The formation and refinement of synaptic circuits are fundamental to neurological function. To understand the basic mechanisms and logic of neuronal circuit refinement, the Chen Lab uses the mouse visual system as our experimental model. This model offers a simplified circuitry and genetic accessibility and control of different neurons along the visual pathway. We study the connection between retinal ganglion cells (RGCs) in the eye and relay neurons in the dorsolateral geniculate nucleus (dLGN, the visual thalamus) of mice, a synapse that shows robust synaptic plasticity during development. Our studies have revealed that synaptic plasticity at the retinogeniculate synapse extends much longer than previously recognized?long after eye-opening in mice. We also found that that during this late developmental period, retinothalamic circuits undergo a critical period of experience-dependent refinement, previously thought to be an exclusive feature of cortical circuits. Notably, sensory experience during a late window of development can rewire retinogeniculate connectivity, changing both the strength and number of afferent retinal inputs onto a given thalamocortical neuron. In the prior funding period we demonstrated that, during the thalamic critical period, changes in cortical activity can feedback to the thalamus to alter connectivity of subcortical circuits. Our work demonstrates that rather than developing sequentially?with circuits of the eye maturing before those of the thalamus and still later the cortex?interactions between these stations of the visual pathway are critical for proper neurologic development. Yet, the question persists: What is the purpose of the thalamic experience-dependent critical period? Results from a recent study from our laboratory provide hints of an answer to this question?? in a collaborative effort with the Andermann Laboratory, we visualized retinal axons in the dLGN and found that different information lines from the retina converging onto a thalamocortical neuron are matched to specific features of the visual space to efficiently transmit tuned information. We now propose to test the idea that the exquisite organization of the retinogeniculate synapse gives rise to feature selectivity in the dLGN, and that these features are fine-tuned by cortical feedback during the thalamic critical period. Using a combination of tools including dual-color optogenetics, chemogenetics, in vitro slice electrophysiology, and in vivo single unit recordings along with in vivo imaging of retinal axon boutons, we propose a series of experiments to test the hypothesis that experience-dependent plasticity at the retinogeniculate synapse drives the fine-tuning of select receptive field features that are sensitive to environmental cues.
The results from the proposed studies will provide insight on how sensory experience over development can regulate the integration of information lines connecting the eye to the brain. Understanding these basic processes will help guide the design of future therapies for disorders of visual perception and amblyopia, as well as some forms of mental retardation.
| Lehrman, Emily K; Wilton, Daniel K; Litvina, Elizabeth Y et al. (2018) CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development. Neuron 100:120-134.e6 |
| Liang, Liang; Fratzl, Alex; Goldey, Glenn et al. (2018) A Fine-Scale Functional Logic to Convergence from Retina to Thalamus. Cell 173:1343-1355.e24 |
| Hong, Y Kate; Burr, Eliza F; Sanes, Joshua R et al. (2018) Heterogeneity of retinogeniculate axon arbors. Eur J Neurosci : |
| Thompson, Andrew; Gribizis, Alexandra; Chen, Chinfei et al. (2017) Activity-dependent development of visual receptive fields. Curr Opin Neurobiol 42:136-143 |
| Thompson, Andrew D; Chen, Chinfei (2017) The importance of constructive feedback: Implications of top-down regulation in the development of neural circuits. Neurogenesis (Austin) 4:e1287553 |
| Litvina, Elizabeth Y; Chen, Chinfei (2017) An evolving view of retinogeniculate transmission. Vis Neurosci 34:E013 |
| Litvina, Elizabeth Y; Chen, Chinfei (2017) Functional Convergence at the Retinogeniculate Synapse. Neuron 96:330-338.e5 |
| Chen, Chinfei; Bickford, Martha E; Hirsch, Judith A (2016) Untangling the Web between Eye and Brain. Cell 165:20-21 |
| Bei, Fengfeng; Lee, Henry Hing Cheong; Liu, Xuefeng et al. (2016) Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell 164:219-232 |
| Thompson, Andrew D; Picard, Nathalie; Min, Lia et al. (2016) Cortical Feedback Regulates Feedforward Retinogeniculate Refinement. Neuron 91:1021-1033 |
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