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.     

忆阻器在神经突触仿生中的应用研究进展

随着对计算机性能要求的不断提高,人们一直在寻找能像人脑一样具有学习记忆功能的新型计算机。自从2008年惠普实验室发现忆阻器以后,发展具有人脑水平的智能计算机成为可能。众所周知,突触是大脑神经网络的基本单元,突触可塑性是学习和记忆的生物学基础。因此,为了实现具有学习和记忆功能的智能计算机,利用忆阻器模拟突触可塑性至关重要。综述了忆阻器在模拟突触的增强、抑制、短时程可塑性和长时程可塑性方面的研究现状,并对其研究前景进行了展望。     

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

Metformin is a first-line drug for treating type 2 diabetes mellitus (T2DM) and one of the most commonly prescribed drugs in the world. Besides its hypoglycemic effects, metformin also can improve cognitive or mood functions in some T2DM patients; moreover, it has been reported that metformin exerts beneficial effects on many neurological disorders, including major depressive disorder (MDD), Alzheimer’s disease (AD) and Fragile X syndrome (FXS); however, the mechanism underlying metformin in the brain is not fully understood. Neurotransmission between neurons is fundamental for brain functions, and its defects have been implicated in many neurological disorders. Recent studies suggest that metformin appears not only to regulate synaptic transmission or plasticity in pathological conditions but also to regulate the balance of excitation and inhibition (E/I balance) in neural networks. In this review, we focused on and reviewed the roles of metformin in brain functions and related neurological disorders, which would give us a deeper understanding of the actions of metformin in the brain.     

类脑计算新发展——“TrueNorth”神经元芯片

类脑计算是一种基于神经网络的全新数据存储和计算技术,通过模拟大脑的工作机理,可以突破传统计算机处理大型问题时遇到的冯·诺依曼瓶颈,在显著提高信息处理速度的同时大幅降低功耗,并且具有自我学习和自适应能力。介绍了IBM最新研究的TrueNorth神经元芯片技术,包括其基本架构、工作原理、芯片性能、应用成果等,并展望了类脑计算技术的未来发展前景。     

Eliminating Synaptic Ribbons from Rods and Cones Halves the Releasable Vesicle Pool and Slows Down Replenishment

Glutamate release from rod and cone photoreceptor cells involves presynaptic ribbons composed largely of the protein RIBEYE. To examine roles of ribbons in rods and cones, we studied mice in which GCamP3 replaced the B-domain of RIBEYE. We discovered that ribbons were absent from rods and cones of both knock-in mice possessing GCamP3 and conditional RIBEYE knockout mice. The mice lacking ribbons showed reduced temporal resolution and contrast sensitivity assessed with optomotor reflexes. ERG recordings showed 50% reduction in scotopic and photopic b-waves. The readily releasable pool (RRP) of vesicles in rods and cones measured using glutamate transporter anion currents (I_A(glu)) was also halved. We also studied the release from cones by stimulating them optogenetically with ChannelRhodopsin2 (ChR2) while recording postsynaptic currents in horizontal cells. Recovery of the release from paired pulse depression was twofold slower in the rods and cones lacking ribbons. The release from rods at −40 mV in darkness involves regularly spaced multivesicular fusion events. While the regular pattern of release remained in the rods lacking ribbons, the number of vesicles comprising each multivesicular event was halved. Our results support conclusions that synaptic ribbons in rods and cones expand the RRP, speed up vesicle replenishment, and augment some forms of multivesicular release. Slower replenishment and a smaller RRP in photoreceptors lacking ribbons may contribute to diminished temporal frequency responses and weaker contrast sensitivity.     

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。