CTHULHU STUDIES

Tracking a new path to octopus and squid sensing capabilities

Research reveals that the octopus explores the marine environment with sensing features that are evolutionarily related to human brain receptors

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

 

VIDEO: A CALIFORNIA TWO-SPOT OCTOPUS (OCTOPUS BIMACULOIDES) USES ITS ARM SUCKERS TO SECURE A FIDDLER CRAB. RESEARCH LED BY UC SAN DIEGO (HIBBS LAB) AND HARVARD UNIVERSITY (BELLONO LAB) HAS TRACED THE EVOLUTIONARY ADAPTATIONS OF OCTOPUS AND SQUID SENSING CAPABILITIES. THE STUDIES, FEATURED ON THE COVER OF THE APRIL 13, 2023 ISSUE OF NATURE, REVEAL EVOLUTIONARY LINKS TO HUMAN BRAIN RECEPTORS. view more 

CREDIT: ANIK GREARSON AND PETER KILIAN

Along their eight arms, octopuses have highly sensitive suckers that allow methodical explorations of the seafloor as they search for nourishment in a “taste by touch” approach. Squids, on the other hand, use a much different tactic to find their next meal: patiently hiding until they ambush their prey in swift bursts.

In a unique analysis that provides a glimpse into the origin stories of new animal traits, a pair of research studies led by University of California San Diego and Harvard University scientists has traced the evolutionary adaptations of octopus and squid sensing capabilities. The studies, featured on the cover of the April 13 issue of Nature, reveal evolutionary links to human brain receptors.

Researchers with Ryan Hibbs’ newly established laboratory in the School of Biological Sciences at UC San Diego (formerly based at the University of Texas Southwestern Medical Center) and Nicholas Bellono’s lab at Harvard analyzed octopuses and squids, animals known as cephalopods, through a comprehensive lens that spanned atomic-level protein structure to the entire functional organism. They focused on sensory receptors as a key site for evolutionary innovation at the crossroads of ecology, neural processing and behavior.

By looking at the way octopuses and squids sense their marine environments, the researchers discovered new sensory receptor families and determined how they drive distinct behaviors in the environment. With cryo-electron microscopy technology, which uses cryogenic temperatures to capture biological processes and structures in unique ways, they showed that adaptations can help propel new behaviors.

“Cephalopods are well known for their intricate sensory organs, elaborate nervous systems and sophisticated behaviors that are comparable to complex vertebrates, but with radically different organization,” said Hibbs, a professor in the Department of Neurobiology. Hibbs brings expertise on the structure of a family of proteins in humans that mediate communication between brain neurons and other areas such as between neurons and muscle cells. “Cephalopods provide striking examples of convergent and divergent evolution that can be leveraged to understand the molecular basis of novelty across levels of biological organization.”

In one Nature study, the research teams described for the first time the structure of an octopus chemotactile (meaning chemical and touch) receptor, which octopus arms use for taste-by-touch exploration. These chemotactile receptors are similar to human brain and muscle neurotransmitter receptors, but are adapted through evolution to help evaluate possible food sources in the marine environment.

“In octopus, we found that these chemotactile receptors physically contact surfaces to determine whether the animal should eat a potential food source or reject it,” said Hibbs. “Through its structure, we found that these receptors are activated by greasy molecules, including steroids similar to cholesterol. With evolutionary, biophysical and behavioral analyses, we showed how strikingly novel structural adaptations facilitate the receptor’s transition from an ancestral role in neurotransmission to a new function in contact-dependent chemosensation of greasy environmental chemicals.”

The second Nature study focused on squid and their wholly different ambush strategy for capturing food. The researchers combined genetics, physiology and behavioral experiments to discover a new class of ancient chemotactile receptors and determined one structure within the class. They also conducted an evolutionary analysis to link adaptations in squid receptors to more elaborate expansions in octopus. They were then able to place chemotactile and ancestral neurotransmitter receptors on an evolutionary timeline and described how evolutionary adaptations drove the development of new behaviors.

“We discovered a new family of cell surface receptors that offer a rare lens into the evolution of sensation because they represent the most recent and only functionally tractable transition from neurotransmitter to environmental receptors across the entire animal kingdom,” said Hibbs. “Our structures of these unique cephalopod receptors lay a foundation for the mechanistic understanding of major functional transitions in deep evolutionary time and the origin of biological novelty.”

Hibbs says the pair of new studies offers an excellent example of how curiosity in interesting creatures can lead to insights important for all of biology, namely how proteins—life’s building blocks—adapt to mediate new functions and behaviors.

“These studies are a great example of what being a scientist is all about—wonder, exploration and understanding how things work,” he said.

Octopus chemotactile receptor (VIDEO)

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Research led by UC San Diego (Hibbs Lab) and Harvard University (Bellono Lab) has traced the evolutionary adaptations of octopus and squid sensing capabilities. The research teams described for the first time the structure of an octopus chemotactile (meaning chemical and touch) receptor, which octopus arms use for taste-by-touch exploration. These chemotactile receptors are similar to human brain and muscle neurotransmitter receptors, but are adapted and evolved to help evaluate possible food sources in the marine environment.

CREDIT

Guipeun Kang

Research led by UC San Diego and Harvard has traced the evolutionary adaptations of octopus and squid sensing capabilities. The researchers describe for the first time the structure of an octopus chemotactile receptor, which octopus arms use for taste-by-touch exploration of the seafloor.

CREDIT

Anik Grearson and Peter Kilian

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JOURNAL

Nature

DOI

10.1038/s41586-023-05808-z 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Sensory specializations drive octopus and squid behaviour

ARTICLE PUBLICATION DATE

12-Apr-2023

#CTHULHU STUDIES

First gene knockout in cephalopod achieved 

CRISPR CRITTERS

by Marine Biological Laboratory

Longfin inshore squid (Doryteuthis pealeii) hatchlings. On the left is a control hatchling; note the black and reddish brown chromatophores evenly placed across its mantle, head and tentacles. In contrast, the embryo on the right was injected with CRISPR-Cas9 targeting a pigmentation gene (Tryptophan 2,3 Dioxygenase) before the first cell division ; it has very few pigmented chromatophores and light pink to red eyes. Credit: Karen Crawford

A team at the Marine Biological Laboratory (MBL) has achieved the first gene knockout in a cephalopod using the squid Doryteuthis pealeii, an exceptionally important research organism in biology for nearly a century. The milestone study, led by MBL Senior Scientist Joshua Rosenthal and MBL Whitman Scientist Karen Crawford, is reported in the July 30 issue of Current Biology.


The team used CRISPR-Cas9 genome editing to knock out a pigmentation gene in squid embryos, which eliminated pigmentation in the eye and in skin cells (chromatophores) with high efficiency.

"This is a critical first step toward the ability to knock out—and knock in—genes in cephalopods to address a host of biological questions," Rosenthal says.

Cephalopods (squid, octopus and cuttlefish) have the largest brain of all invertebrates, a distributed nervous system capable of instantaneous camouflage and sophisticated behaviors, a unique body plan, and the ability to extensively recode their own genetic information within messenger RNA, along with other distinctive features. These open many avenues for study and have applications in a wide range of fields, from evolution and development, to medicine, robotics, materials science, and artificial intelligence.

The ability to knock out a gene to test its function is an important step in developing cephalopods as genetically tractable organisms for biological research, augmenting the handful of species that currently dominate genetic studies, such as fruit flies, zebrafish, and mice.
Doryteuthis pealeii, often called the Woods Hole squid. Studies with D. pealeii have led to major advances in neurobiology, including description of the fundamental mechanisms of neurotransmission. The Marine Biological Laboratory collects D. pealeii from local waters for an international community of researchers. Credit: Roger Hanlon

It is also a necessary step toward having the capacity to knock in genes that facilitate research, such as genes that encode fluorescent proteins that can be imaged to track neural activity or other dynamic processes.

"CRISPR-Cas9 worked really well in Doryteuthis; it was surprisingly efficient," Rosenthal says. Much more challenging was delivering the CRISPR-Cas system into the one-celled squid embryo, which is surrounded by an exceedingly tough outer layer, and then raising the embryo through hatching. The team developed micro-scissors to clip the egg's surface and a beveled quartz needle to deliver the CRISPR-Cas9 reagents through the clip.

Studies with Doryteuthis pealeii have led to foundational advances in neurobiology, beginning with description of the action potential (nerve impulse) in the 1950s, a discovery for which Alan Hodgkin and Andrew Huxley became Nobel Prize laureates in 1963. For decades D. pealeii has drawn neurobiologists from all over the world to the MBL, which collects the squid from local waters.

Recently, Rosenthal and colleagues discovered extensive recoding of mRNA in the nervous system of Doryteuthis and other cephalopods. This research is under development for potential biomedical applications, such as pain management therapy.

D. pealeii is not, however, an ideal species to develop as a genetic research organism. It's big and takes up a lot of tank space plus, more importantly, no one has been able to culture it through multiple generations in the lab.

For these reasons, the MBL Cephalopod Program's next goal is to transfer the new knockout technology to a smaller cephalopod species, Euprymna berryi (the hummingbird bobtail squid), which is relatively easy to culture to make genetic strains.


Explore furtherThe mysterious, legendary giant squid's genome is revealed
More information: Current Biology (2020). DOI: 10.1016/j.cub.2020.06.099
Journal information: Current Biology


Provided by Marine Biological Laboratory

MISKATONIC U. CTHULHU STUDIES

Antarctic octopus DNA reveals ice sheet collapse closer than thought


Issam AHMED
Thu, 21 December 2023 

Today's ice sheet in Antarctic and that during the Last Interglacial when 

seaways allowed connections between octopus populations 

(Sophie STUBER)

Scientists investigating how Antarctica's ice sheets retreated in the deep past have turned to an innovative approach: studying the genes of octopuses that live in its chilly waters.

A new analysis published Thursday in Science finds that geographically-isolated populations of the eight-limbed sea creatures mated freely around 125,000 years ago, signaling an ice-free corridor during a period when global temperatures were similar to today.

The findings suggest the West Antarctic Ice Sheet (WAIS) is closer to collapse than previously thought, threatening 3.3-5 meters of long term sea level rise if the world is unable to hold human-caused warming to the 1.5 degrees Celsius target of the Paris Agreement, said the authors.


Lead author Sally Lau of James Cook University in Australia told AFP that as an evolutionary biologist focused on marine invertebrates, "I understand and then apply DNA and biology as a proxy of changes to Antarctica in the past."

Turquet's octopus made an ideal candidate for studying WAIS, she said, because the species is found all around the continent and fundamental information about it has already been answered by science, such as its 12-year-lifespan, and the fact it emerged some four million years ago.

About half-a-foot (15 centimeters) long excluding the arms and weighing around 1.3 pounds (600 grams), they lay relatively few, but large eggs on the bottom of the seafloor. This means parents must put significant effort into ensuring their offspring hatch -- a lifestyle that prevents them traveling too far away.

They are also limited by circular sea currents, or gyres, in some of their modern habitats.

- 'Tipping point close' -

By sequencing the DNA across genomes of 96 samples that were generally collected inadvertently as fishing bycatch and then left in museum storage over the course of 33 years, Lau and colleagues found evidence of trans-West Antarctic seaways that once connected the Weddell, Amundsen and Ross seas.

The history of genetic mixing indicated WAIS collapsed at two separate points -- first in the mid-Pliocene, 3-3.5 million years ago, which scientists were already confident about, and the last time in a period called the Last Interglacial, a warm spell from 129,000 to 116,000 years ago.

"This was the last time the planet was around 1.5 degrees warmer than pre-industrial levels," said Lau. Human activity, primarily burning fossil fuels, has so far raised global temperatures by 1.2C compared to the late 1700s.

There were a handful of studies prior to the new Science paper that also suggested WAIS collapsed some time in the past, but they were far from conclusive because of the comparatively lower resolution genetic and geological data.

"This study provides empirical evidence indicating that the WAIS collapsed when the global mean temperature was similar to that of today, suggesting that the tipping point of future WAIS collapse is close," the authors wrote.

Sea level rise of 3.3 meters would drastically alter the world map as we know it, submerging low-lying coastal areas everywhere.

Writing in an accompanying commentary piece, Andrea Dutton of the University of Wisconsin-Madison and Robert DeConto of the University of Massachusetts, Amherst described the new research as "pioneering," adding it posed intriguing questions about whether ancient history will be repeated.

They flagged however that several key questions remained unanswered -- such as whether the past ice sheet collapse was caused by rising temperatures alone, or whether other variables like changing ocean currents and complex interactions between ice and solid Earth were also at play.

It's also not clear whether the sea level rise would be drawn out over millennia or occur in more rapid jumps.

But uncertainties such as these can't be an excuse for inaction against climate change "and this latest piece of evidence from octopus DNA stacks one more card on an already unstable house of cards," they wrote.

ia/md

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 CTHULHU STUDIES

Octopus arms have segmented nervous systems to power extraordinary movements

The large nerve cord running down each octopus arm is separated into segments, giving it precise control over movements and creating a spatial map of its suckers.

University of Chicago

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Octopus arms move with incredible dexterity, bending, twisting, and curling with nearly infinite degrees of freedom.

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Credit: Cassady Olson

Octopus arms move with incredible dexterity, bending, twisting, and curling with nearly infinite degrees of freedom. New research from the University of Chicago revealed that the nervous system circuitry that controls arm movement in octopuses is segmented, giving these extraordinary creatures precise control across all eight arms and hundreds of suckers to explore their environment, grasp objects, and capture prey.

“If you're going to have a nervous system that's controlling such dynamic movement, that's a good way to set it up,” said Clifton Ragsdale, PhD, Professor of Neurobiology at UChicago and senior author of the study. “We think it’s a feature that specifically evolved in soft-bodied cephalopods with suckers to carry out these worm-like movements.”

The study, “Neuronal segmentation in cephalopod arms,” was published January 15, 2025, in Nature Communications.

Each octopus arm has a massive nervous system, with more neurons combined across the eight arms than in the animal’s brain. These neurons are concentrated in a large axial nerve cord (ANC), which snakes back and forth as it travels down the arm, every bend forming an enlargement over each sucker.

Cassady Olson, a graduate student in Computational Neuroscience who led the study, wanted to analyze the structure of the ANC and its connections to musculature in the arms of the California two-spot octopus (Octopus bimaculoides), a small species native to the Pacific Ocean off the coast of California. She and her co-author Grace Schulz, a graduate student in Development, Regeneration and Stem Cell Biology, were trying to look at thin, circular cross-sections of the arms under a microscope, but the samples kept falling off the slides. They tried lengthwise strips of the arms and had better luck, which led to an unexpected discovery.

Using cellular markers and imaging tools to trace the structure and connections from the ANC, they saw that neuronal cell bodies were packed into columns that formed segments, like a corrugated pipe. These segments are separated by gaps called septa, where nerves and blood vessels exit to nearby muscles. Nerves from multiple segments connect to different regions of muscles, suggesting the segments work together to control movement.

“Thinking about this from a modeling perspective, the best way to set up a control system for this very long, flexible arm would be to divide it into segments,” Olson said. “There has to be some sort of communication between the segments, which you can imagine would help smooth out the movements.”

Nerves for the suckers also exited from the ANC through these septa, systematically connecting to the outer edge of each sucker. This indicates that the nervous system sets up a spatial, or topographical, map of each sucker. Octopuses can move and change the shape of their suckers independently. The suckers are also packed with sensory receptors that allow the octopus to taste and smell things that they touch—like combining a hand with a tongue and a nose. The researchers believe the “suckeroptopy,” as they called the map, facilitates this complex sensory-motor ability.

To see if this kind of structure is common to other soft-bodied cephalopods, Olson also studied longfin inshore squid (Doryteuthis pealeii), which are common in the Atlantic Ocean. These squid have eight arms with muscles and suckers like an octopus, plus two tentacles. The tentacles have a long stalk with no suckers, with a club at the end that does have suckers. While hunting, the squid can shoot the tentacles out and grab prey with the sucker-equipped clubs.

Using the same process to study long strips of the squid tentacles, Olson saw that the ANC in the stalks with no suckers are not segmented, but the clubs at the end are segmented the same way as the octopus. This suggests that a segmented ANC is specifically built for controlling any type of dexterous, sucker-laden appendage in cephalopods. The squid tentacle clubs have fewer segments per sucker, however, likely because they do not use the suckers for sensation the same way octopuses do. Squid rely more on their vision to hunt in the open water, whereas octopuses prowl the ocean floor and use their sensitive arms as tools for exploration.

While octopuses and squid diverged from each other more than 270 million years ago, the commonalities in how they control parts of their appendages with suckers—and differences in the parts that don’t—show how evolution always manages to find the best solution.

“Organisms with these sucker-laden appendages that have worm-like movements need the right kind of nervous system,” Ragsdale said. “Different cephalopods have come up with a segmental structure, the details of which vary according to the demands of their environments and the pressures of hundreds of millions of years of evolution.”

University of Chicago

Octopus bimaculoides

Octopus bimaculoides

Octopus bimaculoides

Octopus bimaculoides

Octopus bimaculoides

Credit

Cassady Olson

Journal

Nature Communications

DOI

10.1038/s41467-024-55475-5 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Neuronal segmentation in cephalopod arms

Article Publication Date

15-Jan-2025

CTHULHU STUDIES

Unique features of octopus create ‘an entirely new way of designing a nervous system’

Peer-Reviewed Publication

UNIVERSITY OF CHICAGO MEDICAL CENTER

 

IMAGE: A HORIZONTAL A SLICE AT THE BASE OF THE ARMS (LABELED AS A) SHOWING THE ORAL INCS (LABELED AS O) CONVERGING AND CROSSING. view more 

CREDIT: KUUSPALU ET AL., CURRENT BIOLOGY, 2022

Octopuses are not much like humans — they are invertebrates with eight arms, and more closely related to clams and snails. Still, they have evolved complex nervous systems with as many neurons as in the brains of dogs, and are capable of a wide array of complicated behaviors. In the eyes of Melina Hale, PhD, and other researchers in the field, this means they provide a great opportunity to explore how alternative nervous system structures can serve the same basic functions of limb sensation and movement.

Now, in a new study published on November 28 in Current Biology, Hale, William Rainey Harper Professor of Organismal Biology and Vice Provost at UChicago, and her colleagues have described something new and totally unexpected about the octopus nervous system: a structure by which the intramuscular nerve cords (INCs), which help the animal sense its arm movement, connect arms on the opposite sides of the animal.

The startling discovery provides new insights into how invertebrate species have independently evolved complex nervous systems. It can also provide inspiration for robotic engineering, such as new autonomous underwater devices.

“In my lab, we study mechanosensation and proprioception — how the movement and positioning of limbs is sensed,” said Hale. “These INCs have long been thought to be proprioceptive, so they were an interesting target for helping to answer the kinds of questions our lab is asking. Up until now, there hasn’t been a lot of work done on them, but past experiments had indicated that they’re important for arm control.”

Thanks to the support for cephalopod research offered by the Marine Biological Laboratory, Hale and her team were able to use young octopuses for the study, which were small enough to allow the researchers to image the base of all eight arms at once. This let the team trace the INCs through the tissue to determine their path.

“These octopuses were about the size of a nickel or maybe a quarter, so it was a process to affix the specimens in the right orientation and to get the angle right during the sectioning [for imaging],” said Adam Kuuspalu, a Senior Research Analyst at UChicago and the lead author on the study.

Initially the team was studying the larger axial nerve cords in the arms, but began to notice that the INCs didn’t stop at the base of the arm, but rather continued out of the arm and into the body of the animal. Realizing that little work had been done to explore the anatomy of the INCs, they began to trace the nerves, expecting them to form a ring in the body of the octopus, similar to the axial nerve cords.

Through imaging, the team determined that in addition to running the length of each arm, at least two of the four INCs extend into the body of the octopus, where they bypass the two adjacent arms and merge with the INC of the third arm over. This pattern means that all the arms are connected symmetrically.

It was challenging, however, to determine how the pattern would hold in all eight arms. “As we were imaging, we realized, they’re not all coming together as we expected, they all seem to be going in different directions, and we were trying to figure out how if the pattern held for all of the arms, how would that work?” said Hale. “I even got out one of those children’s toys — a Spirograph — to play around with what it would look like, how it would all connect in the end. It took a lot of imaging and playing with drawings while we wracked our brains about what could be going on before it became clear how it all fits together.”

The results were not at all what the researchers expected to find.

“We think this is a new design for a limb-based nervous system,” said Hale. “We haven’t seen anything like this in other animals.”

The researchers don’t yet know what function this anatomical design might serve, but they have some ideas. “Some older papers have shared interesting insights,” said Hale. “One study from the 1950s showed that when you manipulate an arm on one side of the octopus with lesioned brain areas, you’ll see the arms responding on the other side. So it could be that these nerves allow for decentralized control of a reflexive response or behavior. That said, we also see that fibers go out from the nerve cords into the muscles all along their tracts, so they might also allow for a continuity of proprioceptive feedback and motor control along their lengths.”

The team is currently conducting experiments to see if they can gain insights into this question by parsing out the physiology of the INCs and their unique layout. They are also studying the nervous systems of other cephalopods, including squid and cuttlefish, to see if they share similar anatomy.

Ultimately, Hale believes that in addition to illuminating the unexpected ways an invertebrate species might design a nervous system, understanding these systems can aid in the development of new engineered technologies, such as robots.

“Octopuses can be a biological inspiration for the design of autonomous undersea devices,” said Hale. “Think about their arms — they can bend anywhere, not just at joints. They can twist, extend their arms, and operate their suckers, all independently. The function of an octopus arm is a lot more sophisticated than ours, so understanding how octopuses integrate sensory motor information and movement control can support the development of new technologies.”

The study, “Multiple nerve cords connect the arms of octopus providing alternative paths for inter-arm signaling,” was supported by the US Office of Naval Research (N00014-22-1-2208). Samantha Cody of the University of Chicago was also an author on the paper.

 

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About the University of Chicago Medicine & Biological Sciences

The University of Chicago Medicine, with a history dating back to 1927, is one of the nation’s leading academic health systems. It unites the missions of the University of Chicago Medical Center, Pritzker School of Medicine and the Biological Sciences Division. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine. Its main Hyde Park campus is home to the Center for Care and Discovery, Bernard Mitchell Hospital, Comer Children’s Hospital and the Duchossois Center for Advanced Medicine. It also has ambulatory facilities in Orland Park, South Loop, Homewood and River East as well as affiliations and partnerships that create a regional network of care. UChicago Medicine offers a full range of specialty-care services for adults and children through more than 40 institutes and centers including an NCI-designated Comprehensive Cancer Center. Together with Harvey-based Ingalls Memorial, UChicago Medicine has 1,296 licensed beds, nearly 1,300 attending physicians, over 2,800 nurses and about 970 residents and fellows.

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2022.11.007