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Molecular and Anatomical Dissection of Olfactory neural circuits Using Transsynaptic PRV Tracers

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Molecular and Anatomical Dissection of Olfactory Neural Circ...

In vitro spatiotemporal imaging of biophotonic activities and transmission in neural circuits

中国神经科学学会第十二届全国学术会议

作者： Zhonghua Lu The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences

neural circuits mediating innate behavioral and physiological responses possess both molecular and anatomical features that ensure functional specificity towards distinct stimuli. Using newly developed retrograde monosynaptic-and polysynapticPseudorabies virus（PRV） tracers, we have searched for both molecular and anatomical characteristics of olfactory neural circuits that mediate innate reproductive or fear responses. We found small subsets of Olfactory Receptors（ORs） that send input to hypothalamic neurons controlling reproductive hormones. These receptors detect both pheromones and predator odors and may contribute to hormonal changes towards distinct chemical cues. Transsynaptic tracing from CRH neurons with PRV tracers identified a key area in the olfactory cortex that transmit predator odor information to mediate stress hormone reactions to predators.

关键词： neural circuits tracing PRV tracer circuit mapping

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In vitro spatiotemporal imaging of biophotonic activities an...

Multimodal Nature of the Single-cell Primate Brain Atlas: Morphology, Transcriptome, Electrophysiology, and Connectivity

中国神经科学学会第十届全国学术会议

作者： Rendong TANG Jiapei DAI Wuhan Institute for Neuroscience and Neuroengineering South-Central University for Nationalities

Objective The processing of neural information in neural circuits plays a key role in neural functions.It is well accepted that neuronal communication is mediated by bioelectricity and chemical molecules via the processes called bioelectrical and chemical transmission,respectively,which mainly occur in axons and synapses.Indeed,they seem to provide reasonable explanations for the basic functions and neural encoding of the nervous system,but many unanswered questions and debates remain.It has recently been suggested that biophotons,also called ultra-weak photon emissions,may play a potential role in neural signal transmission,contributing to the understanding of the high functions of nervous system;however,the experimental analysis of biophotonic activities(emissions) in neural circuits has been hampered due to technical limitations.Methods By developing and optimizing an in vitro biophoton imaging method,we characterize the glutamate-induced biophotonic activities along the axons of cortical projection neurons and in the intrahippocampal circuits in mouse brain slices.Results We show that the long-lasting application of 50 mM glutamate to brain slices produces a gradual and significant increase of biophotonic activities and achieves the maximal effect within approximately 90 min,which then lasts for a relatively long time(> 200 min).The initiation and/or maintenance of biophotonic activities by glutamate can be obviously blocked by oxygen and glucose deprivation,together with the application of a cytochrome c oxidase inhibitor(sodium azide),but only partly by an action potential inhibitor(TTX),an anesthetic(procaine),or the removal of intracellular and extracellular Ca.The detected biophotonic activities mostly originate from axons,and the hyperphospholyation of microtubule-associated protein tau leads to a significant decrease of biophotonic activities in axons.Furthermore,the application of glutamate in the hippocampal dentate gyrus results in obvious biophotonic activities in its intrahippocampal projection ar

关键词： neural circuits biophotons biophotonic transmission ultra-weak photon emission imaging system glutamate microtubule

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NEUROSCIENCE BULLETIN 2024年第4期40卷 517-532页

作者： Shen, Yuhui Shao, Mingting Hao, Zhao-Zhe Huang, Mengyao Xu, Nana Liu, Sheng Sun Yat Sen Univ Zhongshan Ophthalm Ctr State Key Lab Ophthalmol Guangdong Prov Key Lab Ophthalmol & Visual Sci Guangzhou 510060 Peoples R China Guangdong Prov Key Lab Brain Funct & Dis Guangzhou 510080 Peoples R China

Primates exhibit complex brain structures that augment cognitive function. The neocortex fulfills high-cognitive functions through billions of connected neurons. These neurons have distinct transcriptomic, morphological, and electrophysiological properties, and their connectivity principles vary. These features endow the primate brain atlas with a multimodal nature. The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex, enabling a multimodal neuronal atlas to be established in great detail: (1) single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references, covering all major transcriptomic cell types; (2) patch-seq links the morphological and electrophysiological features to the transcriptomic reference; (3) multicell patch-clamp delineates the principles of local connectivity. Here, we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate RNA-SEQ ALZHEIMERS-DISEASE PYRAMIDAL NEURONS SYNAPTIC CONNECTIONS MOLECULAR DIVERSITY INHIBITORY NEURONS PREFRONTAL CORTEX neural circuits MOUSE NEOCORTEX

Whole-brain Optical Imaging:A Powerful Tool for Precise Brain Mapping at the Mesoscopic Level

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Neuroscience Bulletin 2023年第12期39卷 1840-1858页

作者： Tao Jiang Hui Gong Jing Yuan Huazhong University of Science and Technology-Suzhou Institute for Brainsmatics Jiangsu Industrial Technology Research InstituteSuzhou215123China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan430074China

The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons.Precise dissection of neural circuits at the mesoscopic level can provide important structural information for understanding the brain.Optical approaches can achieve submicron lateral resolution and achieve“optical sectioning”by a variety of means,which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level.Automated whole-brain optical imaging methods based on tissue clearing or histological sectioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural information in a large volume of tissues.Combined with various fluorescent labeling techniques,whole-brain optical imaging methods have shown great potential in the brain-wide quantitative profiling of cells,circuits,and blood vessels.In this review,we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.

关键词： Whole-brain optical imaging Optical sectioning Micrometer resolution Brain connectome neural circuits Neuron

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 diseases.Recombinant 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 inputs.Although 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 vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our 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 recombination.These 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

维普期刊数据库

Prefrontal cortical circuits in anxiety and fear:an overview

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Frontiers of Medicine 2022年第4期16卷 518-539页

作者： Yihua Chen Nengyuan Hu Jianming Yang Tianming Gao State Key Laboratory of Organ Failure Research Key Laboratory of Mental Health of the Ministry of EducationGuangdong−Hong Kong−Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangdong Province Key Laboratory of Psychiatric DisordersDepartment of NeurobiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Pathological anxiety is among the most difficult neuropsychiatric diseases to treat pharmacologically,and it represents a major societal problem.Studies have implicated structural changes within the prefrontal cortex(PFC)and functional changes in the communication of the PFC with distal brain structures in anxiety disorders.Treatments that affect the activity of the PFC,including cognitive therapies and transcranial magnetic stimulation,reverse anxiety-and fear-associated circuit abnormalities through mechanisms that remain largely unclear.While the subjective experience of a rodent cannot be precisely determined,rodent models hold great promise in dissecting well-conserved circuits.Newly developed genetic and viral tools and optogenetic and chemogenetic techniques have revealed the intricacies of neural circuits underlying anxiety and fear by allowing direct examination of hypotheses drawn from existing psychological concepts.This review focuses on studies that have used these circuit-based approaches to gain a more detailed,more comprehensive,and more integrated view on how the PFC governs anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide a roadmap for the future development of therapies for pathological anxiety.

关键词： prefrontal cortex anxiety fear neural circuits optogenetics DREADD

A Brief Summary of Current Therapeutic Strategies for Spinal Cord Injury

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Engineering 2022年第6期8卷 46-52页

作者： Chun Yao Xin Tang Yuqi Cao Xuhua Wang Bin Yu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education&NMPA Key Laboratory for the Research and Evaluation of Tissue Engineering Technology Products Co-Innovation Center of NeuroregenerationNantong UniversityNantong 226001China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Science and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310003China Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China

Spinal cord injury(SCI)is a tremendous disaster in a person’s life.It interrupts the brain-body neuronal circuits,resulting in functional deficits.Pathogenesis of SCI is a progressive and comprehensive event.In clinical trials,attempts to promote nerve regeneration and functional recovery after SCI have met with failures.Recently,with the development of transcriptome sequencing and biomaterials,researchers have struggled to explore novel efficient therapeutic treatments for SCI.Here,we summarize the recent pro-gress that has been made in SCI repair based on the lesion microenvironment,neural circuits,and bioma-terial scaffolds.We also propose several important directions for future research,including targeted-microRNA therapy,blood vessel interventions,and multiple treatment combinations.In short,we hope this review will enlighten researchers in the field and pave the way for SCI therapy.

关键词： Spinal cord injury Microenvironment neural circuits Biomaterial scaffolds

维普期刊数据库

Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+neurons.These Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

Neuroimmune crosstalk through brain-derived neurotrophic factor and its precursor pro-BDNF: New insights into mood disorders

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World Journal of Psychiatry 2022年第3期12卷 379-392页

作者： Xiao-Pei Zhao Hui Li Ru-Ping Dai Department of Anesthesiology The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.

关键词： Brain-derived neurotrophic factor pro-BDNF neural circuits Neuroimmune Mood disorders Depression