Shigang He

Northeast Institute of Geography and Agroecology, Peping, Beijing, China

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Publications (18)120.73 Total impact

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    ABSTRACT: In the adult rabbit and mouse retina, about 30% of the ON-OFF direction selective ganglion cells (DSGCs) are coupled via gap junctions. In early postnatal rabbit retinas, a greater proportion of morphological ON-OFF DSGCs shows coupling with a larger number of nearby somas. It is not clear whether the coupled ON-OFF DSGCs belong to the same subtype, or how coupling patterns change during development. In this study, we showed that in adult mouse retinas, all coupled ON-OFF DSGCs exhibited preferred directions (PDs) to superior, and this pattern emerged at postnatal day 15 (P15). At P13, the ON-OFF DSGCs with PDs to posterior were also coupled. Every ON-OFF DSGC in every subtype injected at P12 exhibited coupling. Therefore, a rapid decoupling process takes place in DSGCs around eye opening. Light deprivation delayed but did not halt the decoupling process. By using a transgenic mouse line in which GFP is selectively expressed in DSGCs with PDs to posterior and by performing in situ hybridization of cadherin-6, a marker for the DSGCs with PDs to superior and inferior, we showed that heterologous coupling existed between DSGCs with PDs to anterior and posterior till P12, but this heterologous coupling never spread to DSGCs positive for cadherin-6.
    Neuroscience 06/2013; · 3.12 Impact Factor
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    ABSTRACT: Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), γ-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine.
    Cell Research 11/2011; 22(1):208-18. · 10.53 Impact Factor
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    Le Sun, Xu Han, Shigang He
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    ABSTRACT: The ON-OFF direction selective ganglion cells (DSGCs) in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.
    PLoS ONE 01/2011; 6(5):e19477. · 3.73 Impact Factor
  • XiuLan Yang, XiangMing Shi, ShiGang He
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    ABSTRACT: The property of dendritic growth dynamics during development is a subject of intense interest. Here, we investigated the dendritic motility of retinal ganglion cells (RGCs) during different developmental stages, using ex vivo mouse retina explant culture, Semliki Forest Virus transfection and time-lapse observations. The results illustrated that during development, the dendritic motility underwent a change from rapid growth to a relatively stable state, i.e., at P0 (day of birth), RGC dendrites were in a highly active state, whereas at postnatal 13 (P13) they were more stable, and at P3 and P8, the RGCs were in an intermediate state. At any given developmental stage, RGCs of different types displayed the same dendritic growth rate and extent. Since the mouse is the most popular mammalian model for genetic manipulation, this study provided a methodological foundation for further exploring the regulatory mechanisms of dendritic development.
    Science China. Life sciences 06/2010; 53(6):669-76. · 2.02 Impact Factor
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    ShiGang He
    Science China. Life sciences 01/2010; 53(1):150. · 2.02 Impact Factor
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    ABSTRACT: During early postnatal development, dendrites of retinal ganglion cells (RGCs) extend and branch in the inner plexiform layer to establish the adult level of stratification, pattern of branching, and coverage. Many studies have described the branching patterns, transient features, and regulatory factors of stratification of the RGCs. The rate of RGC dendritic field (DF) expansion relative to the growing retina has not been systematically investigated. In this study, we used two methods to examine the relative expansion of RGC DFs. First, we measured the size of RGC DFs and the diameters of the eyeballs at several postnatal stages. We compared the measurements with the RGC DF sizes calculated from difference of the eyeball sizes based on a linear expansion assumption. Second, we used the number of cholinergic amacrine cells (SACs) circumscribed by the DFs of RGCs at corresponding time points as an internal ruler to assess the size of DFs. We found most RGCs exhibit a phase of faster expansion relative to the retina between postnatal day 8 (P8) and P13, followed by a phase of retraction between P13 and adulthood. The morphological alpha cells showed the faster growing phase but not the retraction phase, whereas the morphological ON-OFF direction selective ganglion cells expanded in the same pace as the growing retina. These findings indicate different RGCs show different modes of growth, whereas most subtypes exhibit a fast expansion followed by a retraction phase to reach the adult size.
    Developmental Neurobiology 12/2009; 70(6):397-407. · 4.42 Impact Factor
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    ABSTRACT: The thalamic reticular nucleus (TRN) is thought to function in the attentional searchlight. We analyzed the detection of deviant acoustic stimuli by TRN neurons and the consequences of deviance detection on the TRN target, the medial geniculate body (MGB) of the rat. TRN neurons responded more strongly to pure-tone stimuli presented as deviant stimuli (low appearance probability) than those presented as standard stimuli (high probability) (deviance-detection index = 0.321). MGB neurons also showed deviance detection in this procedure, albeit to a smaller extent (deviance-detection index = 0.154). TRN neuron deviance detection either enhanced (14 neurons) or suppressed (27 neurons) MGB neuronal responses to a probe stimulus. Both effects were neutralized by inactivation of the auditory TRN. Deviance modulation effects were cross-modal. Deviance detection probably causes TRN neurons to transiently deactivate surrounding TRN neurons in response to a fresh stimulus, altering auditory thalamus responses and inducing attention shift.
    Nature Neuroscience 09/2009; 12(9):1165-70. · 15.25 Impact Factor
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    ABSTRACT: Selective responses of retinal ganglion cells (RGCs) to the direction of motion have been recorded extracellularly from the rabbit and the mouse retina at eye opening. Recently, it has been shown that the development of this circuitry is light independent. Using whole-cell patch clamp recording, we report here that mouse early postnatal direction-selective ganglion cells (DSGCs) showed lower membrane excitability, lower reliability of synaptic transmission and much slower kinetics of light responses compared with adult DSGCs. However, the degree of direction selectivity of early postnatal DSGCs measured by the direction-selective index and the width of the directional tuning curve was almost identical to that of adult DSGCs. The DSGCs exhibited a clear selectivity for the direction of motion at the onset of light sensitivity. Furthermore, the degree of direction selectivity was not affected by rearing in complete darkness from birth to postnatal day 11 or 30. The formation of the retinal neurocircuitry for coding motion direction is completely independent of light.
    The Journal of Physiology 01/2009; 587(Pt 4):819-28. · 4.38 Impact Factor
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    ABSTRACT: Responses to repeated auditory stimuli were examined in 103 neurons in the auditory region of the thalamic reticular nucleus (TRN) and in 20 medial geniculate (MGB) neurons of anesthetized rats. A further six TRN neurons were recorded from awake rats. The TRN neurons showed strong responses to the first trial and weak responses to the subsequent trials of repeated auditory stimuli and electrical stimulation of the MGB and auditory cortex when the interstimulus interval (ISI) was short (<3 s). They responded to the second trial when the interstimulus interval was lengthened to >or=3 s. These responses contrasted to those of MGB neurons, which responded to repeated auditory stimuli of different ISIs. The TRN neurons showed a significant increase in the onset auditory response from 9.5 to 76.5 Hz when the ISI was increased from 200 ms to 10 s (P<0.001, ANOVA). The duration of the auditory-evoked oscillation was longer when the ISI was lengthened. The slow recovery of the TRN neurons after oscillation of burst firings to fast repetitive stimulus was a reflection of a different role than that of the thalamocortical relay neurons. Supposedly the TRN is involved in the process of attention such as attention shift; the slow recovery of TRN neurons probably limits the frequent change of the attention in a fast rhythm.
    Journal of Neurophysiology 12/2008; 101(2):980-7. · 3.30 Impact Factor
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    Shigang He
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    ABSTRACT: Using a transgenic mouse line in which GFP is expressed in a single population of retinal ganglion cells (RGCs), Huberman and colleagues report in this issue of Neuron that the axon terminals of RGCs exhibit an orderly pattern of distribution in the higher visual centers. This pattern undergoes a developmental refinement, and synchronous activity in the retina regulates columnar but not laminar formation.
    Neuron 09/2008; 59(3):352-3. · 15.77 Impact Factor
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    ABSTRACT: Two types of ganglion cells (RGCs) compute motion direction in the retina: the ON-OFF direction-selective ganglion cells (DSGCs) and the ON DSGCs. The ON DSGCs are much less studied mostly due to the low encounter rate. In this study, we investigated the physiology, dendritic morphology and synaptic inputs of the ON DSGCs in the mouse retina. When a visual stimulus moved back and forth in the preferred-null axis, we found that the ON DSGCs exhibited a larger EPSC when the visual stimulus moved in the preferred direction and a larger IPSC in the opposite, or null direction, similar to what has been found in ON-OFF DSGCs. This similar synaptic input pattern is in contrast to other well-known differences, namely: profile of velocity sensitivity, distribution of preferred directions, and different central projection of the axons. Immunohistochemical staining showed that the dendrites of ON DSGCs exhibited tight cofasciculation with the cholinergic plexus. These findings suggest that cholinergic amacrine cells may play an important role in generating direction selectivity in the ON DSGCs, and that the mechanism for coding motion direction is probably similar for the two types of DSGCs in the retina.
    The Journal of Physiology 11/2006; 576(Pt 1):197-202. · 4.38 Impact Factor
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    ABSTRACT: We examined the identities of horizontal cell (HC) lateral components in cone terminals and the expression of glutamate receptors on the tips of HC dendrites. We injected A-type horizontal cells (AHCs) with neurobiotin and demonstrated that neurobiotin labeled completely all AHCs within a patch of retina. We converted neurobiotin by using diaminobenzidine and considered labeled processes to be from AHCs and unlabeled processes to be from B-type horizontal cells (BHCs). Three possible combinations of HC dendrites could exist in cone pedicles: both lateral components originating from AHCs, both from BHCs, or one from an AHC and the other from a BHC. EM observations revealed that a majority of cone terminals contained about equal numbers of lateral components originating from each of the two types of HCs and that each of the three possible combinations was present in equal numbers. Localization of different types of glutamate receptors on HC dendritic tips showed that 55% of AHC dendritic tips expressed AMPA receptors and 30% expressed kainate receptors, whereas, in the case of BHCs, 22% of dendritic tips expressed AMPA receptors and 33% expressed kainate receptors. This study suggests that cone photoreceptors feed the light signal equally into networks of AHCs and BHCs and that differential expression of AMPA/kainate receptors by different HCs could account for different functions.
    The Journal of Comparative Neurology 07/2006; 496(5):698-705. · 3.66 Impact Factor
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    Shijun Weng, Wenzhi Sun, Shigang He
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    ABSTRACT: We identified the ON-OFF direction-selective ganglion cells (DSGCs) in the mouse retina and characterized their physiological, morphological and pharmacological properties. These cells showed transient responses to the onset and termination of a stationary flashing spot, and strong directional selectivity to a moving rectangle. Application of various pharmacological reagents demonstrated that the ON-OFF DSGCs in the mouse retina utilize a similar array of transmitters and receptors to compute motion direction to their counterparts in the rabbit retina. Voltage clamp recording showed that ON-OFF DSGCs in the mouse retina receive a larger inhibitory input when the stimulus is moving in the null direction and a larger excitatory input when the stimulus is moving in the preferred direction. Finally, intracellular infusion of neurobiotin revealed a bistratified dendritic field with recursive dendrites forming loop-like structures, previously classified as RG(D2) by morphology. Overall, the ON-OFF DSGCs in the mouse retina exhibit almost identical properties to their counterparts in the rabbit retina, indicating that the mechanisms for computing motion direction are conserved from mouse to rabbit, and probably also to higher mammals. This first detailed characterization of ON-OFF DSGCs in the mouse retina provides fundamental information for further study of maturation and regulation of the neuronal circuitry underlying computation of direction.
    The Journal of Physiology 03/2005; 562(Pt 3):915-23. · 4.38 Impact Factor
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    ABSTRACT: The time course and regulatory mechanisms of dendritic development are subjects of intense interest. We approached these problems by investigating dendritic morphology of retinal ganglion cells (RGCs) at four early postnatal stages. The RGCs develop from a diffusely stratified and poorly differentiated group at birth (P0), to 16 distinct, morphologically well-defined subtypes before eye opening (P13). Even before bipolar cells make synaptic contacts with the RGCs (P8), most adultlike RGC subtypes are already present. Similar to previous studies in other mammalian species, our results indicate that the initiation of the RGC morphological maturation is independent of light stimulation and of formation of glutamatergic synapses. This study narrowed down the window of RGCs morphological maturation and highlighted a few early postnatal events as potential factors controlling the developmental process. Because mouse is the most popular mammalian model for genetic manipulation, this study provided a foundation for further exploring regulatory mechanisms of RGC dendritic development.
    Journal of Neurobiology 12/2004; 61(2):236-49. · 3.05 Impact Factor
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    ABSTRACT: We investigated the dendritic relationship between starburst amacrine cells (SAs) and morphologically and physiologically characterized ON and ON-OFF direction-selective ganglion cells (DSGCs) in the rabbit retina. ON and ON-OFF DSGCs were found to exhibit tight dendritic cofasciculation with the SA plexus, visualized by immunolabelling of the vesicular acetylcholine transporter (VAChT). The degree of cofasciculation of both types of DSGC dendrites and SA plexus was found to be significant, unlike the relationship between non-DS cells and the SA plexus, which was close to chance distribution. No difference in the degree of cofasciculation in different regions of the DS dendritic field was observed. Individual SAs intracellularly injected both on the 'preferred' and 'null' side of the DSGCs showed the same degree of cofasciculation with the DSGCs. Therefore, the computation of motion direction is unlikely to result from apparent asymmetry in geometric proximity between SAs and DSGCs. Highly selective synaptic connections between SAs and DSGCs are necessary.
    The Journal of Physiology 05/2004; 556(Pt 1):11-7. · 4.38 Impact Factor
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    ABSTRACT: Among 10 breakthroughs that Science announced at the end of 2002 was the discovery of a photosensing (melanopsin-containing) retinal ganglion cell (RGC) and its role in entraining the circadian clock. This breakthrough exemplifies the ultimate goal of neuroscience: to understand the nervous system from molecules to behavior. Light-sensing RGCs constitute one of a dozen discrete RGC populations coding various aspects of visual scenes by virtue of their unique morphology, physiology, and coverage of the retina. Interestingly, the function of the melanopsin-containing RGCs in entraining the circadian clock need not involve much retinal processing, making it the simplest form of processing in the retina. This review focuses on recent advances in our understanding of retinal circuitry, visual processing, and retinal development demonstrated by innovative experimental techniques. It also discusses the advantages of using the retina as a model system to address some of the key questions in neuroscience.
    Science 11/2003; 302(5644):408-11. · 31.20 Impact Factor
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    Wenzhi Sun, Ning Li, Shigang He
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    ABSTRACT: Five hundred twenty ganglion cells in an isolated whole-mount preparation of the mouse retina were labeled using the "DiOlistic" method (Gan et al. [2000] Neuron 27:219-225) and were classified according to their morphological properties. Tungsten particles coated with a lipophilic dye (DiI) were propelled into the whole-mount retina using a gene gun. When a dye-coated particle contacted the cell membrane, the entire cell was labeled. The ganglion cells were classified into four groups based on their soma size, dendritic field size, and pattern and level of stratification. Broadly monostratified cells were classified into three groups: RG(A) cells (large soma, large dendritic field), RG(B) cells (small to medium-sized soma, small to medium-sized dendritic field), and RG(C) cells (small to medium-sized size soma, medium-sized to large dendritic field). Bistratified cells were classified as RG(D). This study represents the most complete morphological classification of mouse retinal ganglion cells available to date and provides a foundation for further understanding of the correlation of physiology and morphology and ganglion cell function with genetically manipulated animals.
    The Journal of Comparative Neurology 10/2002; 451(2):115-26. · 3.66 Impact Factor
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    Wenzhi Sun, Ning Li, Shigang He
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    ABSTRACT: Ganglion cells in an isolated wholemount preparation of the rat retina were labeled using the "DiOlistic" labeling method (Gan et al., 2000) and were classified according to their morphological properties. Tungsten particles coated with a lipophilic dye (DiI) were propelled into the wholemount retina using a gene gun. When a dye-coated particle contacted the cell membrane, the entire cell was labeled. The ganglion cells were classified into four types based on their soma size, dendritic-field size, branching pattern, and level of stratification. Broadly monostratified cells were classified into three types: RG(A) cells (large soma, large dendritic field); RG(B) cells (small- to medium-sized soma, small- to medium-sized dendritic field); and RG(C) cells (small- to medium-sized soma, medium-to-large dendritic field). Bistratified cells were classified as RG(D). Several subtypes were identified within each ganglion cell group. A number of new subtypes were discovered and added into the existing catalog, among them were two types of bistratified cells. This study therefore represents the most complete morphological classification of rat retinal ganglion cells available to date.
    Visual Neuroscience 01/2002; 19(4):483-93. · 1.48 Impact Factor

Publication Stats

506 Citations
120.73 Total Impact Points

Institutions

  • 2003–2013
    • Northeast Institute of Geography and Agroecology
      • • Institute of Biophysics
      • • Institute of Neuroscience
      Peping, Beijing, China
  • 2006–2010
    • Chinese Academy of Sciences
      • Institute of Biophysics
      Peping, Beijing, China
  • 2002–2006
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China