The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous huma...The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved.One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.展开更多
Acid-sensing ion channels(ASICs),the main H^(+)receptors in the central nervous system,sense extracellular pH fluctuations and mediate cation influx.ASIC1a,the major subunit responsible for acid-activated current,is w...Acid-sensing ion channels(ASICs),the main H^(+)receptors in the central nervous system,sense extracellular pH fluctuations and mediate cation influx.ASIC1a,the major subunit responsible for acid-activated current,is widely expressed in brain neurons,where it plays pivotal roles in diverse functions including synaptic transmission and plasticity.However,the underlying molecular mechanisms for these functions remain mysterious.Using extracellular epitope tagging and a novel antibody recognizing the hASIC1a ectodomain,we examined the membrane targeting and dynamic trafficking of hASIC1a in cultured cortical neurons.Surface hASIC1a was distributed throughout somata and dendrites,clustered in spine heads,and co-localized with postsynaptic markers.By extracellular pHluorin tagging and fluorescence recovery after photobleaching,we detected movement of hASIC1a in synaptic spine heads.Single-particle tracking along with use of the anti-hASIC1a ectodomain antibody revealed long-distance migration and local movement of surface hASIC1a puncta on dendrites.Importantly,enhancing synaptic activity with brain-derived neurotrophic factor accelerated the trafficking and lateral mobility of hASIC1a.With this newly-developed toolbox,our data demonstrate the synaptic location and high dynamics of functionallyrelevant hASIC1a on the surface of excitatory synapses,supporting its involvement in synaptic functions.展开更多
基金supported by the National Natural Science Foundation of China(91632304 and 31500671)
文摘The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved.One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.
基金This work was supported by grants from the National Natural Science Foundation of China(81961128024 and 81730095)the Innovative Research Team of High-level Local Universities in Shanghai+2 种基金the Science and Technology Commission of Shanghai Municipality(18JC1420302)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the US National Institutes of Health(NS114716).
文摘Acid-sensing ion channels(ASICs),the main H^(+)receptors in the central nervous system,sense extracellular pH fluctuations and mediate cation influx.ASIC1a,the major subunit responsible for acid-activated current,is widely expressed in brain neurons,where it plays pivotal roles in diverse functions including synaptic transmission and plasticity.However,the underlying molecular mechanisms for these functions remain mysterious.Using extracellular epitope tagging and a novel antibody recognizing the hASIC1a ectodomain,we examined the membrane targeting and dynamic trafficking of hASIC1a in cultured cortical neurons.Surface hASIC1a was distributed throughout somata and dendrites,clustered in spine heads,and co-localized with postsynaptic markers.By extracellular pHluorin tagging and fluorescence recovery after photobleaching,we detected movement of hASIC1a in synaptic spine heads.Single-particle tracking along with use of the anti-hASIC1a ectodomain antibody revealed long-distance migration and local movement of surface hASIC1a puncta on dendrites.Importantly,enhancing synaptic activity with brain-derived neurotrophic factor accelerated the trafficking and lateral mobility of hASIC1a.With this newly-developed toolbox,our data demonstrate the synaptic location and high dynamics of functionallyrelevant hASIC1a on the surface of excitatory synapses,supporting its involvement in synaptic functions.
