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Understanding the Development of an Ancient Brain Circuit
A recent study reveals that an ancient brain circuit responsible for the eyes’ reflexive motion during body tilt develops during early life stages in animals.
Conducted by researchers at NYU Grossman School of Medicine, the study examines how vertebrates, including humans and diverse species from primitive fish to advanced mammals, stabilize their gaze while in motion. This stabilization is facilitated by a neural circuit that responds to changes in orientation detected by the vestibular system in the ears, leading to an immediate counter-movement of the eyes.
This mechanism, known as the vestibulo-ocular reflex, is essential for maintaining a stable perception of the environment. When this circuit malfunctions due to injury, stroke, or genetic conditions, individuals may experience disorienting sensations where their visual surroundings appear to move erratically during head or body movements. While adult vertebrates require sensory feedback from visual and balance organs to optimize this reflex, the authors found that newborns do not rely on such input for its maturation.
Published in the journal Science on January 2, the study involved experiments with zebrafish larvae, which exhibit a gaze stabilizing reflex analogous to that of humans. Zebrafish are particularly useful for these studies due to their transparent bodies, allowing researchers to directly observe the maturation of neurons responsible for the reflex as these fish learn to coordinate their eye movements with body orientation.
David Schoppik, PhD, the senior author of the study, emphasized the potential implications of understanding the development of vestibular reflexes, suggesting that insights from this research could lead to new strategies for addressing balance and eye movement pathologies.
Investigating Reflex Development
To challenge the long-held belief that visual feedback is necessary for tuning this reflex, the researchers designed an innovative apparatus to elicit the reflex in zebrafish that had been blind since birth. Observations showed that these blind fish exhibited similar abilities to counter-rotate their eyes in response to body tilts as their sighted counterparts.
While prior research indicated that sensory feedback assists animals in mastering their movements within their surroundings, this new research suggests that tuning of the vestibulo-ocular reflex might only occur after the initial maturation phase. Additionally, the study revealed that the reflex circuit develops independently of input from a gravity-sensing organ, the utricle.
Identifying Maturation Factors
Given that the vestibulo-ocular reflex matures without sensory feedback, the research team speculated that the slowest-moving element of the brain circuit might dictate the overall development of the reflex. To pinpoint this lagging component, the researchers tracked the responses of neurons as they stimulated zebrafish with rapid body tilts.
They discovered that both central and motor neurons in the circuit demonstrated mature responses prior to the complete development of the reflex. Surprisingly, the slowest-maturing segment was not located in the brain, as previously thought, but rather at the neuromuscular junction—the site where motor neurons communicate with muscle cells responsible for eye movement. Further investigations indicated that the maturation rate of the junction corresponded with the improvement in the fish’s ability to counter-rotate their eyes.
Dr. Schoppik’s team plans to explore the implications of these findings for human health. Their ongoing research aims to understand how disruptions in the development of motor neurons and neuromuscular junctions can lead to ocular motor disorders, including strabismus, commonly referred to as lazy eye or crossed eyes.
Moreover, situated just before the motor neurons in this reflex circuit are interneurons that process incoming sensory information, integrating visual data with input from balance organs. Dr. Schoppik is also pursuing grants to investigate how these interneurons function when balance circuits develop, aiming to support the approximately five percent of children in the U.S. who face balance-related challenges.
As Dr. Paige Leary, the study’s lead author, mentioned, understanding the foundational principles of vestibular circuit emergence is vital for addressing not only balance disorders but also developmental brain disorders more broadly.
Co-authors of the study included researchers from the departments of Otolaryngology — Head & Neck Surgery, Neuroscience & Physiology, and the Neuroscience Institute at NYU Langone Health, highlighting a collaborative effort supported by several grants from the National Institutes of Health and the National Science Foundation.
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