# Molecular mechanisms underlying direction-selective circuit assembly and function in the mouse visual system

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $452,466

## Abstract

PROJECT SUMMARY
The elaboration of neural circuits involves a complex series of events, including neuronal differentiation,
settling of neurons in appropriate locations, neural process outgrowth and pathfinding, target selection,
synaptogenesis and synapse refinement. Development of direction-selective (DS) circuits in the mammalian
visual system relies on precise execution of each of these steps, however we are only beginning to understand
how these connections are established. The central goal of this proposal is to understand the molecular
mechanisms that allow components of DS circuits to mediate appropriate visual system responses to
image motion. DS responses depend critically on distinct classes of bipolar cells, starburst amacrine cells
(SACs), and direction-selective retinal ganglion cells (DSGCs). The development of these neurons, including
their differentiation and the regulation of their morphology and synaptic contacts, is integral to the generation of
functional DS circuitry. Here, we propose leveraging our recent gene profiling and additional Preliminary
Findings to address key unresolved questions in DS circuit wiring. Subtypes of DSGCs are tuned to motion in
distinct preferred directions, and this is due to differences in asymmetric wiring of SACs onto the dendrites of
these different DSGC subtypes; however, the underlying basis of this asymmetric SAC-DSGC wiring is
unknown. We have identified genes that are differentially expressed in subtypes of DSGCs that are
components of the Accessory Optic System (AOS): On-DSGCs (oDSGCs) that differ only in their preferred
directional preference–in this case for dorsal vs. ventral object motion. Analysis of these differentially
expressed (DE) genes has the potential to reveal underlying molecular mechanisms governing the
development of these oDSGCs and the synaptic wiring that determines their directional tuning, since the
central difference between dorsal-oDSGCs and ventral-oDSGCs is the polarity of their preferred directional
tuning. This proposal is focused on testing the hypothesis that differential gene expression in oDSGCs
of the accessory optic system (AOS) tuned to detect either upward or downward motion instructs the
development of functional DS circuits.

## Key facts

- **NIH application ID:** 10467036
- **Project number:** 5R01EY032095-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ALEX L KOLODKIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $452,466
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467036

## Citation

> US National Institutes of Health, RePORTER application 10467036, Molecular mechanisms underlying direction-selective circuit assembly and function in the mouse visual system (5R01EY032095-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467036. Licensed CC0.

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