# Structure and Function of Mammalian Ganglion Cells

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $485,675

## Abstract

The retina is unequaled as a model system for linking genes to cells and synapses to brain mechanisms
underlying purposive behaviors. >30 types of retinal ganglion cells (RGCs) convey specialized output signals
to the visual centers of the brain. Each type is distinctive in form, response properties, brain connections, and
functional roles. A key step in understanding the mechanistic basis of these parallel visual representations is
to work out the ‘wiring diagram’ linking each type to bipolar and amacrine cells. Almost nothing is known about
such wiring for the great majority of RGC types. Serial electron microscopic (SEM) reconstruction provides a
unprecedented opportunity to map these synaptic circuits in all their richness, and my lab has been engaged
for several years in an ambitious project to do just that. Here we propose a series of projects grounded in this
approach that should fundamentally augment our ability to explain how the stimulus selectivity of individual
RGC types arises from their connectivity patterns.
 Our first goal is to provide the first definitive accounting of the connectivity between all the known types of
bipolars cells and virtually every major type of RGC. Bipolar cells relay photoreceptor signals to the inner
retina, but there are about 15 distinct bipolar types differing in response polarity, cone contributions, and
temporal kinetics. Using an SEM volume in which we have already reconstructed the majority of RGC and
bipolar cells, we will generate a comprehensive, unbiased bipolar-to-RGC connectome.
 We will then combine SEM and functional studies to probe two sets of RGC circuits inferred from the
literature and our preliminary data. In the first of these subprojects, we will probe specialized bipolar and
amacrine networks that permit ipRGCs to encode luminance and which appear to provide a route by which
ipRGCs can exert inhibitory control over the primary rod pathway. Because ipRGCs provide a stable
representation of luminance, we surmise that this network represents a key system for shutting the rod system
down under bright light conditions, a form of network light adaptation. In the second subproject, we will probe
two aspects of the retinal circuits underlying image stabilization, traceable to a different RGC type: the ON
direction-selective (ON-DS) cells. We will test the idea that the distinctive speed tuning of these cells is
attributable to one or more specific amacrine-cell types that veto the response to rapid motion. We will test the
hypothesis that speed tuning varies topographically in these cells to match the geometry of optic flow produced
by self-motion. We will also assess the asymmetric connectivity from starburst amacrine cells to ON-DS cells
to test the hypothesis that such asymmetry (like the DS it produces) also varies topographically and is fully
congruent with that of ON-OFF DS cells.

## Key facts

- **NIH application ID:** 10004635
- **Project number:** 5R01EY012793-20
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** David M. Berson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,675
- **Award type:** 5
- **Project period:** 2000-02-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004635

## Citation

> US National Institutes of Health, RePORTER application 10004635, Structure and Function of Mammalian Ganglion Cells (5R01EY012793-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10004635. Licensed CC0.

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