Dwarf cuttlefish: the mind-boggling species that unlocks boundless mysteries for neuroscientists!

The dwarf cuttlefish is a master of camouflage. In a matter of milliseconds, the animal can change both the pattern and texture of its skin to dynamically blend in with its surroundings. Camouflage is visually driven, and like its cousins ​​the squid and octopus, the cuttlefish controls its skin color with its brain. Neurons within the brain project their axons to the skin, where they control hundreds of thousands of cell pixels (chromatophores) to achieve color change.

When a cuttlefish is camouflaged, it reproduces what it sees on its skin. To achieve this, the cuttlefish must transform its visual input into a neural representation in the brain, and then recreate an analogue of that representation on its skin. The lab of Richard Axel, MD, wants to understand how cuttlefish accomplish this amazing feat. Understanding the way the visual world is represented in the brain, whether cephalopod or human, and how that representation leads to thoughts and behaviors, are among the most important issues in neuroscience.

To discover the neural basis of cuttlefish camouflage, members of Axel’s lab need to record the activity of neurons in relevant regions of the cuttlefish brain. However, to extract the most scientific value from those recordings, they also need a map of the brain, which has not been available. So the team embarked on a project to build a neuroanatomical atlas of the dwarf cuttlefish brain. His research paper describing the project appears online today at current biologywith a corresponding website, cuttlebase.org.

“One of my favorite approaches to learning about the brain is to study creatures that are highly specialized for particular behaviors or tasks, like bats that use echolocation to navigate, or birds that use impressive spatial memory to remember food locations. hidden.” said Tessa G. Montague, PhD, first author of the paper and a postdoctoral fellow in the lab of Richard Axel, MD, also an author of the paper.

“We hope and believe that our brain atlas will help the community learn more about the mechanisms that cuttlefish use to express themselves through their skin, and that this may give us insight into how any brain is capable of representing information,” he said. Dr. Montague.

It took a close and dedicated collaboration of experts in neuroscience, tissue imaging, computer programming, anatomy, and web design to build Cuttlebase. For the underlying foundation of the brain atlas, the team scanned the bodies and brains of four male and four female cuttlefish using magnetic resonance imaging (MRI), a diagnostic mainstay for clinicians. A deep learning algorithm, a type of artificial intelligence, helped separate the animals’ brains from the surrounding tissue, in the scan data.

Co-author Sabrina Gjerswold-Selleck, who recently completed a master’s degree at Columbia University and now works for Neuralink, said the team got off to a good start with the research because of related work she had done in co-author Jia Guo’s group at Columbia. with MRIs. of mice

“We developed a deep learning approach that was able to separate the brain-related data in each MRI from the data linked to other tissue types in these scans,” Gjerswold-Selleck said. “We were surprised at how well we were able to adapt the technique.”

Then, by comparing the MRI images to just a handful of labeled brain images from the 1960s, the researchers had to determine the boundaries of each dwarf cuttlefish brain lobe.. This was a monumental data analysis effort by six of the co-authors who put in hundreds of hours during the pandemic to delineate the eight cuttlefish data sets.

This resulted in hundreds of grayscale images with outlines of brain regions analogous to, for example, the outlines of states and counties in a multi-page atlas of the United States. To update their cuttlefish brain atlas to offer cellular resolution, equivalent to a detailed atlas showing every state road, hill, lake and river, the researchers turned to histological techniques, which reveal the microscopic structure of tissue. . This required the team’s biologists to meticulously section cuttlefish brains and then stain each one with colorful chemical tags that mark the locations of cells and parts of the brain, including neurons, glial cells and axons.

One of many views in the Cuttlebase web tool of the multi-lobed brain of the dwarf cuttlefish Sepia bandensis (Credit: Team Cuttlefish/Axis Lab/Zuckerman Institute)

Finally, after completing the histological atlas and annotating the eight cuttlefish MRIs, the researchers merged the eight brains into a single atlas. In all, they identified 32 lobes in dwarf cuttlefish, most of which they could relate to specific biological functions and behaviors, following classic studies from half a century ago. The two largest lobes, the optic lobes, process visual information from the animal’s fascinating eyes, for example. Motor neurons in the chromatophore lobes orchestrate the mechanisms of color change in the skin. A vertical lobe has been implicated in learning and memory.

While this analysis of the cuttlefish data is important in itself, “the main goal of the paper is to inform the visualization and research tool, Cuttlebase, and make it all freely available and easily accessible to everyone,” said the Dr Montague.

With intuitive ease, users can call up histology sections that specify different brain regions and nerves; a rotating and zoomable 3D model of the brain; and a 3D model of the cuttlefish’s 26 organs, including its three hearts, ink sac, beak, and nerves that transmit signals between the brain and its eight arms. All data in Cuttlebase is available for other researchers to develop in their labs. Explanations of the lobes of the brain and other user-friendly features provide learning resources for non-experts.

Co-authors Sukanya Aneja and Dana Elkis (the team’s web engineer and web designer, respectively) from New York University’s Interactive Telecommunications Program, who are also members of the Cuttlebase team, played lead roles in the development of the website. .

“We had a lot of back and forth on how to translate everything we had into a web-based experience that would appeal to both scientists and non-scientists,” Aneja said.

“We needed to combine video, images, the 3D template brain, illustrations, graphs and diagrams,” Elkis noted.

Co-author Isabelle Rieth, a graduate student in Northwestern University’s Interdepartmental Neuroscience Program and a former Cuttlebase team member, brought additional design skills to transform what otherwise would have been a black-and-white web experience into one filled with colors that help clarify what users see.

Despite how challenging and laborious the project has been for the collaborators, they can’t help but remain in love with the cuttlefish they work with and learn about.

“Cuttlefish are fascinating to watch,” said Dr. Montague. “When they camouflage or communicate with each other, they effectively reveal to you on their skin what they see and how they feel.”