signaling

a-single-peptide-helps-starfish-get-rid-of-a-limb-when-attacked

A single peptide helps starfish get rid of a limb when attacked

biochemistry, Biology, muscles, Science, signaling, Starfish / /

You can have it —

A signaling molecule that’s so potent injected animals may drop more than one limb.

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A five-armed starfish, with orange and yellow colors, stretched out across a coral.

For many creatures, having a limb caught in a predator’s mouth is usually a death sentence. Not starfish, though—they can detach the limb and leave the predator something to chew on while they crawl away. But how can they pull this off?

Starfish and some other animals (including lizards and salamanders) are capable of autonomy (shedding a limb when attacked). The biology behind this phenomenon in starfish was largely unknown until now. An international team of researchers led by Maurice Elphick, professor of Animal Physiology and Neuroscience at Queen Mary University of London, have found that a neurohormone released by starfish is largely responsible for detaching limbs that end up in a predator’s jaws.

So how does this neurohormone (specifically a neuropeptide) let the starfish get away? When a starfish is under stress from a predatory attack, this hormone is secreted, stimulating a muscle at the base of the animal’s arm that allows the arm to break off.

The researchers confirmed this neuropeptide “acts as an autotomy-promoting factor in starfish and such it is the first neuropeptide to be identified as a regulator of autotomy in animals,” as they said in a study recently published in Current Biology.

Holding on

Elphick’s team studied how the neuropeptide known as ArSK/CCK1 facilitates autonomy in the European Starfish, Asterias rubens. ArSK/CCK1 is already known to inhibit feeding behavior in A. rubens by causing the stomach to contract, and muscle contraction plays a role in limb loss. The researchers found that its ability to trigger contractions goes beyond feeding.

Starfish underwent an experiment that simulated conditions where a predator’s jaw clamped down on one arm. Clamps were placed on one of three sections on a single arm, either on the end, middle, or at the site in the base where autotomy is known to occur, also known as the autotomy plane. The starfish were then suspended by these clamps above a glass bowl of seawater. During the first part of the experiment, the starfish were left to react naturally, but during the second part, they were injected with ArSK/CCK1.

Without the injection, autotomy was seen mostly in animals that had arms that were clamped closest to the autotomy plane. There was not nearly as much of a reaction from starfish when the arms were clamped in the middle or end.

In the second half of the experiment, the clamping used before was combined with an injection of ArSK/CCK1. For comparison, some were injected with the related neuropeptide ArSK/CCK2. A staggering 85 percent of ArSK/CCK1-injected animals that were clamped in the middle of the arm or closer to the autotomy plane exhibited autonomy, and some autotomized additional arms. This only happened in about 27 percent of those injected with ArSK/CCK2.

Letting go

While ArSK/CCK1 proved to be the most effective chemical trigger for autotomy, its activity in the autotomy plane depends on certain aspects of a starfish’s anatomy.

Like all echinoderms, starfish have endoskeletons built of tiny bones, or ossicles, linked by muscles and collagen fibers that allow the animals to change posture and move. Two exclusive features only found in the autotomy plane allow this structure to break. Under the skin of the autotomy plane, there is a region where bundles of collagen fibers are positioned far apart to make breakage easier. The second of these features is a band of muscle close to the region of collagen bundles. Known as the tourniquet muscle, this muscle is responsible for the constriction that allows an arm in danger to fall off.

Analyzing starfish arm tissue while it was undergoing autotomy gave the scientists a new perspective on this process. Right after a starfish has its arm seized by a predator,  ArSK/CCK1 tells nerves in the tourniquet muscle to start constricting in the region right by the autonomy plane. While this is happening, the collagen in the body wall in that region softens and breaks, and so do the muscles and ligaments that hold together ossicles. It is now thought that ArSK/CCK1 is also involved in the softening of this tissue that prepares it for breakage.

After starfish autotomize a limb, that limb eventually regenerates. The same happens in other animals that can use autotomy to their advantage (such as lizards, which also grow their tails back). In the future, finding out why some animals have the ability to regenerate may tell us why we either never evolved it or some of our ancestors lost the ability. Elphick acknowledged that there might still be other unidentified factors working together with ArSK/CCK1, but further insight could someday give us a clearer picture of this process.

“Autotomy is a key adaptation for survival that has evolved in several animal taxa,” the research team said in the same study, “[and] the findings of this study provide a seminal insight into the neural mechanisms that control this remarkable biological process,”

Current Biology, 2024.  DOI: 10.1016/j.cub.2024.08.003

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Human brain cells put much more energy into signaling

Biology, brain, frontal cortex, nerve cells, neurobiology, Science, signaling / /

Being human is hard —

Signaling molecules help modulate the brain’s overall activity.

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Image of a person staring pensively, with question marks drawn on the wall behind him.

Indian elephants have larger brains than we do (obviously). Mice have a higher brain-to-body mass ratio, and long-finned pilot whales have more neurons. So what makes humans—and more specifically, human brains—special?

As far as organs go, human brains certainly consume a ton of energy—almost 50 grams of sugar, or 12 lumps, every day. This is one of the highest energy demands relative to body metabolism known among species. But what uses up all of this energy? If the human brain is the predicted size and has the predicted number of neurons for a primate of its size, and each individual neuron uses comparable amounts of energy to those in other mammals, then its energy use shouldn’t be exceptional.

The cost of signaling

A group of neuroscientists speculated that maybe the amount of signaling that takes place within the human brain accounts for its heightened energy needs. A consequence of this would be that brain regions that are more highly connected and do more signaling will use more energy.

To test their hypothesis, the scientists started by imaging the brains of 30 healthy, right-handed volunteers between 20 and 50 years old. The imaging took place at two separate institutions, and it allowed the researchers to correlate a given brain region’s energy use (as measured by glucose metabolism) with its level of signaling and connectivity. They found that energy use and signaling scaled in tandem in all 30 brains. But certain regions stuck out. Signaling pathways in certain areas of the cortex—the front of the brain—require almost 70 percent more energy than those in sensory-motor regions.

The frontal cortex is one of the regions that expanded the most during human evolution. According to Robert Sapolsky, “What the prefrontal cortex is most about is making tough decisions in the face of temptation—gratification postponement, long-term planning, impulse control, emotional regulation. The PFC is essential for getting you to do the right thing when it is the harder thing to do.” This is the stuff that humans must constantly contend with. And energetically, it is extraordinarily costly.

Increased modulation is also key for cognition

It is not only signaling that takes energy; it is modulating that signaling, ensuring that it occurs at the appropriate levels and only at the appropriate times.

Using the Allen Human Brain Atlas, these researchers looked at gene activity in the frontal cortex. They found elevated activity of neuromodulators and their receptors. The authors note that “the human brain spends excessive energy on the long-lasting regulation of (fast) neurotransmission with (slow) neuromodulators such as serotonin, dopamine, or noradrenaline.” And also endogenous opiates. “This effect is more about setting the tone of general excitability than transferring individual bits of information,” they write.

Once they correlated energy use to signaling and slow-acting neuromodulation in the cortex, the last thing the scientists did was look at the Neurosynth project, which maps cognitive functions to brain regions. Lo and behold, the energy-hogging, highly connected, strongly modulated, and evolutionarily expanded parts of the cortex are the same ones involved in complex functions like memory processing, reading, and cognitive inhibition. This supports their idea of “an expensive signaling architecture being dedicated to human cognition.”

Science Advances, 2023.  DOI: 10.1126/sciadv.adi7632

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