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What's Your Fish Thinking?
by Carrie Arnold on 31 January 2013, 12:40 PM | 0 Comments

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Studying the links between brain and behavior may have just gotteneasier. For the first time, neuroscientists have found a way to watch

E NLAR GE IMAG E

neurons fire in an independently moving animal. Though the study wasdone in fish, it may hold clues to how the human brain works.
"This technique will really help us understand how we make sense of theworld and why we behave the way we do," says Martin Meyer, aneuroscientist at King's College London who was not involved in thework.
The study was carried out in zebrafish, a popular animal model because
they're small and easy to breed. More important, zebrafish larvae aretransparent, which gives scientists an advantage in identifying the neuralcircuits that make them tick. Yet, under a typical optical microscope,
neurons that are active and firing look much the same as their quieter
counterparts. To see what neurons are active and when, neuroscientists
have therefore developed a variety of indicators and dyes. For example,
when a neuron fires, it is flooded with calcium ions, which can causesome of the dyes to light up.

Glub, glub. Scientists developed a newtechnique that allows them to watch
what freely swimming zebrafish larvae(bottom left) are thinking as they watch
swimming paramecium (upper right).
Credit: Akira Muto/National Institute ofGenetics in Shizuoka, JapanStill, the approach has limitations. Traditionally, Meyer explains,researchers would immobilize the head or entire body of a zebrafish
larvae so that they could get a clearer picture of what was happening inside the brain. Even so, it was difficult tointerpret neural activity for just a few neurons and over a short period of time. Researchers needed a better way
to study the zebrafish brain in real time.
Enter Junichi Nakai of Saitama University's Brain
Science Institute in Japan. He and colleagues
selected a glowing marker known as green
fluorescent protein (GFP) and linked it to acompound that would light up in the presence oflarge amounts of calcium. The researchers theninserted the DNA that codes for this marker into theScienceNOW. ISSN 1947-8062

zebrafish genome, tying it to a specific protein only
found in neurons. This means that only actively
firing neurons would fluoresce, and scientists could
track neural activity without applying dye. Because
the signal was stronger and clearer, researchers
didn't have to immobilize the larvae.

genetically engineered zebrafish larvae hunting for

Eye on the ball. A close-up of the zebrafish optic tectum, which
tracks moving objects, as it watches moving paramecium.
Credit: Akira Muto/National Institute of Genetics in Shizuoka,
Japanfood. When the larvae see a swimming single-celledMore Science News Videos

To test the setup, Nakai and colleagues sent the

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What's Your Fish Thinking? - ScienceNOW

13/02/02 3:00

animal called a paramecium, they engage in what
animal behaviorists call a prey capture response:
They turn their heads toward the paramecium, swim
at it, and finally eat it.
Using their newly developed imaging system, Nakai
and colleagues associated the sight of moving
paramecium and prey capture behavior with theactivation of a group of neurons in the optic tectum,
the visual center of the zebrafish brain. The neurons
pulsed in tandem with the movements of theparamecium—a sudden dart of the one-celledorganism caused a bright flash of neural activity inthe zebrafish tectum (see videos). The tectum went
silent if the paramecium stilled. Only moving preyinterested the larvae, the team reports today inCurrent Biology. These particular neurons, Nakai
proposes, are part of a specific visual-motor
pathway that links the sight of moving prey with

Lighting up. Calcium signaling (red) in the zebrafish brain(purple, bottom) shows neural activity as the fish tracks aparamecium (right).
Credit: Akira Muto/National Institute of Genetics in Shizuoka,JapanMore Science News Videos

swimming behavior.
"It's a good proof of principle study," Meyer says. "The most important thing is that they showed [the techniqueworked] on freely behaving fish."
All animals, from zebrafish to humans, contain an optic tectum, which coordinates eye movement and theorganism's response to objects in their visual field. In humans, for example, the tectum helps us track a buzzing
mosquito so that we can take a swat at it. This means that the tectal activity in these transparent larvae could
have direct correlates in the brains of humans and other mammals, Nakai says. Scientists can also watch these
responses over time and compare brain activity with different stimuli.
The neurons in the larvae continuously make new GFP, which allows ongoing detection of neural activity. "Itmeans we can take the same measurements today, tomorrow, and the day after tomorrow," Nakai says. "Thistechnique makes long-term measurement possible." He hopes the approach will allow scientists to associate avariety of specific behavior patterns with specific neural circuits. That, in turn, could improve the development ofpsychiatric drugs, as scientists will more easily be able to tell if a particular drug has the desired effects on thebrain.

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