# Synaptic Architecture and Mechanisms of Direction Selectivity in Primate Retina

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $388,750

## Abstract

A major research challenge for neurobiology is to understand the neural mechanisms that give rise to an
extreme diversity of parallel visual pathways and ultimately the contributions that these pathways make to our
perception of motion, form and color. For motion perception the cell types, circuits and synaptic mechanisms
that mediate selectivity to the direction of moving stimuli have been intensively studied in the non-primate
mammal for decades and over a dozen distinct direction selective pathways are recognized in the mouse
retina together with growing evidence for similarly diverse underlying neural mechanisms. The great complexity
of the visual pathways found in the mouse is mirrored in the primate, yet surprisingly the abundant direction
selective ganglion cells have not been previously identified. The broad long-term objective of this new research
program is to elucidate for the first time the cell types, circuits, synaptic organization and underlying cellular
mechanisms for direction selectivity in the macaque monkey retina, as an ideal model for human visual
processing centered around the fovea. Our proposed research plan arises from a series of discoveries that
opens a door to the first detailed study of both the visual physiology and synaptic organization of direction
selective circuitry in the macaque retina. In preliminary studies we have identified the primate ON-OFF
direction selective ganglion cell as the recursive bistratified type and have developed new methods that permit
systematic targeting of this cell type for analysis. The synaptic physiology and directional tuning of this
ganglion cell type are the focus of Aim 1 where we test the hypothesis that directional selectivity in the primate
is radially aligned with respect to the fovea. Second, we have developed reliable methods for targeting the
starburst amacrine cell type, the key retinal interneuron in the direction selective circuit, for both physiological
analysis and connectomic circuit reconstruction for the first time. Preliminary data reveal novel features of
starburst receptive field structure, directional tuning and connectivity providing the focus for Aim 2 where we
test new hypotheses for the cellular origins of direction selectivity and its synaptic transfer to ganglion cells.
Finally, we have discovered direction selectivity in the poly-axonal spiking A1 amacrine cell type and evidence
for a functional link to ON-OFF direction selective ganglion cells. The focus of Aim 3 therefore is to test the
hypotheses that the A1 cells unique axonal component provides synaptic input to both starburst and ON-OFF
direction selective ganglion cells, and determine the role of the A1 cells unique dendro-axonal structure in
direction selectivity. In sum the broad aim is to characterize the directional tuning properties of these three cell
types, and to use connectomics for the first time to determine the underlying synaptic interactions that create
direction selectivity in the ...

## Key facts

- **NIH application ID:** 10749890
- **Project number:** 5R01EY032045-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** DENNIS MICHAEL DACEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749890

## Citation

> US National Institutes of Health, RePORTER application 10749890, Synaptic Architecture and Mechanisms of Direction Selectivity in Primate Retina (5R01EY032045-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10749890. Licensed CC0.

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