Plasticity of the Retinogeniculate Synapse

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ABSTRACT 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.