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High-probability grants
According to our matching algorithm, Yongling Zhu is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2019 — 2021 |
Zhu, Yongling |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cell Types and Functional Circuitry in the Retina @ Northwestern University At Chicago
The long-term goal of this research is to understand the visual processing in the inner plexiform layer of the retina. More immediately, the research serves to provide genetic access to distinct amacrine cell types for functional characterization and to understand how they shape the response properties of ganglion cells. Amacrine cells are the most diverse neurons in the retina, at least 40?50 morphological types have been described. Each type of amacrine cells exhibits a unique morphology and generates specific visual computations through their local circuits. Unfortunately, the great diversity of amacrine cells has been a major obstacle to access individual cell types for systematic studies. As a result, the connectivity and function of many amacrine cells remain unknown, and the development of genetic tools that allow for cell type-specific targeting and manipulation would be an important step towards their characterization. We propose to use new mouse intersectional genetic tools combined with functional imaging and electrophysiology recording to morphologically and functionally dissect amacrine cell circuits in three separate Aims. In Aim 1, we will create intersectional strategies by using a combination of Cre and tTA expression to discover new amacrine cell types and to target these cells with increased specificity. After that, we will focus on a newly discovered amacrine cell type called Ck2-AC1 for functional analysis. We will characterize the light responses of Ck2-AC1s by imaging Ca2+ responses at the sites of neurotransmitter release in Aim 1, and then identify their post-synaptic ganglion cells with intersectional ChR2 activation in Aim 2. In Aim 3, we will test specific hypotheses about Ck2-AC1s and examine their functional roles in different circuits with chemogenetic inactivation. We will use both hypothesis driven and discovery based approaches to gain insights into the circuit functions of Ck2-AC1s in the inner retina. The intersectional strategy is extensible, and we will undoubted discover additional novel amacrine cells and circuits utilizing the methods established for Ck2-AC1s. This work will advance our understanding of visual processing in the inner retina while the technologies developed will provide major advances over existing methods for studying amacrine cells and are also applicable to other brain circuits. Furthermore, this project will provide insight into pathophysiological neuronal mechanisms of retinal diseases, and help design better strategies for therapy.
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1 |
2021 |
Devries, Steven H [⬀] Zhu, Yongling |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Signal Processing in the Inner Retina @ Northwestern University At Chicago
The mammalian retina contains at least 40 types of retinal ganglion cells (RGCs) each tuned to respond best to different and sometimes complex features in a visual scene. Together, these diverse RGC responses provide us with all of the information that we use to navigate in the visual world. Each type of RGC monitors a patch on the retinal surface, its receptive field, by collecting inputs from presynaptic bipolar and amacrine cells of which there are more than 12 and 50 types, respectively. While the general patterns of amacrine and bipolar cell connectivity that contribute to RGC light responses are known, the daunting complexity of the inner synaptic layer of the retina has impeded our understanding of the connections that underlie the tuning properties that distinguish the RGC types. Specifically, there is currently no systematic way to identify all of the cells that make presynaptic inputs to an RGC and at the same time study their combined function as a processing unit. This proposal uses a toolbox of viral techniques to trace and functionally characterize the amacrine and bipolar cells that provide input to specific RGCs in both the rod dominant mouse and cone dominant ground squirrel retinas. In three specific aims, our goals are to: 1) use a trans-synaptic rabies virus that expresses GFP to map the direct bipolar and amacrine cell inputs to genetically targeted RGCs in the mouse retina? 2) use a trans-synaptic rabies virus that expresses the Ca2+ indicator protein GCaMP6 to study the functional connections between RGCs and their direct inputs from bipolar and amacrine cells in the mouse retina? and, 3) identify and functionally characterize the inner retinal circuits responsible for blue/green color opponent vision in the ground squirrel. Our work will define the wiring and functions of specific inner retinal circuits in health and provide the background for understanding circuit changes that are known to occur following photoreceptor degeneration, whether from genetic or age-onset disease.
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1 |