The Ning Tian Laboratory
Neuronal signals are processed in vertebrate central nervous system 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 central nervous system, including 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 retina. The goals of our research are 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. Our principal strategies are to examine retinal neuron synaptic connectivity and activity at different stages of development under normal and pathological conditions and to test specific hypotheses using appropriate transgenic animal models.
To determine how RGC synaptic connectivity and activity are regulated during normal development, we have examined the maturation of RGC dendritic stratification patterns using confocal imaging and transgenic mouse models, in which fluorescent proteins are constitutively expressed in RGCs. We have also developed patch-clamp recording techniques and established a multiple electrode array system to measure retinal neuron synaptic activity from a retinal slice preparation and concurrent spike activity from multiple RGCs in whole-mount mouse retina. Using these techniques, we have shown significant maturational changes in the RGC dendritic structure and synaptic activity before and after retina receives visual stimulation (before and after eye opening). To determine the roles of visual experience on the development of synaptic connectivity and activity in retina and to understand the mechanisms of experience-dependent synaptic plasticity, we examined the effect of light deprivation on the maturation of RGCs by raising the animals in constant darkness after birth. We found that light deprivation completely blocked the maturational processes of RGC dendritic stratification. Consistent with the changes in RGC dendritic morphology, the maturation of RGC light responsiveness is also halted in dark reared mice.
The results of these studies have important implications in how we view pathologies that affect vision during infancy and childhood. They also provide insights to how retinal outputs to higher centers of visual system could be changed during activity-dependent synaptic plasticity in those centers and, therefore, affect our interpretation of activity-dependent synaptic plasticity in visual cortex.