# Synaptic mechanisms and circuitry of retinal interneurons

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $517,134

## Abstract

Abstract
The goal of this proposal is to understand how visual signals are transmitted from the outer to the inner retina
through cone bipolar cells (CBC), with a focus on detailed synaptic mechanisms and functional circuits between
morphologically and physiologically identified cone bipolar cell types and specific ganglion and amacrine cell
types in the whole-mount mouse retina. This investigation is motivated by an important observation that,
although recent transcriptomic, connectomic, and imaging studies have significantly advanced our
understanding of bipolar cell classification and anatomical structure, our knowledge of the detailed physiology of
the synapses and circuits formed by these classified CBC types remains very limited. To address this
fundamental gap in our understanding of retinal processing, we developed a new experimental approach, using
dual pre- and post-synaptic patch-clamp recording from pairs of morphologically identified CBC types and
ganglion cell types in the whole-mount mouse retina in conjunction with two-photon optical recording and
targeted expression of genetically encoded glutamate and Ca sensors. This approach allowed us to correlate
the anatomical structure of each morphological CBC type with its intrinsic and receptive-field physiology and,
more importantly, to directly measure, at a millisecond resolution and under voltage-clamp condition, synaptic
transmission from identified CBC types to their postsynaptic targets in a structurally intact retina. Our preliminary
results revealed novel kinetic and circuit properties of CBC that suggested a new mechanism of synaptic
integration using both chemical and electrical synaptic transmission. Based on these preliminary results, we
propose a dual-mode synaptic mechanism by which CBCs transmit both a direct synaptic signal and a gap
junction-coupled network signal to their postsynaptic targets. This hypothesized mechanism will be tested
through the three Specific Aims. Aim 1, dual patch-clamp characterization of synaptic transmission and
functional connectivity between morphologically identified CBC types and a diffused ganglion cell type (W3) in
the whole-mount retina. Aim 2, understand the chemical and electrical synaptic interactions underlying signal
transmission from identified CBC types to W3 cells in the whole-mount retina. Aim 3, determine the functional
impact of different modes of CBC synaptic transmission on diffused and narrowly stratified postsynaptic target
cells. Results from this study are expected to provide novel insights into the synaptic mechanisms and functional
circuitry of cone bipolar cell types in the mammalian retina and shed light on chemical and electrical synaptic
integration in the CNS in general.

## Key facts

- **NIH application ID:** 10737233
- **Project number:** 1R01EY034652-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Z JIMMY ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $517,134
- **Award type:** 1
- **Project period:** 2023-09-30 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737233

## Citation

> US National Institutes of Health, RePORTER application 10737233, Synaptic mechanisms and circuitry of retinal interneurons (1R01EY034652-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10737233. Licensed CC0.

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