Move Over Zebrafish: Tiny transparent fish has smallest vertebrate brain, new model for neuroscience research

Written by Adam Tozer

October 17, 2018

• Tiny transparent fish Danionella translucida is just 12 mm in length
• Has a brain volume of 0.6 mm3 that contains around 650,000 neurons
• Genome editing techniques currently used in zebrafish work in Danionella 
• New model organism with promising features for the study of vertebrate neural circuits.

How does the brain integrate sensory information to then produce a motor output that performs a suitable behavioral response? -Understanding this question is one of the central goals of neuroscience.

Researchers across the world explore sensory integration and how it relates to decision making, motor output and behavioral responses in their model organisms on a daily basis. In doing this they hope to extrapolate their findings to understand the inner workings of our own brains.

The goal is to observe the activity of individual cells in real time in the animal’s brain whilst it performs a task or receives a stimulus.

Scientists have a comprehensive tool box of dyes and genetically-encoded reporters of membrane voltage that enable them to observe and probe the activity of multiple cells at once. As well as a suite of genetic tools they can use to activate or silence cells to manipulate their circuits of interest.

Despite these tools, there are lots of technical difficulties that need to be overcome by scientists to use their tools to achieve their goal.

IMAGING THROUGH THE SKULL

One notable difficulty in commonly used vertebrate animal models, such as zebrafish or rodents is the presence of the skull. Scientists can get around the issue of this occluding bone by making small windows they can image through or by using infrared imaging techniques to see through it.

The next limitation is the opacity and size of the brain tissue itself, rendering it difficult for scientists to measure more than the activity of a few hundred cells under their objectives, up to several hundred micrometres deep.

Deeper Understanding: Learn how MCI-Neuroscience’s technologies enable better resolution of neural activity at greater depth

Together this means it is very challenging for scientists to record the activity of individual cells within large circuits across the brain of an animal whilst it performs a task or carries out a behavior.

SWIMMING AROUND THE ISSUE

One approach to overcome the issue is to use smaller brained organisms, like nematode worms or fruit flies. Whilst they are excellent models for this type of research, their nervous systems are far smaller than vertebrate brains, which are more similar to our own.

The zebrafish Danio rerio is a well-used vertebrate model organism employed by many neuroscience labs across the world. Easy to care for and genetically tractable it has risen to prominence among molecular neurobiologist and behavioral neuroscientists alike. However, the issue of brain size and ease of imaging access to tissue still remains.

NEW FISH ON THE BLOCK

Now, Benjamin Judkewitz’s lab at Charite, Berlin, have established the tiny translucent fish Danionella translucida as a genetically tractable model for neuroscience research.

The smallest known vertebrate brain is optically transparent, genetically tractable and gives rise to remarkable behaviors. Credit: Benjamin Judkewitz, Twitter

The 12 mm long fish is optically transparent and importantly, has no roof to its skull, allowing for easy imaging of its tiny yet complete nervous system. Its brain volume is 0.6 mm3 and thought to contain around 650,000 neurons, an order of magnitude less than the total number of neurons in the zebrafish brain. Despite the small brain volume and number of neurons, Danionella performs complex behaviors such as schooling, shoaling, courtship and vocalizations.

Importantly, the group performed a proof-of-principle experiment where they expressed the calcium reporter GCamp6f in neurons. They were able to do this using genetic tools already developed for zebrafish research. Owing to the transparency of the fish, the group performed multiphoton imaging of individual neuron activity within the intact brain, through the skin.

They were also able to record the responses of single neurons to acoustic stimuli in vivo. Meaning they have all the tools they need to explore how the animal integrates auditory sensory information to inform its behavioral responses.

Taken together this work establishes Danionella translucida as a viable and easily accessible new model organism with promising features for the study of vertebrate neural circuits.

Discover: How MCI-Neuroscience are helping neuroscientists to study neuronal circuits

Reference:
Schulze, L., Henninger, J., Kadobianskyi, M., Chaigne, T., Faustino, A., & Hakiy, N. et al. (2018). Transparent Danionella translucida as a genetically tractable vertebrate brain model. Nature Methods. doi: 10.1038/s41592-018-0144-6

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