# Neuromuscular Control of Primate Eye Movements

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $197,004

## Abstract

Analyzing the visual world requires the meticulous coordination of both eyes, achieved by six muscles that
surround each eye. Controlled by motoneurons in the brainstem, these muscles move the eyes rapidly to acquire
targets (using saccades) or track them (smooth pursuit). The muscles also make slower adjustments to maintain
proper binocular alignment in depth (vergence) and keep the eyes still for target inspection (fixation). Common
visuomotor disorders such as strabismus result from abnormalities in this neuromuscular system. Current
treatments mitigate symptoms, but do not fix the underlying problems. To progress toward cures for the
disorders, we need to learn more about the details of the neuromuscular circuits. A longstanding curiosity about
extraocular muscle fibers has been that they come in two major types: multiply-innervated fibers (MIFs) that
receive numerous neuromuscular junctions along their entire length, and singly-innervated fibers (SIFs) that
receive a single band of neuromuscular junctions in their middle region. It was discovered recently in primates
that these two types of muscle fibers are supplied by distinct groups of motoneurons, revealing that the MIF vs.
SIF distinction extends to full motor units. Anatomical characteristics of MIFs and their motoneurons suggest
they control slow, binocular alignment (vergence and fixation) whereas SIFs and their motoneurons control
faster, targeting movements (saccades and smooth pursuit). The overall goal is to test this hypothesis of dual-
motor control of the eyes. This will be accomplished using linear array recordings and optogenetics to study MIF
and SIF motoneurons in behaving macaques. Pilot work showed that macaque extraocular motoneurons can be
virally transduced to express exogenous genes, setting the stage for the optogenetic approach. The first aim is
to achieve reliable, robust viral transduction and opsin expression in macaque motoneurons. Three viral vectors
will be injected into orbital muscles at varying volumes and titers. Consequent transgene expression in
motoneurons, along with any evidence of neurotoxicity, will be analyzed histologically up to 1 year post-injection
to determine optimal parameters. The second aim is to distinguish the functional roles of MIF and SIF
motoneurons. Exploiting the separate, colinear locations of MIF and SIF motoneurons in the primate oculomotor
nucleus, we will angle linear array electrodes to sample both populations simultaneously. Motoneuron activity
will be analyzed in relation to vergence, saccade, and smooth pursuit movements made by the macaques. MIF
motoneurons will be identified with in vivo optogenetic phototagging and histological analyses. The outcome of
the study will be to resolve whether MIF and SIF motor units constitute a dual-motor system for controlling the
eyes. If the MIF subsystem is specialized for binocular alignment, as predicted, it would be implicated as a locus
of disruption in strabismus, providing a spe...

## Key facts

- **NIH application ID:** 9919573
- **Project number:** 5R21EY030278-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Marc A Sommer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,004
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919573

## Citation

> US National Institutes of Health, RePORTER application 9919573, Neuromuscular Control of Primate Eye Movements (5R21EY030278-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9919573. Licensed CC0.

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