Researchers find new model of neuronal circuit provides insight on eye movement

(Image credit: Adobe Stock/peter verreussel)

A team of researchers at Weill Cornell Medicine and colleagues worked with week-old zebrafish to decode how the connections formed by a network of neurons in the brainstem guide the fishes’ gaze.

The study in Nature Neuroscience found that a simplified artificial circuit, based on the architecture of this neuronal system, can predict activity in the network. In addition to shedding light on how the brain handles short-term memory.¹

The findings could lead to novel approaches for treating eye movement disorders.

The researchers employed a range of advanced imaging techniques to identify the neurons involved in controlling gaze in young zebrafish and to map how these neurons are interconnected.

“Trying to understand how these short-term memory behaviors are generated at the level of neural mechanism is the core goal of the project,” said senior author Erme Aksay, PhD, an associate professor of physiology and biophysics at Weill Cornell Medicine, who led the study, together with Mark Goldman, PhD, at the University of California Davis and Sebastian Seung, PhD, at Princeton University.

To understand the contributions from circuit anatomy, Aksay and the research team examined larval zebrafish. By five days of age, these fishlets are swimming around and hunting prey, a skill that involves sustained visual attention.

The researchers discovered that the system is made up of two key feedback loops, each featuring three clusters of closely connected cells. Using this unique structure, they developed a computational model, which was able to accurately predict the activity patterns of the zebrafish circuit. They validated this model by comparing its predictions with physiological data.

Importantly for the research team, the brain region that controls the animals’ eye movement is structurally similar in fish and mammals. But the zebrafish system contains only 500 neurons.

“So, we can analyze the entire circuit—microscopically and functionally,” Aksay said. “That’s very difficult to do in other vertebrates.”

Moving forward, the researchers plan to investigate how the cells within each cluster contribute to the overall behavior of the circuit, and whether neurons in different clusters exhibit distinct genetic profiles. This insight could pave the way for targeted therapeutic interventions for eye movement disorders, by focusing on cells that may malfunction in these conditions.

This study was supported in part by the National Eye Institute R01 EY027036, R01 EY021581 and K99 EY027017; the National Institutes of Health grants from the National Institute of Neurological Disorders and Stroke R01 NS104926 and Brain initiative award 5U19NS104648; and the National Cancer Institute UH2 CA203710.¹

Reference

1. New model of neuronal circuit provides insight on eye movement | National Eye Institute. Nih.gov. Published November 22, 2024. Accessed November 25, 2024. https://www.nei.nih.gov/about/news-and-events/news/new-model-neuronal-circuit-provides-insight-eye-movement