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Ophthalmology Times: July/August 2025
Volume50
Issue 4

Reflex for stabilizing vision develops without sensory input

Key Takeaways

  • Sensory input is unnecessary for the maturation of the vestibulo-ocular reflex circuit in newborns, unlike in adult vertebrates.
  • Zebrafish studies showed that visual information is dispensable for the development of the vestibulo-ocular reflex.
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Maturing of the vestibulo-ocular reflex is independent of sensory input

(Image Credit: AdobeStock/Khan)

(Image Credit: AdobeStock/Khan)

Signals that originate from the vestibular system of the inner ear stabilize the retinal images as the body moves and the head tilts. The brain circuit in the so-called vestibulo-ocular reflex facilitates an individual’s stable perception of his or her surroundings. This phenomenon happens early in development. However, investigators who conducted a recent study identified an unexpected finding: Sensory input was not necessary for maturation of the reflex circuit in newborns. This is in contrast to what happens in adult vertebrates, in which the reflex circuit and other brain circuits are tuned by feedback from the vision and balance organs.

David Schoppik, PhD, senior author, and colleagues conducted a study in which they went back to the beginning to determine the origins of the vestibular reflex. The investigators published their most recent findings in Science.1

Discovering how vestibular reflexes come to be may help us find new ways to counter pathologies affecting balance or eye movements,” said Schoppik, associate professor in the Department of Otolaryngology—Head and Neck Surgery, the Department of Neuroscience and Physiology, and the Neuroscience Institute at NYU Langone Health, New York.

Zebrafish study

Figure 1:  A zebrafish swims, it uses a brain circuit that turns any shifts in orientation sensed by the balance system into an instant counterrotation of the eyes. The body rotates, but the orientation of the eyes stays the same. A new study reveals what controls the maturation pace of this reflex in newborn animals, with implications for balance and eye movement disorders.
Figure 1: A zebrafish swims, it uses a brain circuit that turns any shifts in orientation sensed by the balance system into an instant counterrotation of the eyes. The body rotates, but the orientation of the eyes stays the same. A new study reveals what controls the maturation pace of this reflex in newborn animals, with implications for balance and eye movement disorders.

Paige Leary, PhD, first author of the study, and colleagues studied an archetypal sensorimotor circuit that stabilizes gaze in the larval zebrafish, which they described as a powerful model to uncover neural mechanisms of sensorimotor behavior2 due to its relative simplicity and the high conservation of this circuit across vertebrates.3 They used the transparent zebrafish, which has a similar gaze-stabilizing reflex to that in humans, to determine the role of external sensory feedback in the development of the vestibulo-ocular reflex circuit (Figure 1 and Figure 2).

Figure 2: The zebrafish eye grows considerably larger from 3 days old (top) to 15 days old (bottom), with related changes in brain circuitry that enable the zebrafish to stabilize its gaze. A new study reveals what controls the maturation pace of this circuit in newborn animals, with implications for balance and eye movement disorders.

(Images courtesy of NYU Langone Health)
Figure 2: The zebrafish eye grows considerably larger from 3 days old (top) to 15 days old (bottom), with related changes in brain circuitry that enable the zebrafish to stabilize its gaze. A new study reveals what controls the maturation pace of this circuit in newborn animals, with implications for balance and eye movement disorders.
(Images courtesy of NYU Langone Health)

The vestibulo-ocular reflex circuit consists of sensory afferents, central interneurons, and motor neurons that together transform head/body tilts into counter-rotatory eye movements.4 When mature, this feed-forward circuit generates eye movements matching the head/body velocity, minimizing retinal slip and stabilizing gaze. In vertebrates, both gaze stabilization and vestibulo-ocular reflex circuit components mature during early development.5 In contrast to the normal functioning of the circuit, when it is interrupted as the result of trauma, stroke, or a genetic condition, a person may feel like the world bounces around every time their head or body moves, Leary explained.

In the zebrafish experiment, the fish were immobilized with their eye freed and tilted nose up/nose down on a rotating platform in complete darkness. They were rotated +15° (nose up), held for 7.5 seconds, and then returned. The right eye rotated clockwise, or down, in response.

The first question researchers addressed was how the gaze stabilization behavior would develop in a blind subset of fish compared with their sighted siblings. The authors found the development between the 2 groups was comparable, meaning, according to the researchers, that visual information was dispensable for the development of the vestibulo-ocular reflex.

Although previous research established that sensory input helps animals learn to move properly in their environment, the study under discussion suggested that such tuning of the vestibulo-ocular reflex comes into play only after the reflex has fully matured.

This all happens because the central and motor neurons in the circuit showed mature responses before the reflex had finished developing. Consequently, they pointed out, the slowest part of the circuit to mature could not be in the brain, as has been long assumed, but instead is at the neuromuscular junction, that is, the signaling space between motor neurons and the muscle cells that move the eye.

“Larvae without vestibular sensory experience, but whose neuromuscular junction was mature, had a strong vestibulo-ocular reflex. Development of the neuromuscular junction, and not sensory experience, determines the rate of maturation of an ancient behavior,” Leary and colleagues reported.

The next step for the researchers is a funded study of the newly detailed circuit in human disorders. Their ongoing work explores how failures of motor neurons and neuromuscular junction development lead to ocular motor system disorders, including strabismus.

David Schoppik, PhD
E: david.schoppik@nyulangone.org
Paige Leary, PhD
E: paige.leary@nyulangone.org
Both researchers are from the Department of Otolaryngology—Head and Neck Surgery, the Department of Neuroscience and Physiology, and the Neuroscience Institute at NYU Langone Health, New York.

Neither researcher has a financial interest in this subject matter. The study was supported by the National Institutes of Health through National Institute on Deafness and Other Communication Disorders grants R01DC017489 and F31DC020910, and by the National Institute for Neurological Disorders and Stroke grant F99N.

References
  1. Leary P, Bellegarda C, Quainoo C, Goldblatt D, Rosti B, Schoppik D. Sensation is dispensable for the maturation of the vestibulo-ocular reflex. Science. 2025;387(6729):85-90. doi:10.1126/science.adr9982
  2. Goldberg JM, Wilson VJ, Cullen KE, et al. The Vestibular System: A Sixth Sense. Oxford University Press; 2012.
  3. Straka H, Baker R. Vestibular blueprint in early vertebrates. Front Neural Circuits. 2013;7:182. doi:10.3389/fncir.2013.00182
  4. Szentagothai J. The elementary vestibulo-ocular reflex arc. J Neurophysiol. 1950;13(6):395-407. doi:10.1152/jn.1950.13.6.395
  5. Beraneck M, Lambert FM, Sadeghi SG. Functional development of the vestibular system: sensorimotor pathways for stabilization of gaze and posture. In: Romand R, Varela-Nieto I, eds. Development of Auditory and Vestibular Systems. 4th ed. Elsevier; 2014:449-487.

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