About Our Lab
The principal strategies of Ning Tian, PhD, and his lab are to examine retinal ganglion cell (RGC) synaptic connectivity and activity at different stages of development under normal and pathological conditions and to test specific hypotheses using appropriate transgenic animal models.
Research Overview
Neuronal signals are processed in vertebrate CNS through parallel synaptic pathways. These synaptic pathways are formed with distinct cellular and molecular components and, in some cases, regulated by different mechanisms during development. In many parts of CNS, including the visual system, a fundamental anatomical feature of the parallel synaptic pathways is the histologically discrete laminar structure. The cellular and molecular specificity of the laminar structure appears to be a major determinant of the specific synaptic pathways.
In vertebrate retina, synaptic pathways processing different aspects of visual signals are also formed with different neuronal subtypes and synaptic structures in distinct laminae. This laminar structure is not mature at birth and continues to develop during postnatal ages in most mammalian retinas. Dr. Tian and his lab seek to understand the cellular and molecular mechanisms, which regulate the development of the retinal synaptic pathways and the formation of the laminar structure, and how these mechanisms are modulated under normal and pathological conditions.
NIH Funding FY23: Mechanisms Underlying CD3zeta Guided Assembly of Retinal Circuits
Exploring Retinal Synaptic Circuitry
To determine how RGC synaptic connectivity is regulated during normal development, the Tian Lab examined the dendritic and axonal structure of RGCs using in vivo and in vitro confocal imaging and transgenic mouse models, in which green or yellow fluorescent proteins (GFP or YFP) are constitutively expressed in RGCs.
The lab found that both RGC dendritic ramification in the retina and axonal projection in the higher centers of the visual system, such as dLGN, undergo active refinement after birth in mice. This developmental refinement is regulated by retinal synaptic activity. Blockade of either spontaneous or light-evoked retinal synaptic activity impaired the normal development of RGC synaptic connectivity in both retina and dLGN.
Using laser confocal time-lapse imaging, Dr. Tian can visualize mouse RGC dendritic remodeling and quantify the kinetics of the morphological refinement. Using electrophysiological recordings, such as patch-clamp recording of synaptic activity of individual retinal neurons or multiple electrode array recording of concurrent spike activity from multiple RGCs, the lab detected significant maturational changes of RGC spontaneous synaptic activity and light responsiveness during postnatal development. These age-dependent changes in retinal synaptic activity play an important role in the maturation of synaptic circuitry of the visual system.
Dr. Tian is also investigating the molecular mechanism that links the developmental changes of synaptic activity to the changes in synaptic structure. Surprisingly, the lab found that an immune molecule (CD3, which is a key element of T-cell receptor), is expressed by retinal neurons and is involved in the activity-dependent developmental regulation of RGC dendritic maturation in the retina and axonal projection in the dLGN. Impaired eye-specific segregation of mouse RGC axonal projections in the dLGN due to pharmacological blockade of spontaneous synaptic activity mediated by the glutamate receptor in the retina.
The results of these studies provide insights into how retinal synaptic circuitry could be changed during activity-dependent synaptic plasticity. They also have important implications for how to view pathologies that affect vision during infancy and childhood.
Select Publications from the Tian Laboratory
- CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina. Du R, Wang P, Tian N. Cells. 2024 Jun 8;13(12):1006.
- An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells. Young BK, Ramakrishnan C, Ganjawala T, Wang P, Deisseroth K, Tian N.Proc Natl Acad Sci USA. 2021 Nov 2;118(44):e2104884118.
- Visual Deprivation Retards the Maturation of Dendritic Fields and Receptive Fields of Mouse Retinal Ganglion Cells. Chen H, Xu HP, Wang P, Tian N. Front Cell Neurosci. 2021 Apr 27;15:640421.
- The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific. Yang N, Young BK, Wang P, Tian N. Cells. 2020 Mar 10;9(3):677.
- A Unique and Evolutionarily Conserved Retinal Interneuron Relays Rod and Cone Input to the Inner Plexiform Layer. Young B, Ramakrishnan C, Ganjawala T, Li Y, Kim S, Wang P, Chen R, Deisseroth K, Tian N. bioRxiv. 2020 May.
- The Immune Protein CD3z Is Required for Normal Development of Neural Circuits in the Retina. Xu HP, Chen H, Ding Q, Xie ZH, Chen L, Diao L, Wang P, Gan L, Crair MC, Tian N. Neuron, 2010; 65:503-515.
- Glycine receptor-mediated synaptic transmission regulates the visual activity-dependent maturation of retinal ganglion cell synaptic connectivity. Xu HP, Tian N. J Comp Neurol, 2008; 509:53-71.
- Retinal ganglion cell dendrites undergo a visual activity-dependent Redistribution after eye-opening. Xu HP, Tian N. J Comp Neurol, 2007; 503:244-259.
- Light deprivation induced suppression of light response in mouse retina. Vistamehr S, Tian N. Vis Neurosci, 2004; 21:23-37.
- Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina. Tian N, Copenhagen DR. Neuron, 2003; 39:85-96.
- Visual deprivation alters development of synaptic function in inner retina after eye opening. Tian N Copenhagen DR. Neuron, 2001; 32: 439-449.
- The roles of the synthetic enzyme GAD65 in the control of neuronal y-aminobutyric acid release. Tian N, Peterson C, Kash S, Baekkeskov, S, Copenhagen DR, Nicoll RA. Proc Natl Acad Sci U S A, 1999; 96:12911-12916.
News From the Tian Laboratory
Tian Lab Retinal Cell Discovery
The newly identified Campana cell could play a role in visual signal processing.