The proper formation of sensory systems, such as the visual system, requires experience-dependent refinement. Traditionally, it was believed that sensory-dependent plasticity was limited to cortex and began only after subcortical pathways had stabilized. However recent studies from many laboratories, including ours, have demonstrated that experience-dependent plasticity also occurs outside of cortical circuits. Studies from the Chen laboratory have revealed that refinement of the retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and thalamic relay neurons, continues far beyond early development and includes a critical period during which pre- and post-synaptic partners can change in a vision-dependent manner. The discovery of late-stage functional plasticity in the thalamus represents a significant shift in our understanding of sensor system development, as it implies that subcortical circuits rewire with experience concurrently with cortex. Furthermore, the presence of extensive feedback projections from cortex that innervate thalamus just prior to the onset of this critical period suggests that, in contrast to th model of sequential, feedforward development of sensory pathways, subcortical structures may actually incorporate feedback from cortex to mature properly. Indeed, here we present strong preliminary data supporting this hypothesis. In this proposal, we outline experiments to further explore the purpose and mechanisms of experience-dependent thalamic plasticity, as well as the cortical contributions to this process. We will take advantage of optogenetic and pharmacogenetic tools to manipulate and characterize specific circuit components throughout development.
The results from the proposed studies in a simple experimental model system will provide important information on mechanisms that can regulate the proper formation of a sensory circuit. Understanding these basic processes will help guide the design of future therapies for neurological disorders due to disrupted neuronal circuits, such as in amblyopia, as well as some forms of epilepsy, cognitive disorders and 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 |
Showing the most recent 10 out of 22 publications
