Table of Contents
Zebrafish are a scientific wonder fish. They have Wolverine-like regeneration abilities and can regrow their spinal cord almost completely after damage. They also give scientists insight into some of the most primal states of the animal brain. Working with week-old zebrafish larvae, a team of scientists decoded how the connections made by a network of neurons in the brain stem guide where the fish looks. 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 handles short-term memory and could lead to new ways to treat eye movement disorders in humans. The findings are detailed in a study published Nov. 22 in the journal Nature Neuroscience. It also comes with a striking image taken with a microscope, with vibrant colors that show off the areas of the brain that control eye movements.
Skittish eyes and changing brain states
Animal brains are constantly recording a wide variety of sensory information about the environment, even if we are not aware of it. This data often changes from one moment to the next, and the brain is challenged to retain these quick, small pieces of information long enough to extract meaning from them. For example, it needs to connect what could be a series of mysterious sounds or allow an animal to keep its eyes focused on an area of interest such as prey or a potential threat lurking in the distance.
“Trying to understand how these short-term memory behaviors are generated at the level of the neural mechanism is the core goal of the project,” study co-author and Weill Cornell Medicine physiologist Emre Aksay. said in a statement.
[Related: How animals see the world, according to a new camera system.]
To decode the behavior taking place in these dynamic brain circuits, neuroscientists build mathematical models that 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 one preferred state until a new stimulus arrives. When that new stimulus appears, the circuit will enter a new activity state. In the visual-motor system, each of these states can store the memory of exactly where an animal should look.
However, questions remain about the rules and parameters that help set up that kind of switching system. One possibility comes down to the anatomy of the circuit–the connections formed between each neuron and how many connections they form. A second possibility is the physiological strength of those connections. This strength is determined by several factors, including the amount of neurotransmitter released, the type of receptors that receive the neurotransmitters, and the concentration of those receptors.
Building a neural circuit from scratch
In this new studythe team sought to understand the contributions of circuit anatomy to the visual system. When they are only five days old, zebrafish are already swimming around and hunting for prey. Searching for something to eat requires sustained visual attention, and the area of the brain 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 does about 100 billion neurons.
“So we can analyze the entire circuit, both microscopically and functionally,” says Aksay. “That’s very difficult to do in other vertebrates.”
[Related: Why do we send so many fish to space?]
While using several advanced imaging techniques, the team was able to… identified the neurons involved in zebrafish gaze control and how all these neurons are connected. They discovered that the system consists of two prominent feedback loops. Each of these feedback loops contains three clusters of closely connected 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 accurately predict activity patterns.
“I consider myself a physiologist first and foremost,” says Aksay. “So I was surprised how much of the circuit’s behavior we could predict based on the anatomical architecture alone.”
[Related: Scientists mapped every neuron of an adult animal’s brain for the first time.]
Future applications
In future studiesthe team wants to investigate how the cells in each cluster contribute to the behavior of the circuit and whether the neurons in the different clusters have specific genetic characteristics. This kind of data can help doctors therapeutically target the cells that may be malfunctioning in humans eye movement disorders. Strabismus occurs when both eyes are not in the same direction and results in “crossed eyes” or “walleye.” The disorder nystagmus presents as rapid, uncontrollable eye movements, also known as ‘dancing eyes’.
The findings also give scientists a way to unravel the more complex computer systems in the brain that rely on them short term memory, such as those who understand speech or decipher images.