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In vivo fiber photometry of neural activity in response to optogenetically manipulated inputs in freely moving mice

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Journal of Innovative Optical Health Sciences 2017年第5期10卷 47-58页

作者： Liang Li Yajie Tang Leqiang Sun Khaista Rahman Kai Huang Weize Xu Jinsong Yu Jinxia Dai Gang Cao State Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan 430070 P.R.China College of Veterinary Medicine Huazhong Agricultural University Wuhan 430070 P.R.China Bio-Medical center Huazhong Agricultural University Wuhan 430070 P.R.China Key Laboratory of Development of Veterinary Diagnostic Products Ministry of Agriculture College of Veterinary Medicine Huazhong Agricultural UniversityWuhan 430070P.R.China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074P.R.China Convergence Technology Co.Ltd 1037 Luoyu Road Hongshan DistrictWuhan 430074P.R.China

In vito fber photometry is a powerful technique to analyze the dy namics of population neurons during fiunctional study of ***,we introduced a detailed protocol for fiber photometry-based calciun reording in freely moving mice,covering from virus injection,fiber stub insertion,optogenetical stimulation to data procurement and ***,we applied this protocol to explore neuronal activity of mice latenal-posterior(LP)thalaric nucleus in response to optogenetical stimulation of primary visual cortex(V1)neurons,and explore axon clusters activity of optogenetically evoked V1 *** confirmation of virus-based protein expression in V1 and precise fber insertion indicated that the surgery procedure of this protocol is reliable for functional calcium *** scripts for data analysis and some tips in our protocol are provided in ***,this protocol is simple,low-cost,and effective for neuronal activity detection by fiber photometry,which will hep neuroscience researchers to carry out fiunctional and behavioral study in vivo.

关键词： Fiber photometry surgical operation optogenetical stimulation neural activity freely moving recording

Influences of NR2B-containing NMDA Receptors Knockdown on neural activity in Hippocampal Newborn Neurons

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第4期33卷 457-462页

作者：李志军张慧文唐娜 Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Function Examination The Second Affiliated HospitalNanhua University

Summary： Adult-bom neurons undergo a transient period of plasticity during their integration into the neural circuit. This transient plasticity may involve NMDA receptors containing NR2B, the major sub unit expressed at early developmental stages. The main objective of the present study was to investigate the effects of NR2B gene knockdown on the functional integration of the adult-born granule cells gen- erated from the subgranule zone （SGZ） in the hippocampus. The small interfering RNA （siRNA） was used to knock down the NR2B gene in the adult-born hippocampal neurons. In the functional integration test, the mice were exposed to a novel environment （open field arena）, and the expression of c-fos was immunohistochemically detected in the hippocampus. After exposure to the novel environment, siRNA-NR2B mice were significantly different from control mice in either the number of squares or the number of rears they crossed, showing decreased horizontal and vertical activity （P〈0.05）. Moreover, the c-fos expression was increased in both control and siRNA-NR2B mice after open field test. But, it was significantly lower in siRNA-NR2B neurons than in control neurons. It was concluded that the neu- ral activity of newborn neurons is regulated by their own NR2B-containing NMDA glutamate receptors during a short, critical period after neuronal birth.

关键词： adult neurogenesis NR2B-containing NMDA receptors neural activity RNA interference

Genetically encoded neural activity indicators

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Translational Neuroscience and Clinics 2018年第1期4卷 1-15页

作者： Fang Luo Yin Wei Ziyue Wang Minmin Luo Ji Hu School of Life Science and Technology ShanghaiTech University National Institute of Biological Sciences

Recent years have witnessed the fascinating development of imaging approaches to studying neural activities; this progress has been based on an influx of ideas and methods from molecular biology and optical engineering. Here we review the design and application of genetically encoded indicators for calcium ions, membrane potential and neurotransmitters. We also summarize common strategies for the design and optimization of genetically encoded neural activity indicators.

关键词： calcium imaging neural activity membrane potential probe neurotransmitter reporter

Brief electrical nerve stimulation enhances intrinsic repair capacity of the focally demyelinated central nervous system

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neural Regeneration Research 2022年第5期17卷 1042-1050页

作者： Lydia Ayanwuyi Nataliya Tokarska Nikki A.McLean Jayne M.Johnston Valerie M.K.Verge Department of Anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research Center University of SaskatchewanSaskatoonSKCanada

Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair *** this same potential exists in the central nervous system is not ***,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated *** reveal a robust focal demyelination at 7 days post-LPC *** of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of *** also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon *** these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple *** animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).

关键词： axon protection demyelination immune response lysophosphatidyl choline macrophage microglia multiple sclerosis myelin nervous system repair neural activity polarization

Engineering human spinal microphysiological systems to model opioid-induced tolerance

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Bioactive Materials 2023年第4期22卷 482-490页

作者： Hongwei Cai Zheng Ao Chunhui Tian Zhuhao Wu Connor Kaurich Zi Chen Mingxia Gu Andrea G.Hohmann Ken Mackie Feng Guo Department of Intelligent Systems Engineering Indiana UniversityBloomingtonIN47405United States Department of Surgery Brigham and Women’s Hospital/Harvard Medical SchoolBostonMA02115United States Division of Pulmonary Biology Center for Stem Cell and Organoid Medicine(CuSTOM)Cincinnati Children’s Hospital Medical CenterCincinnatiOH45229United States University of Cincinnati School of Medicine CincinnatiOH45229United States Gill Center for Biomolecular Science and Department of Psychological and Brain SciencesIndiana UniversityBloomingtonIN47405United States

pioids are commonly used for treating chronic ***,with continued use,they may induce tolerance and/or hyperalgesia,which limits therapeutic *** human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied,in part,because current models cannot fully recapitulate human ***,we engineered novel human spinal microphysiological systems(MPSs)integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced *** spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity *** found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids,but also promotes their neuron maturation,neural activity,and functional *** further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia,as measured by altered neural activity,and downregulation ofμ-opioid receptor expression of human spinal *** MPSs are scalable,cost-effective,easy-to-use,and compatible with commonly-used well-plates,thus allowing plug-and-play measurements of neural *** believe the MPSs hold a promising translational potential for studying human pain etiology,screening new treatments,and validating novel therapeutics for human pain medicine.

关键词： Microphysiological systems Organ-on-chip In-situ electrical sensing Spinal cord organoids Opioid-induced tolerance and hyperalgesia neural activity

neural Integration of Audiovisual Sensory Inputs in Macaque Amygdala and Adjacent Regions

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Neuroscience Bulletin 2023年第12期39卷 1749-1761页

作者： Liang Shan Liu Yuan Bo Zhang Jian Ma Xiao Xu Fei Gu Yi Jiang Ji Dai CAS Key Laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions Shenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Brain and Cognitive Science CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China Chinese Institute for Brain Research Beijing 102206China Shenzhen Technological Research Center for Primate Translational Medicine Shenzhen 518055China Key Laboratory of Brain Science Zunyi Medical UniversityZunyi563000China

Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the *** regions such as the amygdala are involved in sensory processing including vision and audition,yet their roles in multisensory integration remain *** this study,we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual *** a sample of 332 neurons,we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation,which could be classified into four types with differentiated regional *** the hierarchical clustering method,neurons were further clustered into five groups and associated with different integrating functions and ***,regions distinguishing congruent and incongruent bimodal sensory inputs were ***,visual processing dominates audiovisual integration in the amygdala and adjacent *** findings shed new light on the neural mechanisms of multisensory integration in the primate brain.

关键词： Macaque Amygdala-Multisensory Audiovisual integration neural activity Multichannel recording

A rabies virus-based toolkit for efficient retrograde labeling and monosynaptic tracing

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neural Regeneration Research 2023年第8期18卷 1827-1833页

作者： Kun-Zhang Lin Lei Li Wen-Yu Ma Xin Yang Zeng-Peng Han Neng-Song Luo Jie Wang Fu-Qiang Xu The Brain Cognition and Brain Disease Institute(BCBDI) Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhenKey Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhenGuangdong ProvinceChina State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhanHubei ProvinceChina University of Chinese Academy of Sciences BeijingChina Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei ProvinceChina Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions ShenzhenGuangdong ProvinceChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina

Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain *** rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic *** several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these *** overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG *** results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene *** findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.

关键词： functional studies neural activity neural circuits projection neurons rAAV9-Retro rabies virus recombination retrograde labeling synaptic inputs trans-monosynaptic tracing

Epidural electrical stimulation for spinal cord injury

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neural Regeneration Research 2021年第12期16卷 2367-2375页

作者： Elliot H.Choi Sandra Gattas Nolan J.Brown John D.Hong Joshua N.Limbo Alvin Y.Chan Michael Y.Oh Department of Pharmacology School of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Ophthalmology Gavin Herbert Eye InstituteSchool of MedicineUniversity of CaliforniaIrvineCAUSA Department of Neurosurgery University of CaliforniaIrvineCAUSA

A long-standing goal of spinal cord injury research is to develop effective repair strategies,which can restore motor and sensory functions to near-normal *** advances in clinical management of spinal cord injury have significantly improved the prognosis,survival rate and quality of life in patients with spinal cord *** addition,a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord *** efforts enabled the development of pharmacologic agents,biomaterials and stem-cell based *** these efforts,there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal *** challenges led to an increased focus on another therapeutic approach,namely *** multiple animal models of spinal cord injury,epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor *** evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord ***,most clinical studies were conducted on a very small number of patients with a wide range of spinal cord ***,subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation ***,we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord *** also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

关键词： central nervous system chondroitin sulfate proteoglycans epidural electrical stimulation glial scar gliosis neural activity neuromodulation oligodendrocyte spinal cord injury

INTRINSIC OPTICAL SIGNAL IMAGING OF RETINAL activity IN FROG EYE

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Journal of Innovative Optical Health Sciences 2009年第2期2卷 201-208页

作者： XIN-CHENG YAO LEI LIU YANG-GUO LI Department of Biomedical Engineering University of Alabama at Birmingham Birmingham AL 35294USA Department of Optometry University of Alabama at Birmingham Birmingham AL 35294USA

Using a near-infrared(NIR)light flood-illumination imager equipped with a high-speed(120 Hz)CCD camera,we demonstrated optical imaging of stimulus-evoked retinal activity in isolated,but intact,frog *** fast and slow transient intrinsic optical signals(IOSs)were *** optical response occurred immediately after the stimulus onset,could reach peak magnitude within 100 ms,and correlated tightly with ON and OFF edges of the visible light stimulus;while slow optical response lasted a relatively long time(many seconds).High-resolution images revealed both positive(increasing)and negative(decreasing)IOSs,and dynamic optical change at individual CCD pixels could often exceed 10%of the background light *** experiment on isolated eye suggests that further development of fast,high(sub-cellular)resolution fundus imager will allow robust detection of fast IOSs in vivo,and thus allow noninvasive,three-dimensional evaluation of retinal neural function.

关键词： Near-infrared light imaging neural activity retina visual information processing retinal diagnosis.