Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, Na_V1.3 and Na_V1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels Na_V1.3 and Na_V1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of Na_V1.3 and Na_V1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.     

航空有源滤波器自适应谐波检测仿真研究

介绍了基于自适应滤波理论的谐波检测原理,分析了自适应神经元算法用于谐波检测的可行性,设计了基于自适应谐波检测的并联型航空混合有源滤波器,对滤波特性进行了仿真研究。结果表明,基于自适应滤波理论的谐波检测方法能够快速、精确地检测相电流谐波含量,在相电压波形发生畸变的情况下,也具有较好的自适应能力、快速补偿能力和跟踪性能。     

Glutamatergic Neurons Differentiated from Embryonic Stem Cells: An Investigation of Differentiation and Associated Diseases

Neurons that have been derived from various types of stem cells have recently undergone significant study due to their potential for use in various aspects of biomedicine. In particular, glutamatergic neurons differentiated from embryonic stem cells (ESCs) potentially have many applications in both basic research and regenerative medicine. This review summarized the literatures published thus far and focused on two areas related to these applications. Firstly, these neurons can be used to investigate neuronal signal transduction during differentiation and this means that the genes/proteins/markers involved in this process can be identified. In this way, the dynamic spatial and temporal changes associated with neuronal morphology can be investigated relatively easily. Such an in vitro system can also be used to study how neurons during neurogenesis integrate into normal tissue. At the same time, the integration, regulation and functions of extracellular matrix secretion, various molecular interactions, various ion channels, the neuronal microenvironment, etc., can be easily traced. Secondly, the disease-related aspects of ESC-derived glutamatergic neurons can also be studied and then applied therapeutically. In the future, greater efforts are needed to explore how ESC-differentiated glutamatergic neurons can be used as a neuronal model for the study of Alzheimer’s disease (AD) mechanistically, to identify possible therapeutic strategies for treating AD, including tissue replacement, and to screen for drugs that can be used to treat AD patients. With all of the modern technology that is available, translational medicine should begin to benefit patients soon.     

In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats

The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain–spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Neural network models

The remarkable processing capabilities of the nervous system must derive at least in part from the large numbers of neurons participating (roughly 10¹⁰), since the timescales involved are of the order of milliseconds, rather than the nanoseconds of modern computers. We summarise common features of the neural network models which attempt to capture this behaviour and describe the many levels of parallelism which they exhibit. A range of models has been implemented on the SIMD (ICL Distributed Array Processor) and MIMD (Meiko Computing Surface) hardware at Edinburgh. Examples include: (i) training algorithms in the context of the Hopfield net, with specific application to the storage of words and text with content-addressable memory; (ii) the back-propagation training algorithm for the multi-layer perception; (iii) image restoration with Hopfield and Tank analogue neurons, and (iv) the Durbin and Willshaw elastic net, as applied to the travelling salesman problem.     

Synaptic Suppression Triplet‐STDP Learning Rule Realized in Second‐Order Memristors

The synaptic weight modification depends not only on interval of the pre‐/postspike pairs according to spike‐timing dependent plasticity (classical pair‐STDP), but also on the timing of the preceding spike (triplet‐STDP). Triplet‐STDP reflects the unavoidable interaction of spike pairs in natural spike trains through the short‐term suppression effect of preceding spikes. Second‐order memristors with one state variable possessing short‐term dynamics work in a way similar to the biological system. In this work, the suppression triplet‐STDP learning rule is faithfully demonstrated by experiments and simulations using second‐order memristors. Furthermore, a leaky‐integrate‐and‐fire (LIF) neuron is simulated using a circuit constructed with second‐order memristors. Taking the advantage of the LIF neuron, various neuromimetic dynamic processes, including local graded potential leaking out, postsynaptic impulse generation and backpropagation, and synaptic weight modification according to the suppression triplet‐STDP rule, are realized. The realized weight‐dependent pair‐ and triplet‐STDP rules are clearly in line with findings in biology. The physically realized triplet‐STDP rule is powerful in developing direction and speed selectivity for complex pattern recognition and tracking tasks. These scalable artificial synapses and neurons realized in second‐order memristors can intrinsically capture the neuromimetic dynamic processes; they are the promising building blocks for constructing brain‐inspired computation systems.     

Multifunctional Hybrid Nanoparticles for Traceable Drug Delivery and Intracellular Microenvironment‐Controlled Multistage Drug‐Release in Neurons

Innovative nanoparticles hold promising potential for disease therapy as drug delivery systems. For brain‐disease therapy, a drug delivery system that can sustainably control drug‐release and monitor fluorescence of the drug cargos is highly desirable. In this study, a light‐traceable and intracellular microenvironment‐responsive drug delivery system was developed based on the combination of glutathione‐responsive autoflurescent nanogel, dendrimer‐like mesoporous silica nanoparticles, and gold nanoparticles. The resulting hybrid nanoparticles represent a new class of delivery system that can efficiently load, transport, and control multistage‐release of sulfydryl‐containing drugs into neurons, with light‐traceable monitoring for future brain‐disease therapy.     

Suspended Silicon Microphotodiodes for Electrochemical and Biological Applications

Local electric stimulation of tissues and cells has gained importance as therapeutic alternative in the treatment of many diseases. These alternatives aim to deliver a less invasively stimuli in liquid media, making imperative the development of versatile micro‐ and nanoscale solutions for wireless actuation. Here, a simple microfabrication process to produce suspended silicon microphotodiodes that can be activated by visible light to generate local photocurrents in their surrounding medium is presented. Electrical characterization using electrical probes confirms their diode behavior. To demonstrate their electrochemical performance, an indirect test is implemented in solution through photoelectrochemical reactions controlled by a white‐LED lamp. Furthermore, their effects on biological systems are observed in vitro using mouse primary neurons in which the suspended microphotodiodes are activated periodically with white‐LED lamp, bringing out observable morphological changes in neuronal processes. The results demonstrate a simplified and cost‐effective wireless tool for photovoltaic current generation in liquid media at the microscale.     

A Leaky‐Integrate‐and‐Fire Neuron Analog Realized with a Mott Insulator

During the last half century, the tremendous development of computers based on von Neumann architecture has led to the revolution of the information technology. However, von Neumann computers are outperformed by the mammal brain in numerous data‐processing applications such as pattern recognition and data mining. Neuromorphic engineering aims to mimic brain‐like behavior through the implementation of artificial neural networks based on the combination of a large number of artificial neurons massively interconnected by an even larger number of artificial synapses. In order to effectively implement artificial neural networks directly in hardware, it is mandatory to develop artificial neurons and synapses. A promising advance has been made in recent years with the introduction of the components called memristors that might implement synaptic functions. In contrast, the advances in artificial neurons have consisted in the implementation of silicon‐based circuits. However, so far, a single‐component artificial neuron that will bring an improvement comparable to what memristors have brought to synapses is still missing. Here, a simple two‐terminal device is introduced, which can implement the basic functions leaky integrate and fire of spiking neurons. Remarkably, it has been found that it is realized by the behavior of strongly correlated narrow‐gap Mott insulators subject to electric pulsing.