In a groundbreaking study involving week-old zebrafish larvae, a team of researchers from Weill Cornell Medicine and other institutions has made significant strides in understanding how a network of neurons in the brainstem helps control eye movement. This research, which was published in Nature Neuroscience, shows that a simplified artificial circuit based on the architecture of the neuronal system can effectively predict activity in this network. The implications of these findings extend beyond a better understanding of short-term memory to potential new treatments for eye movement disorders.
Our brain is constantly processing a vast amount of sensory information about our surroundings. For us to make sense of our environment, our brain must retain this information long enough to form a complete image. This involves linking together words in a sentence or directing our gaze towards an area of interest. This study, led by Dr. Emre Aksay, associate professor of physiology and biophysics at Weill Cornell Medicine, along with Dr. Mark Goldman at the University of California Davis and Dr. Sebastian Seung at Princeton University, aims to better understand the neural mechanisms behind these short-term memory behaviors.
To investigate this, the researchers utilized the tools of dynamical systems, involving mathematical models that describe how a system changes over time based on a set of rules. In a short-term memory circuit, a new stimulus can cause the system to shift to a new activity state. In the visual-motor system, each of these states can remember where an animal should be looking. The team theorized that the system’s architecture, such as the connections each neuron forms and their physiological strength, could set up this type of dynamical system.
Using larval zebrafish, which are able to swim and hunt prey by five days old, the researchers examined the brain region controlling eye movement. The team discovered that this region is structurally similar in fish and mammals, but the zebrafish system contains only 500 neurons, making it easier to analyze the entire circuit.
The researchers identified the neurons involved in controlling gaze direction and determined how they are connected. They found that the system consists of two main feedback loops, each containing three tightly connected cell clusters. Using this information, they created a computational model and found that their artificial network could accurately predict the activity patterns of the zebrafish circuit.
Looking ahead, the researchers plan to study how the cells in each cluster contribute to the circuit’s behavior and whether the neurons in the different clusters have distinct genetic signatures. This insight could potentially allow clinicians to target specific cells that may malfunction in eye movement disorders. The findings also offer a blueprint for understanding more complex computational systems in the brain that rely on short-term memory, such as those involved in deciphering visual scenes or understanding speech.
This study was supported by various grants from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the National Eye Institute, and the National Cancer Institute.
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