decrease in numeric density of SDH-positive mitochondria, and enhanced their metabolic efficiency. Given the central role of mitochondrial impairment in age-related physio-pathological changes of the brain, these findings may represent a starting point to examine novel potentialities for KDs.     

Strength and precision of neurotransmission at mammalian presynaptic terminals

Classically, the basic concept of chemical synaptic transmission was established at the frog neuromuscular junction, and direct intracellular recordings from presynaptic terminals at the squid giant presynaptic terminal have further clarified principles of neurotransmitter release. More recently, whole-cell patch-camp recordings from the calyx of Held in rodent brainstem slices have extended the classical concept to mammalian synapses providing new insights into the mechanisms underlying strength and precision of neurotransmission and developmental changes therein. This review summarizes findings from our laboratory and others on these subjects, mainly at the calyx of Held, with a particular focus on precise, high-fidelity, fast neurotransmission. The mechanisms by which presynaptic terminals acquire strong, precise neurotransmission during postnatal development are also discussed.     

Neural signal transduction aided by noise in multisynaptic excitatory and inhibitory pathways with saturation

We study the stochastic resonance phenomenon in saturating dynamical models of neural signal transduction, at the synaptic stage, wherein the noise in multipathways enhances the processing of neuronal information integrated by excitatory and inhibitory synaptic currents. For an excitatory synaptic pathway, the additive intervention of an inhibitory pathway reduces the stochastic resonance effect. However, as the number of synaptic pathways increases, the signal transduction is greatly improved for parallel multipathways that feature both excitation and inhibition. The obtained results lead us to the realization that the collective property of inhibitory synapses assists neural signal transmission, and a parallel array of neurons can enhance their responses to multiple synaptic currents by adjusting the contributions of excitatory and inhibitory currents.     

Influence of Food Restriction and Compensatory Growth on Protein Synthesis and Breakdown in Growing Rats

The experiment was carried out with 24 male albino rats (5 weeks old, live weight 79 ± 5.1 g) divided into 2 groups. Gr. 1 (control group) was fed the commercial breeding food Ssniff with 22.4% crude protein ad lib., Gr. 2 (test group) for the first fortnight a mixture of the breeding food/cellulose 60/40 (restriction period) and subsequently for the second fortnight (compensatory period) also the breeding food ad lib. During both of these periods an 8 day N balance trial and a 4 day ¹⁵N tracer trial were included for estimation of growth rate and protein synthesis rate. Protein synthesis was ascertained by the endproduct method (oral application, single dose, mixture of 12 ¹⁵N-labelled amino acids); protein breakdown was calculated as the difference of protein synthesis rate and growth rate. The estimated rates were converted into fractional ones by referring to the body N content of corresponding animals. From the results of this experiment is concluded: The smaller N balance during moderate nutritional restriction can be attributed to a decrease of protein synthesis. The compensatory growth of the animals during the realimentation period is caused by an increase of protein synthesis and the enhanced protein conversion. Protein degradation is nearly unaffected.     

稻米陈化中谷蛋白变化光谱解析及其对功能性质的影响

稻米储藏陈化导致食用品质下降,蛋白质变化是重要诱因。谷蛋白是稻米中主要蛋白,采用拉曼和红外光谱表征陈化中谷蛋白的变化,并对其功能性质差异进行比较,利于阐明稻米的陈化机理。拉曼光谱表明,陈米谷蛋白1 665和1 218 cm-1处的拉曼归一化强度分别为1.01和0.25,明显低于新米谷蛋白,表明陈化后谷蛋白的α-螺旋减少;陈米谷蛋白中二硫键(516和527 cm-1处峰强度分别为0.45和0.42)、亚砜(1 035 cm-1处峰强度为0.48)和砜(1 124,1 152,1 159,1 316和1 334 cm-1处峰强度分别为0.47,0.22,0.26,0.50和0.63)的强度明显高于新米谷蛋白,表明含硫氨基酸残基发生明显氧化;陈米谷蛋白的酪氨酸Fermi共振857/830 cm-1的强度比值1.68明显高于新米谷蛋白,酪氨酸残基更加暴露;陈米谷蛋白751 cm-1附近色氨酸的拉曼强度为0.20,比新米谷蛋白的强度0.14显著提高,陈化后谷蛋白色氨酸残基更加埋藏;陈米谷蛋白3 423 cm-1处的O-H伸缩强度为0.05,比新米谷蛋白对应强度0.02显著增大,表明分子间结合程度升高,谷蛋白与淀粉分子结合更加紧密。除了酪氨酸的Fermi共振、1 333和1 152 cm-1处砜的吸收峰不高外,陈化谷蛋白的其余拉曼强度均高于陈米谷蛋白,说明陈化谷蛋白的氧化程度更高。红外光谱表明,陈米谷蛋白和陈化谷蛋白中1 153,1 078和1 026 cm-1处的硫氧化物吸收峰增大,进一步支持谷蛋白发生了氧化。与新米谷蛋白相比,陈米谷蛋白的溶解性、持水性、乳化性和乳化稳定性均显著降低,而持油性升高,支持陈米中谷蛋白发生了明显氧化。陈化谷蛋白的溶解性（除pH 9）、持水性和乳化性比陈米谷蛋白更低,持油性更高,表明新米谷蛋白被提取出来后单独陈化时氧化程度更深。陈化后谷蛋白功能性质的变化支持红外和拉曼光谱显示的氧化变化,这为阐明蛋白质在陈米品质劣变中的作用提供了光谱依据,为控制稻米陈化劣变以减少产后损失奠定基础。     

Synaptic Plasticity and Spike Synchronisation in Neuronal Networks

Brain plasticity, also known as neuroplasticity, is a fundamental mechanism of neuronal adaptation in response to changes in the environment or due to brain injury. In this review, we show our results about the effects of synaptic plasticity on neuronal networks composed by Hodgkin-Huxley neurons. We show that the final topology of the evolved network depends crucially on the ratio between the strengths of the inhibitory and excitatory synapses. Excitation of the same order of inhibition revels an evolved network that presents the rich-club phenomenon, well known to exist in the brain. For initial networks with considerably larger inhibitory strengths, we observe the emergence of a complex evolved topology, where neurons sparsely connected to other neurons, also a typical topology of the brain. The presence of noise enhances the strength of both types of synapses, but if the initial network has synapses of both natures with similar strengths. Finally, we show how the synchronous behaviour of the evolved network will reflect its evolved topology.     

Delay-induced intermittent transition of synchronization in neuronal networks with hybrid synapses

We study the dependence of synchronization transitions in scale-free networks of bursting neurons with hybrid synapses on the information transmission delay and the probability of inhibitory synapses. It is shown that, irrespective of the probability of inhibitory synapses, the delay always plays a subtle role during synchronization transition of the scale-free neuronal networks. In particular, regions of irregular and regular propagating excitatory fronts appear intermittently as the delay increases. These delay-induced synchronization transitions are manifested as well-expressed minima in the measure for spatiotemporal synchrony. In addition, it is found that, for smaller and larger probability of inhibitory synapses, intermittent synchronization transition is relatively profound, while for the moderate probability of inhibitory synapses, synchronization transition seems less profound. More interestingly, it is found that as the probability of inhibitory synapses is large, regions of synchronization are upscattering.     

基于二维材料MXene的仿神经突触忆阻器的制备和长/短时程突触可塑性的实现

兼具长时程可塑性与短时程可塑性的电子突触被认为是类脑计算系统的重要基础.将一种新型二维材料MXene应用到忆阻器中,制备了基于Cu/MXene/SiO_2/W的仿神经突触忆阻器.结果表明, Cu/MXene/SiO_2/W忆阻器成功实现了稳定的双极性模拟阻态切换,同时成功模拟了生物突触短时程可塑性的双脉冲易化功能和长时程可塑性的长期增强/抑制行为,其中双脉冲易化的易化指数与脉冲间隔时间相关. Cu/MXene/SiO_2/W忆阻器的突触仿生特性,归功于MXene辅助的Cu离子电导丝形成与破灭的类突触响应机理.由于Cu/MXene/SiO_2/W忆阻器兼具长时程可塑性与短时程可塑性,其在突触仿生电子学和类脑智能领域将会具有巨大的应用前景.     

Nonlinear neural networks. I. General theory

A neural network is called nonlinear if the introduction of new data into the synaptic efficacies has to be performed through anonlinear operation. The original Hopfield model is linear, whereas, for instance, clipped synapses constitute a nonlinear model. Here a general theory is presented to obtain the statistical mechanics of a neural network with finitely many patterns and arbitrary (symmetric) nonlinearity. The problem is reduced to minimizing a free energy functional over all solutions of a fixed-point equation with synaptic kernelQ. The case of clipped synapses with bimodal and Gaussian probability distribution is analyzed in detail. To this end, a simple theory is developed that gives the spectrum ofQ and thereby all the solutions that bifurcate from the high-temperature phase.     

Cubic distortion product otoacoustic emissions in young and aged chinchillas exposed to low-frequency noise.

The aim of this study was to examine susceptibility to noise-induced hearing loss in animals with and without age-related hearing loss (AHL), using cubic distortion product otoacoustic emissions (CDPs) to assess the functional status of the outer hair cell (OHC) system. Subjects were young (< or = 3-yr-old) and aged (10- to 15-yr-old) chinchillas. CDP thresholds and input/output (I/O) functions were measured before and after exposure to 95 dB or 106 dB SPL low-frequency noise. The results indicate that (a) aging in the chinchilla is associated with significant elevations of CDP thresholds and depression of CDP I/O functions, (b) noise exposures cause equivalent CDP threshold elevations and amplitude reductions in young animals with normal hearing and older animals with AHL, and (c) CDP threshold and amplitude measures provide information that complements evoked potentials measured from the auditory midbrain.     

Synaptic input statistics tune the variability and reproducibility of neuronal responses

Synaptic waveforms, constructed from excitatory and inhibitory presynaptic Poisson trains, are presented to living and computational neurons. We review how the average output of a neuron (e.g., the firing rate) is set by the difference between excitatory and inhibitory event rates while neuronal variability is set by their sum. We distinguish neuronal variability from reproducibility. Variability quantifies how much an output measure is expected to vary; for example, the interspike interval coefficient of variation quantifies the typical range of interspike intervals. Reproducibility quantifies the similarity of neuronal outputs in response to repeated presentations of identical stimuli. Although variability and reproducibility are conceptually distinct, we show that, for ideal current source synapses, reproducibility is defined entirely by variability. For physiologically realistic conductance-based synapses, however, reproducibility is distinct from variability and average output, set by the Poisson rate and the degree of synchrony within the synaptic waveform.     

New Insights into the Effects of Physical Aging on Glass Transition of Polystyrene by FTIR

A new method to detect the glass transition was used to investigate the effects of physical aging on the glass transition of polystyrene by Fourier transform infrared (FTIR) spectroscopy. The results showed that the onset point of the glass transition shifted to higher temperature with aging, but the end point didn't change. It was demonstrated that this method was of great use in determining the glass transition temperature of aged polymeric samples. For each aged sample, the four bands assigned to the vibrational modes of the main chain groups and the side groups of polystyrene showed the same transition regions, indicating that the main chain and the side groups were aging synchronously. The rates of increase of the relative peak areas for the four investigated bands during the glass transition decreased with aging with the increased rates of the relative peak areas for the two bands assigned to side group decreasing less than those of main chain, which seemed to indicate the dominance of the side group in aging process.     

The influence of connectivity on the firing rate in a neuronal network with electrical and chemical synapses

We study the firing rate properties of a cellular automaton model for a neuronal network with chemical synapses. We propose a simple mechanism in which the nonlocal connections are included, through electrical and chemical synapses. In the latter case, we introduce a time delay which produces self-sustained activity. Nonlocal connections, or shortcuts, are randomly introduced according to a specified connection probability. There is a range of connection probabilities for which neuron firing occurs, as well as a critical probability for which the firing ceases in the absence of time delay. The critical probability for nonlocal shortcuts depends on the network size according to a power-law. We also compute the firing rate amplification factor by varying both the connection probability and the time delay for different network sizes.