# Cell types and functional circuitry in the retina

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $383,150

## Abstract

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.

## Key facts

- **NIH application ID:** 10456763
- **Project number:** 5R01EY030169-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** YONGLING ZHU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $383,150
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456763

## Citation

> US National Institutes of Health, RePORTER application 10456763, Cell types and functional circuitry in the retina (5R01EY030169-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456763. Licensed CC0.

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