# Functional Dissection of New Retinal Circuits

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $623,328

## Abstract

The goal of this application is to understand the connectivity and function of a unique dual-transmitter
amacrine cell circuit, in an effort to gain a comprehensive understanding of the functional organization of local
neuronal circuits in the inner mammalian retina. Our recent studies discovered a number of intriguing synaptic
and dendritic properties of the vGluT3 amacrine cell (GAC) network (Lee et al., Neuron 84:1049-64, 2014; Lee
et al. Neuron 90: 27-34, 2016; Chen et al., PNAS 114:11518-11523, 2017), which offer an exciting opportunity
to use this new model circuit to address many fundamental, long-standing questions regarding amacrine cell
circuitry and function. Here, we propose to take a systematic approach to uncovering the connectivity and
function of the entire local circuit of GACs, from the inputs from upstream bipolar cell types to the outputs to
distinct downstream ganglion cell and amacrine cell types. The proposed study will focus on identifying new
synaptic circuits between GACs and their synaptic partners and uncovering novel functional roles of GACs in
shaping the receptive field properties of their downstream targets. Using the GAC circuit as a central link, we
also aim to understand how the GAC circuit connectivity may help delineate the organization of other local circuits
in the retina. There are three specific aims in this proposal: (1) to understand the synaptic connectivity and
synaptic interactions between cone bipolar cell (CBC) types and GACs, (2) to understand function of a new
glycinergic output circuit from GACs to ganglion cells, (3) to understand network interactions between GACs and
other amacrine cell types. We will take an innovative approach to this goal by combining state-of-art
electrophysiological (dual patch clamp in the inner nuclear layer of the wholemount mouse retina), optical
(simultaneous two-photon imaging of local dendritic responses and patch clamp), genetic (in vivo viral
transfection of genes in selected single neurons), and optogenetic techniques in a robust whole-mount
preparation of vGluT3-Cre mouse retina. These techniques have been well tested in our recent studies and
have helped us generate a substantial amount of preliminary data that are critical for the proposed study. The
combination of these powerful tools with a unique, well-defined preparation offers an opportunity rarely attainable
in other parts of the CNS. Results from this proposed research will shed important light on retinal circuit
organization and function in health and disease.

## Key facts

- **NIH application ID:** 9850569
- **Project number:** 5R01EY026065-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Z JIMMY ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $623,328
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850569

## Citation

> US National Institutes of Health, RePORTER application 9850569, Functional Dissection of New Retinal Circuits (5R01EY026065-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850569. Licensed CC0.

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