# Dissecting the role of aggrecan and perineuronal nets in visual plasticity

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2024 · $461,687

## Abstract

Summary
Critical periods are time windows during development when experience-dependent plasticity is most robust.
The developing visual system in the premier model for studying how circuits modified by experience-dependent
plasticity are consolidated when a critical period closes. This model is clinically relevant because the closure of
the visual critical period is implicated in the pathophysiology of amblyopia, a childhood visual disorder
characterized by deficits in spatial vision including poor visual acuity and impaired depth perception. Effective
therapy is more difficult after the critical period closes because the brain is less plastic. In animal models of
amblyopia, monocular deprivation (MD) causes lasting deficits in ocular dominance (OD), binocular depth
perception, and visual acuity. The closure of the critical period is coincident with the maturation of perineuronal
nets in visual cortex, but how these extracellular structures may limit plasticity is not understood.
 In the proposed research, we will determine the role and cellular source of aggrecan, a principal
component of perineuronal nets, in closing the developmental critical period for plasticity in visual circuits. Our
hypothesis is that aggrecan operates outside of perineuronal nets to close the critical period. We will use a
combination of behavioral assays of vision, multi-unit electrophysiology, calcium imaging in vivo, and slice
electrophysiology in vitro, and genetic manipulations to determine how aggrecan regulates the plasticity of visual
circuits. This project will improve understanding of the mechanisms by which experience-dependent plasticity is
restricted in the maturing brain and may reveal new avenues for developing therapeutic approaches to treat
developmental visual disorders such as amblyopia and central visual impairment.

## Key facts

- **NIH application ID:** 10913638
- **Project number:** 5R01EY035138-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Aaron W McGee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $461,687
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913638

## Citation

> US National Institutes of Health, RePORTER application 10913638, Dissecting the role of aggrecan and perineuronal nets in visual plasticity (5R01EY035138-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10913638. Licensed CC0.

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