Mapping the changing gaze of fishlets

Zebrafish are a scientific wonder fish. They have Wolverine-like regeneration abilities– and can almost completely regenerate their spinal cord after injury. It also gives scientists insight into some of the the most primitive states of the animal brain. While working with week-old zebrafish larvae, a team of scientists decoded how the connections made by a network of neurons in the brainstem guide where the fish points. They also created a simplified artificial circuit that can predict visual movement and activity in the animal’s brain. This discovery sheds light on how the brain manages short-term memory and could lead to some new ways to treat eye movement disorders in humans. The findings are detailed in a study published on November 22 in the journal Nature Neuroscience. It also comes with a stunning image taken under a microscope, with vibrant colors that highlight the regions of the brain that control eye movements.

Moving eyes and changing brain states

Animal brains are constantly receiving a wide variety of sensory information about the environment, even when we are not consciously aware of it. This data often changes from moment to moment, and the brain faces the challenge of retaining these quick, small nuggets of information long enough to make sense of it. For example, they have to connect what might be a set of mysterious sounds or enable an animal keep your eyes focused on an area of interest like prey or a potential threat lurking in the distance.

“Trying to understand how these short-term memory behaviors are generated at the neural mechanism level is the main goal of the project,” study co-author and Weill Cornell Medicine physiologist Emre Aksay. said in a statement.

To decode the behavior that occurs in these dynamic brain circuits, neuroscientists building mathematical models which describe how the state of a system changes over time and where that current state determines the future states of the circuit according to a set of rules. One of the brain’s short-term memory circuits will remain in a single preferred state until a new stimulus appears. When that new stimulus occurs, the circuit will settle into a new state of activity. In the visual-motor system, each of these states can store memory of exactly where an animal should look.

However, questions remain about rules and parameters that help configure this type of change system. One possibility boils down to circuit anatomy– the connections that form between each neuron and how many connections they form. A second possibility is the physiological strength of these connections. This potency is determined by several factors, including the amount of neurotransmitter that is released, the type of receptors that capture the neurotransmitters, and the concentration of those receptors.

Building a neural circuit from scratch

In this new studythe team sought to understand what contributions circuit anatomy made to the visual system. When they are only five days old, zebra “fishlets” are already swimming and hunting for prey. I’m looking for something to eat it involves sustained visual attention, and the brain region that controls eye movement is structurally similar in both fish and mammals. However, the zebrafish system only contains 500 neurons. By comparison, the human brain has about 100 billion neurons.

“So we can look at the entire circuit — microscopically and functionally,” Aksay said. “It’s very hard to do in other vertebrates.”

While using several advanced imaging techniques, the team identified the neurons involved in zebrafish gaze control and how all these neurons are linked together. They found that the system consists of two prominent feedback loops. Each of these feedback loops contains three closely related groups of cells. Using this setup, they built a computer model of what happens in this part of the zebrafish brain.

When the team compared the artificial network they built with physiological data from a real zebrafish, they found that their fake network could accurately predict activity patterns.

“I consider myself a physiologist first and foremost,” Aksay said. “So I was surprised how much of the circuit’s behavior we could predict just from the anatomical architecture.”

Future applications

In future studiesthe team plans to explore how the cells in each group contribute to the circuit’s behavior and whether neurons in the different groups have specific genetic signatures. This type of data could help clinicians therapeutically target cells that might be malfunctioning in humans. eye movement disorders. Strabismus occurs when both eyes do not line up in the same direction and results in “cross eyes” or “eyes. Nystagmus disorder presents as rapid, uncontrollable eye movements, sometimes called “dancing eyes.”

The findings offer scientists a way to unravel the more complex computational systems in the brain that rely on short term memory, like those who understand speech or decipher images.