A wide variety of neurons and gIial cells differentiatefrom common precursor cells in the developing nervoussystem. During this process, Notch-mediated cell-cell in-teraction is essential for maintenance of dividing c...A wide variety of neurons and gIial cells differentiatefrom common precursor cells in the developing nervoussystem. During this process, Notch-mediated cell-cell in-teraction is essential for maintenance of dividing cells andsubsequellt generation of cell type diversity. Activation ofNotch inhibits cellular differentiation, and abnormality ofthe Notch pathway leads to premature neuronal differenti-ation, the lack of some cell types, and severe defects of tis-sue morphogenesis. Recent data demonstrate that Notchfails to inhibit cellular differentiation in the absence of thebHLH genes Hes1 and He5, which functionally afitago-nize the neuronal bHLH genes such as theh1- These re-sults indicate that the two Hes genes are essential effecorsfor the Notch pathway and that neuronal differentiation iscontrolled by the pathway "Notch-+He1/Hs5,Mish1".展开更多
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal contr...Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.展开更多
Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activit...Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.展开更多
The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this class...The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the wholecell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns： sustained-regular（n = 4） and sustained-adapting firing patterns（n = 3）. The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies.展开更多
Polybrominated diphenyl ether (PBDE) is a persistently environmental pollutant ubiquitously found in wildlife and humans. Although concern on PBDE’s toxic effects is steadily increasing, its action on the central ner...Polybrominated diphenyl ether (PBDE) is a persistently environmental pollutant ubiquitously found in wildlife and humans. Although concern on PBDE’s toxic effects is steadily increasing, its action on the central nervous system (CNS) remains largely unknown. To address this issue, the present study ex- amined the development inhibition of PBDE in neurons. The primary cultured hippocampal neurons of rat were exposed to the commercial decabromodiphenyl ether (deca-BDE), and the neurite length, bi- furcation, and synapse formation and maturation were evaluated, based on the confocal microscope imaging. The results showed that the development inhibition in neurons occurred at 15 μmol/L, indi- cating that PBDE is a potent neurotoxicant and it might obviously inhibit the development of cultured neurons.展开更多
文摘A wide variety of neurons and gIial cells differentiatefrom common precursor cells in the developing nervoussystem. During this process, Notch-mediated cell-cell in-teraction is essential for maintenance of dividing cells andsubsequellt generation of cell type diversity. Activation ofNotch inhibits cellular differentiation, and abnormality ofthe Notch pathway leads to premature neuronal differenti-ation, the lack of some cell types, and severe defects of tis-sue morphogenesis. Recent data demonstrate that Notchfails to inhibit cellular differentiation in the absence of thebHLH genes Hes1 and He5, which functionally afitago-nize the neuronal bHLH genes such as theh1- These re-sults indicate that the two Hes genes are essential effecorsfor the Notch pathway and that neuronal differentiation iscontrolled by the pathway "Notch-+He1/Hs5,Mish1".
基金supported in part by NIH NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,Merit Review Award I01 BX002356 from the U.SDepartment of Veterans Affairs,Craig H Neilsen Foundation 296749+1 种基金Indiana Spinal Cord and Brain Injury Research Foundation(ISCBIRF)019919Mari Hulman George Endowment Funds
文摘Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
基金supported by the National Natural Science Foundation of China,No.31500836,81671288the Natural Science Foundation of Anhui Province of China,No.1608085QH176
文摘Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.
基金supported by the National Natural Science Foundation of China,No.81271090
文摘The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the wholecell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns： sustained-regular（n = 4） and sustained-adapting firing patterns（n = 3）. The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies.
基金Supported by the National Basic Research Program of China (Grant No. 2003CB- 415001)the National Natural Science Foundation of China (Grant No. 30321002)the Chinese Academy of Sciences (Grant No. KJCX2-SW-H06)
文摘Polybrominated diphenyl ether (PBDE) is a persistently environmental pollutant ubiquitously found in wildlife and humans. Although concern on PBDE’s toxic effects is steadily increasing, its action on the central nervous system (CNS) remains largely unknown. To address this issue, the present study ex- amined the development inhibition of PBDE in neurons. The primary cultured hippocampal neurons of rat were exposed to the commercial decabromodiphenyl ether (deca-BDE), and the neurite length, bi- furcation, and synapse formation and maturation were evaluated, based on the confocal microscope imaging. The results showed that the development inhibition in neurons occurred at 15 μmol/L, indi- cating that PBDE is a potent neurotoxicant and it might obviously inhibit the development of cultured neurons.
