Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i （CX3CRI） signaling pathway. However, ...Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i （CX3CRI） signaling pathway. However, whether microglia can influence the maturation and dendritic growth of newborn neurons during hippocampal neurogenesis remains unclear. In the present study, we found that the number of doublecortin-positive cells in the hippocampus was decreased, and the dendritic length and number of intersections in newborn neurons in the hippocampus were reduced in transgenic adult mice with CX3CR1 deficiency （CX3CRl^GFP/GFe）. Furthermore, after experimental seizures were induced with kainic acid in these CX3CRl-deficient mice, the expression of c-fos, a marker of neuronal activity, was reduced compared with wild-type mice. Collectively, the experimental findings indicate that the functional maturation of newborn neu- rons during hippocampal neurogenesis in adult mice is delayed by CX3CR1 deficiency.展开更多
The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a mo...The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.展开更多
The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneit...The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in per- forming both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses （WGCNA）, we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neu- ronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.展开更多
Demyelination of the central nervous system（CNS）is a hallmark of multiple sclerosis（MS）,chronic inflammatory and neurodegenerative disease.Chronic demyelination favors neurodegeneration of denuded axons,which is a...Demyelination of the central nervous system（CNS）is a hallmark of multiple sclerosis（MS）,chronic inflammatory and neurodegenerative disease.Chronic demyelination favors neurodegeneration of denuded axons,which is a major cause of irreversible neuronal deficits and disability in MS patients（Lucchinetti et al.,2000）.展开更多
BACKGROUND： Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical ...BACKGROUND： Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions. OBJECTIVE： In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on intemeuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns. METHODS： We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations： ＂intemeuron＂, ＂somatosensory＂, ＂development＂, ＂activity＂, ＂network patterns＂, ＂thalamocortical＂, ＂NMDA receptor＂, ＂plasticity＂. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab. RESULTS： We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and pattems of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016. CONCLUSIONS： Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.展开更多
文摘Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i （CX3CRI） signaling pathway. However, whether microglia can influence the maturation and dendritic growth of newborn neurons during hippocampal neurogenesis remains unclear. In the present study, we found that the number of doublecortin-positive cells in the hippocampus was decreased, and the dendritic length and number of intersections in newborn neurons in the hippocampus were reduced in transgenic adult mice with CX3CR1 deficiency （CX3CRl^GFP/GFe）. Furthermore, after experimental seizures were induced with kainic acid in these CX3CRl-deficient mice, the expression of c-fos, a marker of neuronal activity, was reduced compared with wild-type mice. Collectively, the experimental findings indicate that the functional maturation of newborn neu- rons during hippocampal neurogenesis in adult mice is delayed by CX3CR1 deficiency.
基金supported by the National Natural Science Foundation of China,No.30800322Shanghai Pujiang Program,No.08PJ1401300+4 种基金Shanghai Leading Academic Discipline Project,No.B111Ministry of Education Research Fund for New Teachers in Doctoral Program of Higher Educational Institutes,No.200802461050National Basic Research Program of China(973 Program),No.2011CB503703Ministry of Education Start Fund to Returned Overseas ScholarsZhuo Xue Program of Fudan University
文摘The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.
基金The online version of this article （doi：10.1007/s13238-016-0247-8） contains supplementary material, which is available to authorized users.This work was supported by the National Basic Research Program （973 Program） （No. 2012CB966303）, the National Natural Science Foundation of China （Grant Nos. 81330030, 91319309, and 31271371）, the Science and Technology Department of Yunnan Province （Grant 2012HA013）, the Yunnan Basic Research Projects （Grant 2014FC004）, and the Doctoral Tutor of Education Department of Shanghai, China （Grant 20130072110021 ）, grants from NASAD： BRN ＆ BEHV RES FND 23072, NIH R21：IR21NS095184-01 and finally, a fellowship from China Scholarship Council to X. -Y.C.
文摘The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in per- forming both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses （WGCNA）, we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neu- ronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.
基金supported by Spanish Ministry of Economy and Competitiveness(BFU2014-55459P)Part of this research was presented at X FENS Forum of Neuroscience,Copenhagen,Denmark,July 2016(poster presentation)“Astrocyte-targeted production of IL-6 reduces demyelination,axonal pathology and microglial activation in the cuprizone-mediated demyelination model”
文摘Demyelination of the central nervous system（CNS）is a hallmark of multiple sclerosis（MS）,chronic inflammatory and neurodegenerative disease.Chronic demyelination favors neurodegeneration of denuded axons,which is a major cause of irreversible neuronal deficits and disability in MS patients（Lucchinetti et al.,2000）.
文摘BACKGROUND： Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions. OBJECTIVE： In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on intemeuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns. METHODS： We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations： ＂intemeuron＂, ＂somatosensory＂, ＂development＂, ＂activity＂, ＂network patterns＂, ＂thalamocortical＂, ＂NMDA receptor＂, ＂plasticity＂. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab. RESULTS： We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and pattems of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016. CONCLUSIONS： Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.
