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Is the neocortex a novel reservoir for adult mammalian neurogenesis?

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Neural Regeneration Research 2011年第17期6卷 1334-1341页

作者： Mengqi Zhang Hui Wang Kun Xiong Clinical Medicine Eight-year Program Xiangya Medical School of Central South University Changsha 410013 Hunan Province China Department of Anatomy and Neurobiology -Xiangya Medical School of Central South University Changsha 410013 Hunan Province China

A novel population of cells expressing typical markers of immature neurons, such as doublecortin-positive cells, was recently identified. This population was predominantly located in layer II of the adult cerebral cortex of relatively large mammals. These cells appear to maintain an immature phenotype for a protracted time window, suggesting a lifelong role in cortical plasticity under normal physiological conditions, and possibly under pathological conditions as well. This review discusses recent evidence regarding the detailed features of these unique cells, including their distribution, morphology, fate, temporal and spatial origin, as well as their relevance and possible functions in various physiological and pathological conditions. In addition, we review studies that have produced conflicting results, possibly as a result of discrepancies in the methodology used to detect neurogenesis. In theory, the properties of these cells indicate that they might exert a significant impact on neocortical function, informing potential therapeutic strategies designed to induce endogenous neurogenesis in the treatment of neuropathological diseases.

关键词： adult neurogenesis corticogenesis doublecortin neuroplasticity neocortex neuralregeneration

Elimination of electrical synapse between sister excitatory neurons in early postnatal neocortex changes mice’s anxiety-related behavior

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Elimination of electrical synapse between sister excitatory ...

中国神经科学学会第十届全国学术会议

作者： Xin SU Jing-Jing CHEN Xiao-Yang LI Lin-Yun LIU Yong-Chun YU Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University

In the developing neocortex,sister excitatory neurons produced by radial glial cell migrate along the radial glial fiber to the pial surface,resulting in ontogenetic columnar *** recent work has shown that sister excitatory neurons preferentially form transient electrical synapse with each other at early postnatal *** electrical synapses,which are mainly composed by connexin26 and connexin43 regulate the subsequent formation of preferential chemical synapse and contribute to functional similarity between sister excitatory *** remains unclear whether eliminating electrical synapse between sister excitatory neurons in early postnatal neocortex would affect juvenile mice’s *** using Cre-Loxp system,we hypodermically inject tamoxifen at postnatal day 1（P1）to induce conditional knockout of connexin26/connexin43 in excitatory neurons at early postnatal *** with immunohistochemistry,in utero electroporation,multiple-electrode whole-cell recordings,single-cell reverse transcription PCR,western blot as well as series of behavioral test,we find elimination of electrical synapse between sister excitatory neurons in early postnatal neocortex changes mice’s anxiety-related *** results indicate transient electrical synapses in early postnatal neocortex have important role in individual development.

关键词： electrical synapse sister excitatory neuron neocortex anxiety-related behavior

Electrical coupling and neural circuit formation in the neocortex

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Electrical coupling and neural circuit formation in the neoc...

中国神经科学学会第十二届全国学术会议

作者： Yong-Chun Yu Institutes of Brain Science State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science Fudan University

Electrical coupling between neurons in the neocortex is developmentally regulated. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, I reports the evidence that electrical coupling functionally influences microcircuit assembly during development and animal behavior in adulthood. We found sister excitatory neurons in ontogenetic columns preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. Blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons. Moreover, conditional deletion of Connexin 26（CX26） in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces dendritic morphology and excitatory synapse development. More importantly, CX26-c KO mice exhibit increased anxiety-like behavior. Interestedly, we observe electrical coupling between neocortical interneurons plays a critical role in regulating chemical synapse development and precise formation of circuits. Together, electrical couplings among excitatory neurons or inhibitory neurons at early postnatal stages are a critical step for neocortical development and function.

关键词： Electrical coupling neural circuits development neocortex

Presence and characterization of intermediate GAB Aergic-neuron progenitors in the neocortex

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Presence and characterization of intermediate GAB Aergic-neu...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Nobuaki TAMAMAKI Department of Morphological Neural Science School of MedicineKumamoto UniversityKumamoto 860-8556Japan

＜正＞Objective In the embryonic neocortex,neural cells are generated in the inner-most layer of the pallium,the ventricular zone（VZ）,and express cell proliferation markers,while differentiated neurons accumulate in the outer layers and express neuronal ***,the nature of intermediate neuron progenitors is not ***,we show that the SVZ of the perinatal mouse neocortex contains intermediate GABAergic-neuron progenitors（IGNPs）,whose fate seems to be the neuronal *** GFP-positive cells in the SVZ of GAD67-GFP knock-in mice by immunostaining, single-cell RT-PCR,and single-cell microarray *** We found that a substantial number expressed both neuronal and cell-cycle *** neuronal markers included GAD67,MAP2,βⅢ-tubulin,and those for proliferating cells were Ki-67,PCNA,cyclin-D *** addition,genes involved in asymmetric cell division,such as Notch3,deltal, delta4,and Numb had present calls in the microarray *** the data indicated that the cell-cycle phases are not for apoptosis,but for cell ***,the GFP-positive cells incorporated BrdU and produced pairs of BrdU andβⅢ- tubulin double-positive cells in *** Taken together,these data indicate that IGNPs divide asymmetrically or symmetrically,and produce only cells of the neuronal lineage in the developing neocortex.

关键词： GABAergic neuron progenitor development neocortex mouse

The morphological development of layer 1 neurons in mouse neocortex

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The morphological development of layer 1 neurons in mouse ne...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xing-Hua YAO,Yong-Chun YU~* Institute of Neurobiology,Fudan University,Shanghai,200032,China

＜正＞Objective Layer 1 is the top layer of the cerebral cortex,which originates from the neocortical marginal zone（MZ）.Although recently studies showed that layer 1 mainly populated Cajal-Retzius（C-R） Cells and some types of interneuron,the developing morphological properties of layer 1 neurons remain incompletely *** 3-D model neurons reconstructed from neurobiotin-labeled neurons in the mouse neocortical layer 1,this study provides a detailed morphological analysis at early postnatal days（P） from P1 to *** quantification provides new insight into the potential value of the layer 1 neuron morphology for cortical information *** We micro-injected 4% neurobiotin into layer 1 neurons from P1 to P15 under the neocortical horizontal *** revealed neurobiotin with Cy3-streptavidin,we reconstructed the neurons and analyzed their morphological ***（1） For the interneuron, three developmental periods were revealed,which were characterized by distinct growing rates and properties of alterations in different *** P1 to P5,the interneurons had a few short dendrites with a low density of *** P6 to 8,the extending of dendritic branches and the densities of spines were significantly increased. After P9,almost all compartments of interneuron grew slow.（2） Typical C-R cells showed an ovoid soma,a thick stem dendrite originating from one pole of the soma and a long main axon originating always from the opposite pole of the *** types of C-R cells according the dendritic branches,bipolar and multi-polar,were observed during P1 to P7. After P8,the number of C-R cells was dramatically decreased.（3） Dye coupling is a frequent observation in the immature *** about 30%of the neurobiotin-labeled C-R cells dye coupling to a group of 2-20 neurons in layer 1 and 2-5 pyramidal neurons in layers 2-3 were observed.（4） At P15,we found two types of intemeuron in layer *** two third of the neurons look like

关键词： Layerl neocortex morphological development Cajal-Retzius cell interaeuron

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

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Neural Regeneration Research 2024年第2期19卷 246-254页

作者： Ningxin Wang Rong Wan Ke Tang Precise Genome Engineering Center School of Life SciencesGuangzhou UniversityGuangzhouGuangdong ProvinceChina

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal *** development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and *** processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural *** generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

关键词： autism spectrum disorders cognition differentiation excitatory circuits intellectual disability neocortex neurodevelopmental disorders projection neuron specification transcriptional regulation

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

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Neural Regeneration Research 2014年第3期9卷 318-328页

作者： Chunling Fan Mengqi Zhang Lei Shang Ngobe Akume Cynthia Zhi Li Zhenyu Yang Dan Chen Jufang Huang Kun Xiong Department of Anatomy and Neurobiology Central South University School of Basic Medical Sciences Grade 2006 Eight-year Medicine Doctor Program Central South University Xiangya School of Medicine Grade 2011 Six-year Medicine Program of International Student Central South University Xiangya School of Medicine Grade 2008 Eight-year Medicine Doctor Program Central South University Xiangya School of Medicine

Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine （a marker of cell prolifera- tion）, c-Fos （a marker of cell viability） and NeuN （a marker of mature neurons）. Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

关键词： nerve regeneration neurogenesis prefrontal cortex neocortex guinea pig doublecortinprotein cell proliferation neurons 5-bromodeoxyuridine NSFC grant neural regeneration

No DCX-positive neurogenesis in the cerebral cortex of the adult primate

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Neural Regeneration Research 2020年第7期15卷 1290-1299页

作者： Ruo-Xu Liu Jie Ma Bin Wang Tian Tian Ning Guo Shao-Jun Liu Institute of Military Cognition and Brain Sciences BeijingChina Department of Pharmacy Medical CollegeHuanghe S&T UniversityZhengzhouHenan ProvinceChina

Whether endogenous neurogenesis occurs in the adult cortex remains *** increasing number of reports suggest that doublecortin(DCX)-positive neurogenesis persists in the adult primate cortex,attracting enormous attention *** this study,different DCX antibodies were used together with NeuN antibodies in immunohistochemistry and western blot assays using adjacent cortical sections from adult *** adsorption,antigen binding,primary antibody omission and antibody-free experiments were used to assess specificity of the *** found either strong fluorescent signals,medium-weak intensity signals in some cells,weak signals in a few perikarya or near complete lack of labeling in adjacent cortical sections incubated with the various DCX *** putative DCX-positive cells in the cortex were also positive for NeuN,a specific marker of mature ***,further experiments showed that most of these signals were either the result of antibody cross reactivity,the non-specificity of secondary antibodies or tissue *** confirmed DCX-positive cells were detected in the adult macaque cortex by *** findings show that DCX-positive neurogenesis does not occur in the cerebral cortex of adult primates,and that false-positive signals(artefacts)are caused by antibody cross reactivity and *** experimental protocols were approved by the Institutional Animal Care and Use Committee of the Institute of Neuroscience,Beijing,China(approval ***-AMMS-2014-501).

关键词： adult neurogenesis antigen neutralization autofluorescence cross reaction cross reactivity doublecortin neocortex NeuN non-specificity primates tissue adsorption

Effects of three needling manipulations of the right-side Zusanli(ST 36) on brain using functional magnetic resonance imaging

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Journal of Traditional Chinese Medicine 2017年第3期37卷 298-307页

作者： Lu Fengyan Gao Junhong Wang Yuanyuan Dai Qiufu Bao Yan Hong Yang Zhang Guolei Xin Juanjuan Zhao Yuxue Wu Shuyang Chen Yuanyuan Li Xiaojiao Fang Jiliang Yu Xiaochun Department of Needling Manipulation Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences Department of medical imaging Guang An Men Hospital China Academy of Chinese Medical Sciences

OBJECTIVE: To investigate the effects on the brain using three needling manipulations(twirling, lifting-thrusting, and twirling plus lifting-thrusting)when the right-side Zusanli(ST 36) acupoint was stimulated with ***: Seventeen healthy subjects accepted three needling manipulations stimulating the right Zusanli(ST 36) over separate days. Functional magnetic resonance imaging was used to detect changes in the brain during the manipulations, and then the needling sensations were recorded using the MGH acupuncture sensation scale(MASS) after each scan. f MRI data were processed using Statistical Parametric Mapping 8 to analyze the positiveand negative activation in the brain induced by different acupuncture ***: The individual needling sensations showed no statistically significant differences among the three manipulations. However, the MASS index showed that lifting-thrusting > twirling plus lifting-thrusting > twirling. Lifting-thrusting activated left premotor cortex, left postcentral,right middle frontal gyrus, left inferior frontal gyrus,right lingual gyrus, left insula, right putamen, bilateral cingulate gyrus and right cerebellum; and deactivated bilateral hippocampus and left *** activated bilateral orbital middle frontal gyrus, left opercular and triangular inferior frontal gyrus, and right middle occipital gyrus; and deactivated bilateral precuneus, right amygdala, left anterior cingulate gyrus, right inferior temporal gyrus,right middle frontal gyrus, right supplementary motor gyrus, and left postcentral. Twirling plus lifting-thrusting activated bilateral postcentral, left inferior occipital gyrus, left insula, left thalamus, left cingulate gyrus, and right putamen; and deactivated right superior frontal gyrus, right superior parietal gyrus, right temporal gyrus, right middle occipital gyrus, right insula, and left lingual gyrus. Pairwise comparisons of the three manipulations showed that signals induced by lifti

关键词： Needling methods Point ST 36 (Zusan-li) Magnetic resonance imaging Limbic system neocortex