Plasticity of the Retinogeniculate Synapse

Boston Children'S Hospital, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): 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.