Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors

The γ-aminobutyric acid type A receptor (GABA_AR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABA_AR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABA_ARs and D5Rs form dynamic surface clusters. Disrupting the GABA_AR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABA_ARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABA_ARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABA_AR and D5R, and uncover a non-canonical role in regulating synaptic transmission.     

Ion Channels and Electroosmosis in Porous Geopolymers: A Novel Category of Low-Cost Memristors

Memristors are electric components that emulate the memory and computational properties of biological synapses by remembering the current that flows through them. Here, for the first time, the memristive properties of geopolymers, inexpensive ceramic materials manufactured at room temperature from alkaline activation of amorphous aluminosilicate precursors, are presented. It is demonstrated that geopolymers present all the fingerprints of memristors, and a physics-based model is proposed, which demonstrates that electroosmosis in the bulk geopolymer pores induces ion channels that foster change in the overall conductance of the bulk material, contributing to the observed memristive behavior. This model opens the door to a new category of porous electroosmosis-based bulk memristors. Synaptic functions such as short-term plasticity and long-term plasticity, as well as endurance and retention capabilities are also demonstrated. The reported findings pave the way to the use of geopolymers for low-cost applications in neuromorphic computing.     

Low voltage and time constant organic synapse-transistor

We report on an artificial synapse, an organic synapse-transistor (synapstor) working at 1 V and with a typical response time in the range 100–200 ms. This device (also called NOMFET, Nanoparticle Organic Memory Field Effect Transistor) combines a memory and a transistor effect in a single device. We demonstrate that short-term plasticity (STP), a typical synaptic behavior, is observed when stimulating the device with input spikes of 1 V. Both significant facilitating and depressing behaviors of this artificial synapse are observed with a relative amplitude of about 50% and a dynamic response <200 ms. From a series of in-situ experiments, i.e. measuring the current–voltage characteristic curves in-situ and in real time, during the growth of the pentacene over a network of gold nanoparticles, we elucidate these results by analyzing the relationship between the organic film morphology and the transport properties. This synapstor works at a low energy of about 2 nJ/spike. We discuss the implications of these results for the development of neuro-inspired computing architectures and interfacing with biological neurons.     

Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.     

模拟神经网络VLSI脉冲流技术在故障诊断中的应用分析

介绍了模拟神经网络VLSI脉冲流技术实现神经网络模式识别硬件电路的方法，并且直接将故障分类。提出利用包含有故障信息的原始模拟噪声信号，经过前置信号处理和神经网络运算，得出VLSI电路输出端电容的电压值－代表待识别信号与模板故障信号的“欧氏距离”，以实现噪声故障信号的实时硬件在线识别。     

Advances in Design and Application of Spiking Neural Networks

This paper presents new findings in the design and application of biologically plausible neural networks based on spiking neuron models, which represent a more plausible model of real biological neurons where time is considered as an important feature for information encoding and processing in the brain. The design approach consists of an evolutionary strategy based supervised training algorithm, newly developed by the authors, and the use of different biologically plausible neuronal models. A dynamic synapse (DS) based neuron model, a biologically more detailed model, and the spike response model (SRM) are investigated in order to demonstrate the efficacy of the proposed approach and to further our understanding of the computing capabilities of the nervous system. Unlike the conventional synapse, represented as a static entity with a fixed weight, employed in conventional and SRM-based neural networks, a DS is weightless and its strength changes upon the arrival of incoming input spikes. Therefore its efficacy depends on the temporal structure of the impinging spike trains. In the proposed approach, the training of the network free parameters is achieved using an evolutionary strategy where, instead of binary encoding, real values are used to encode the static and DS parameters which underlie the learning process. The results show that spiking neural networks based on both types of synapse are capable of learning non-linearly separable data by means of spatio-temporal encoding. Furthermore, a comparison of the obtained performance with classical neural networks (multi-layer perceptrons) is presented.     

Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis

Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these interactions in axon regeneration and synaptogenesis. For example, PTPσ, a member of type IIa RPTPs, on axon terminals is monomerized and activated by the extracellular CS deposited in neural injuries, dephosphorylates cortactin, disrupts autophagy flux, and consequently inhibits axon regeneration. In contrast, HS induces PTPσ oligomerization, suppresses PTPσ phosphatase activity, and promotes axon regeneration. PTPσ also serves as an organizer of excitatory synapses. PTPσ and neurexin bind one another on presynapses and further bind to postsynaptic leucine-rich repeat transmembrane protein 4 (LRRTM4). Neurexin is now known as a heparan sulfate proteoglycan (HSPG), and its HS is essential for the binding between these three molecules. Another HSPG, glypican 4, binds to presynaptic PTPσ and postsynaptic LRRTM4 in an HS-dependent manner. Type IIa RPTPs are also involved in the formation of excitatory and inhibitory synapses by heterophilic binding to a variety of postsynaptic partners. We also discuss the important issue of possible mechanisms coordinating axon extension and synapse formation.     

High-resolution imaging of the immunological synapse and T-cell receptor microclustering through microfabricated substrates

T-cell activation via antigen presentation is associated with the formation of a macromolecular membrane assembly termed the immunological synapse (IS). The genesis of the IS and the onset of juxtacrine signalling is characterized by the formation of cell membrane microclusters and the organization of such into segregated microdomains. A central zone rich in T-cell receptor (TCR)–major histocompatibility complex microclusters termed the central supramolecular activation cluster (cSMAC) forms the bullseye of this structure, while the cellular interface surrounding the cSMAC is characterized by regions enriched in adhesion and co-stimulatory molecules. In vitro, the study of dynamic TCR microcluster coalescence and IS genesis in T-cell populations is hampered by cell migration within the culture system and resolution constraints resulting from lateral cell–cell contact. Here, we detail a novel system describing the fabrication of micropit arrays designed to sequester single T-cell–antigen presenting cell (APC) conjugates and promote IS formation in the horizontal imaging plane for high-resolution studies of microcluster dynamics. We subsequently use this system to describe the formation of the cSMAC in T-cell populations and to investigate the morphology of the interfacial APC membrane.     

大鼠胼胝体中突触结构的电镜观察

关于胼胝体中突触的在存在及其结构特点未见报道。选用２生后一周未睁眼Ｗｉｓｔａｒ大鼠４０只，随机分为摘除右侧眼球、左侧眼球、双侧眼球及正常对照四组，各组１０只。经灌流、固定、分别在胼胝体膝部、干部及压部取材后，电镜下观察了胼胝体中突触的结构。结果如下：１．胼胝 大多为化学性突触。２．各组及同组胼胝体各部中突触的美元数不同。３．胼胝体中突触数受视觉的影响。最后就胼胝体中突触的机能意义进行了讨论。