Dendritic integration at the retinogeniculate synapse

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Project Summary One of the most remarkable properties of the brain is its ability to compute and integrate information. In the visual system, processing of visual scenes begins in the eye, where the underlying retinal circuitry segregates information into 30 – 40 distinct functional channels, each encoding one particular visual feature. Retinal ganglion cells (RGCs), the output neurons of the retina, relay these signals to downstream visual centers where they are integrated to mediate perception and drive behavior. The retinogeniculate synapse in the dorsal lateral geniculate nucleus (dLGN) represents the first connection between the eye and the brain and has been widely studied across multiple species. A prominent feature of the retinogeniculate synapse is that retinal inputs have a high propensity to organize into synaptic triads with inhibitory terminals and the postsynaptic dendrite creating a local circuit for fast feedforward inhibition. Recent studies have demonstrated that signals from multiple RGC types converge onto thalamocortical (TC) neurons, even at the level of individual dendrites. The extent of which different RGC types participate in these synaptic triads and how inhibition shapes integration of information from the retina in the dLGN is poorly understood. Retinogeniculate triads ensure that excitation and inhibition arrive with high spatiotemporal precision onto dendritic appendages of TC neurons. The overall goal of this proposal is to understand the function of retinogeniculate triads in coordinating dendritic integration at the retinogeniculate synapse. Specifically, this study will address two aims: (1)To assess the functional organization of RGC types into retinogeniculate triads and (2) To determine how local feedforward inhibition transforms responses in TC dendrites. The proposed experiments involve high-resolution visualization of synaptic input organization along TC dendrites and manipulation of activity in presynaptic terminals to understand how incoming visual signals are integrated across dendritic compartments. In conducting these experiments, I will learn how to pair optogenetics/chemogenetics with physiological methods, including patch-clamp electrophysiology and calcium imaging. Additionally, I will receive extensive training in large-scale data analysis for experiments related to super-resolution microscopy, electron microscopy, and in vivo calcium imaging. This proposed research will provide unique training that will prepare me for an independent career in dendritic and sensoryintegration.