Sensory Biology Around the Animal Kingdom

The comb jelly’s single statocyst sits at the animal’s uppermost tip, under a transparent dome of fused cilia. A mass of cells called lithocytes, each containing a large, membrane-bound concretion of minerals, forms a statolith, which sits atop four columns called balancers, each made up of 150–200 sensory cilia. As the organism tilts, the statolith falls towards the Earth’s core, bending the balancers. Each balancer is linked to two rows of the ctenophore’s eight comb plates, from which extend hundreds of thousands of cilia that beat together as a unit to propel the animal. As the balancers bend, they adjust the frequency of ciliary beating in their associated comb plates. “They’re the pacemakers for the beating of the locomotor cilia,” says Sidney Tamm, a researcher at the Marine Biological Laboratory in Woods Hole, Massachusetts, who has detailed the structure and function of the ctenophore statocyst (Biol Bull, 227:7-18, 2014; Biol Bull, 229:173-84, 2015).

Sensing gravity’s pull and the subsequent ciliary response is entirely mechanical, Tamm notes—no nerves are involved in ctenophore statocyst function. Most other animals with statocyst sensing, on the other hand, do employ a nervous system. Statocysts exist in diverse invertebrate species, from flatworms to bivalves to cephalopods. Although the details of the statocyst’s architecture vary greatly across these different groups, it is generally a balloon-shape structure with a statolith in the center and sensory hair cells around the perimeter. As the statolith, which can be cell-based as in the ctenophore or a noncellular mineralized mass, falls against one side of the sac, it triggers those hair cells to initiate a nervous impulse that travels to the brain.

The complexity of the statocyst system appears to correlate with the complexity of a species’ movement and behavior, says Heike Neumeister, a researcher at the City University of New York. Squids and octopuses, which move rapidly around in three-dimensional space, for example, have highly adapted equilibrium receptor organs. Likewise, the nautilus, whose relatives were among the first animals to leave the bottom of the ocean and begin swimming and employing buoyancy, has a fairly advanced system. Each of its two statocysts is able to detect not only gravity, like the ctenophore’s, but angular accelerations as well, like those of octopuses, squids, and cuttlefishes (Phil Trans R Soc Lond B, 352:1565-88, 1997). “[Nautilus] statocysts are an intermediate state of evolution between simpler mollusks and modern cephalopods,” says Neumeister.

These sensory systems may be damaged by the man-made noise now resonating throughout the world’s oceans. Michel André, a bioacoustics researcher at the Polytechnic University of Catalonia in Barcelona, Spain, started looking into the effects of noise pollution on cephalopods after the number of giant squid washing ashore along the west coast of Spain shot up in 2001 and then again in 2003. “The postmortem analysis couldn’t reveal the causes of the death,” recalls André. Nearby, however, researchers were conducting ocean seismic surveys, using pulses of high-intensity, low-frequency sound to map the ocean floor. Although, these animals don’t have ears, André and others wondered if that noise might be affecting the squids’ sense of balance.

Sure enough, exposing squid, octopuses, and cuttlefish to low-frequency sound, which caused the animals’ whole bodies to vibrate, universally resulted in damage to their statocysts. Hair cells were ruptured or missing; the statocysts themselves sometimes had lesions or holes; even the associated nerve fibers suffered damage. As a result, the animals became disoriented, often floating to the water’s surface (Front Ecol Environ, doi:10.1890/100124, 2011). “They eventually died because they were not eating,” says André. “I don’t think that [anyone thought] that animals who could not hear would be suffering from acoustic trauma. . . . This is something we have to be concerned about.”

—Jef Akst

Feeling the Flow

© CLAUS LUNAU/SCIENCE SOURCELight, sound, and odors travel through water very differently than they do in air. Accordingly, aquatic animals have sensory systems tuned to their fluid medium—most notably, the lateral line system. Observable as distinct pores that run along the flanks and dot the heads of more than 30,000 fish species, the lateral line is composed of mechanoreceptors called neuromasts—clusters of hair cells not unlike those found in the mammalian ear and vestibular system—that relay information about the velocity and acceleration of water flow.

“If you live underwater, the water is often moving with respect to your body, and it’s carrying the environment with it,” says University of California, Irvine, biologist Matt McHenry, who studies the lateral line sense in fish. “To have some sense of where it’s going and how fast it’s going seems pretty fundamental. It makes a lot of sense that they would be tuned in to flow.” Despite more than 100 years of research on the lateral line, however, many questions remain about its structure and function, how the sense relays information to the nervous system, and how it affects fish behavior.

NEUROMASTS: Clusters of hair cells project from the surface of a larval zebrafish’s skin to sense the water’s movement. (Cupula has been removed.)JURGEN BERGER/MAX PLANCK INSTITUTE FOR DEVELOPMENTAL BIOLOGYTransparent zebrafish larvae, whose surface lateral line structures can be observed without the need for dissection, are starting to yield answers. Using a high-power microscope, Jimmy Liao of the University of Florida’s Whitney Laboratory for Marine Science and his colleagues attach tiny glass probes to individual neuromasts and stimulate the mechanoreceptors with controlled vibrations. “We’re able to tickle an individual neuromast and record from the neuron that innervates that specific cluster,” he says. With this system, Liao’s team has found that a neuromast’s response to different water velocities depends on its position in space (J Neurophysiol, 112:1329-39, 2014). “If you bend [a neuromast] halfway and then give it a velocity, that’s very different than just giving it the velocity in its normal configuration,” Liao says.

Liao and his collaborators have also determined that the sensors stimulate sensory neurons in a nonlinear fashion—that is, with increasing velocity, the nervous response only increases up to a certain point, then levels off (J Neurophysiol, 113:657-68, 2015). And the researchers have traced the nervous connections from neuromasts found on the flank of a fish’s body to specific locations within the posterior lateral line ganglion, a group of nerve cells outside the brain. Tail neuromasts are connected to afferent neurons found in the center of the ganglion, Liao says, while neuromasts closer to the head contact neurons on its periphery.

When it comes to the specific role of lateral line sensing in fish behavior, however, the research is still somewhat murky. “We have a very crude understanding for what behaviors depend on this sense,” says McHenry. “At a receptor level, I think we have a pretty good handle for what kind of information they’re extracting, but in real-world applications it’s not clear why that’s useful a lot of the time.”

HAIRLINE: Modified epithelial cells called hair cells—similar to those in the mammalian inner ear—are the work horses of the lateral line in fishes. Hair cells connect to afferent neurons and are grouped together into structures called neuromasts whose hairs are covered by a jelly-like secretion called the cupula. When moving water or vibrations trigger neuromasts, which sit inside pores on the head, body, and tail of the fish, hair cells stimulate neurons to relay information about velocity or acceleration to sensory ganglia distributed through the fish’s body.© LAURIE O'KEEFEOne challenge is isolating sensory information detected by the lateral line from information detected by other fish senses, specifically vision, says Sheryl Coombs, an emeritus professor at Bowling Green State University who has spent decades studying the links between the lateral line sense and fish behavior. “Most behaviors rely on animals integrating information across the senses,” she says. “It’s difficult sometimes to pick apart the role of the lateral line because the senses act together in complementary ways, often.”

To get around this problem, Coombs has studied nocturnal fish and species that live in complete darkness, such as the Mexican blind cave fish (Astyanax mexicanus), which often lacks eyes altogether. In this species, Coombs has found that the fish may use their lateral line sense to construct rudimentary maps of their surroundings. “They’re basically ‘listening’—for lack of a better word—to their own flow field that they create by moving through the water,” she says. “They create the flow, and then they’re listening to distortions in that flow created by the presence of the obstacle. It’s sort of analogous to echolocation in the sense that animals are producing a sound and they’re listening to how the sound bounces back.”

—Bob Grant

Magnetoreception

Mollusks, insects, birds, and some mammals are able to sense Earth’s magnetic field, but how they do so remains a mystery. In the last couple of decades, “most of the research [has focused] on proteins and genetics in the various animals, speculating on possible means of magnetoreception,” says Roswitha Wiltschko, who—along with her husband, Wolfgang Wiltschko—ran a magnetoreception lab at Goethe University Frankfurt, Germany, until she retired in 2012.

Although the details are still unclear, most magnetoreception researchers have converged upon two key mechanisms: one based on magnetite, an iron oxide found in magnetotactic bacteria, mollusk teeth, and bird beaks; and the other on cryptochromes, blue-light photoreceptors first identified in Arabidopsis that are known to mediate a variety of light-related responses in plants and animals.

Once we have found magnetoreception structures reliably, we can start trying to understand how they convert the magnetic field into a neural response.—Roswitha Winklhofer
 Goethe University Frankfurt

In 2001, Michael Winklhofer, then at Ludwig Maximilian University of Munich, and colleagues reported their identification of magnetite in the beaks of homing pigeons (Eur J Mineral, 13:659-69). A year earlier, Klaus Schulten of the University of Illinois at Urbana-Champaign and colleagues proposed that cryptochromes in the bird eye might also play a role in avian magnetoreception (Biophys J, 78:707-18, 2000). Specifically, the authors suggested that photoactivated cryptochromes form a pair of charged radicals, which are thought to affect a bird’s sensitivity to light. Schulten and his colleagues speculated that Earth’s magnetic fields could somehow affect these cryptochrome reactions in a way that would alter the bird’s visual system, providing information about its orientation. (See “A Sense of Mystery,” The Scientist, August 2013.)

MAGNETO: There are two prominent ideas for how some animals are able to detect the Earth’s magnetic fields. Diverse species have magnetite-containing cells, which are thought to be innervated and contain surface ion channels that are physically pulled open as magnetic fields tug on magnetite tethered to the cell membrane or the channel itself (top). Birds and possibly other animals also appear to “see” magnetic fields through the visual system. Proteins called cryptochromes that reside in the eye’s cones can form a pair of radicals (unpaired electrons), whose spin is affected by magnetic fields and may affect the animal’s sensitivity to light (above).

© LAURIE O'KEFFE

Over the years, support for this idea has emerged. In 2007, Henrik Mouritsen of the University of Oldenburg, Germany, and colleagues showed that blue light–exposed avian cryptochrome 1a indeed forms long-lived radical pairs (PLOS ONE, 2:e1106). And this April, Peter Hore of the University of Oxford and colleagues published a computer-based modeling study showing that light-dependent chemical reactions in cryptochrome proteins in the eyes of migratory birds could “account for the high precision with which birds are able to detect the direction of the Earth’s magnetic field,” the authors wrote (PNAS, 113:4634-39, 2016).

Birds seem to use both the magnetite and the radical pair/cryptochrome–based mechanisms. Cryptochrome-based orientation has also been reported in Drosophila and cockroaches, and researchers have found evidence of magnetite-based navigation in animals from mollusks to honeybees. And there may be other components of magnetoreception still to discover, as scientists continue their search for magnetic sensory structures across the animal kingdom. Late last year, for example, biophysicist Can Xie of Peking University in Beijing and colleagues identified a Drosophila protein, dubbed MagR, that—when bound to photosensitive Cry—has a permanent magnetic moment, the researchers reported, meaning it spontaneously aligns with magnetic fields (Nat Mater, 15:217-26, 2015). The MagR/Cry complex, the researchers noted, exhibits properties of both magnetite-based and photochemical magnetoreception. (See “Biological Compass,” The Scientist, November 2015). The study was met with skepticism, however, and the results have yet to be independently verified.

In addition to mechanism, questions remain about the function of magnetoreceptive capabilities. “Once we have found [magnetoreception structures] reliably, we can start trying to understand how they convert the magnetic field into a neural response, and at the brain level, how are the single responses processed and integrated with other navigational information to tell the animal where it is and where to go,” says Winklhofer.

In the mid-1990s, for example, Wiltschko and her husband Wolfgang demonstrated that migratory birds called silvereyes (Zosterops lateralis) reacted to a strong magnetic pulse by shifting their orientations 90° clockwise, returning to their original headings around a week later (Experientia, 50:697-700, 1994). Magnetic field manipulations can also affect Drosophila navigation, John Phillips, now of Virginia Tech, has shown (J Comp Physiol A, 172:303-08, 1993). And Richard Holland, now of Bangor University, U.K., and colleagues showed in the mid-2000s that experimentally shifting the Earth’s magnetic field altered homing behavior in Eptesicus fuscus bats (Nature, 444:702, 2006).

“Some animals use their magnetic sense for long-distance navigation, some for magnetic alignment or orientation, and some animals may have the capability to sense the magnetic field but do nothing,” says Xie. Or, at least, nothing that has yet been recognized by researchers.

—Tracy Vence

Thermoreception

HEAT SENSE: Pit organs consist of a large, hollow, air-filled outer chamber and a smaller inner chamber separated by a membrane embedded with heat-sensitive receptors. The receptors are innervated by the trigeminal ganglia (TG), which transmit the infrared signals to the brain.© LAURIE O'KEEFEMany animals are able to sense heat in the environment, but vampire bats and several types of snakes are the only vertebrates known to have highly specialized systems for doing so. Humans and other mammals sense external temperature with heat-sensitive nerve fibers, but pit vipers, boa constrictors, and pythons have evolved organs in their faces that the animals use to detect infrared (IR) energy emitted by prey and to select ecological niches. And vampire bats have IR receptors on their noses that let them home in on the most blood-laden veins in their prey.

“Infrared sense is basically a souped-up [version] of thermoreception in humans,” says David Julius, a professor and chair of the physiology department at the University of California, San Francisco (UCSF), who studies this sense in snakes. The difference is, snakes and vampire bats “have a very specialized anatomical apparatus to measure heat,” he says.

These IR-sensing apparatuses, known as pit organs, have evolved at least twice in the snake world—once in the ancient family that includes pythons and boas (family Boidae) and once in the pit vipers (subfamily Crotalinae), which includes rattlesnakes. Pythons and boas have three or more simple pits between scales on their upper and sometimes lower lips; each pit consists of a membrane that is lined with heat-sensitive receptors innervated by the trigeminal nerve. Pit vipers, by contrast, typically have one large, deep pit on either side of their heads, and the structure is more complex, lined with a richly vascularized membrane covering an air-filled chamber that directs heat onto the IR-sensitive tissue. This geometry maximizes heat absorption, Julius notes, and also ensures efficient cooling of the pit, which reduces thermal afterimages.

In 2010, Julius and Elena Gracheva, now at Yale University, identified the heat-sensitive ion channel TRPA1 (transient receptor potential cation channel A1) that triggers the trigeminal nerve signal in both groups of snakes (Nature, 464:1006-11). The same channels in humans are activated by chemical irritants such as mustard oil or by acid, and the resulting signal is similar to those produced by wounds on the skin, Gracheva says. In snakes, these channels have mutated to become sensitive to heat as well.

Vampire bats—which, true to their name, feed on the blood of other creatures—are the only mammals known to have a highly developed infrared sense. Like snakes, the bats have an innervated epithelial pit, which is located in a membrane on the bats’ noses. In 2011, Julius, Gracheva, and their colleagues identified the key heat-sensitive ion channel in vampire bats as TRPV1 (Nature, 476:88-91). In humans, this channel is normally triggered by temperatures above 43 °C, but in the bats, it is activated at 30 °C, the researchers found.

More than 30 years ago biologists Peter Hartline, now of New England Biolabs in Ipswich, Massachusetts, and Eric Newman, now at the University of Minnesota, found that information from the snake pit organ activates a brain region called the optic tectum (known in mammals as the superior colliculus), which is known to process visual input (Science, 213:789-91, 1981). The pit organ appears to act like a pinhole camera for infrared light, producing an IR image, Newman says. However, it’s impossible to know whether snakes actually “see” in infrared.

“Unfortunately we don’t have a sensory map [of the brain] in snakes or vampire bats,” Gracheva agrees. “I don’t think we have enough data to say [these animals] can superimpose a sensory picture onto the visual picture, though it definitely would make sense.”

—Tanya Lewis

Electroreception

Apullae of Lorenzini openings in great white shark skin © GARY BELL/OCEANWIDEIMAGESSharks and other fish are well known for their ability to detect electric fields, with some species able to sense fields as weak as a few nanovolts per centimeter—several million times more sensitive than humans. But it turns out that they aren’t the only ones. In recent years, evidence for electroreception has been accumulating all over the animal kingdom: in monotremes (such as the platypus), crayfish, dolphins, and, most recently, bees.

“The number of taxa that are now effectively known to detect weak electric fields is increasing,” says Shaun Collin of the University of Western Australia, “although some of these we don’t know very much about yet, and for some we only have evidence of a behavioral response.”

ELECTRIC SLIDE: Sharks and other cartilaginous fish have highly specialized electroreceptive organs called the ampullae of Lorenzini. These bundles of sensory cells, situated at the end of jelly-filled pores in the skin, detect electric fields in the water surrounding the fish and send signals to the brain.© LAURIE O'KEEFEFirst formally described in the middle of the last century in weakly electric fish (J Exp Biol, 35:451-86, 1958), electroreception operates most effectively over less than half a meter in water—a more conductive medium than air. The sense is most frequently employed by aquatic or semi-aquatic animals to find prey in environments where other senses are less reliable—in murky or turbid water, for example, or where food can bury itself in sediment. Such “electrolocation” is usually passive, relying on bioelectric fields generated by the nerves and muscles of other animals, but some species, such as knifefish, measure distortions in electric fields that they themselves generate.

Researchers have also documented other functions of electroreception. “Especially in the stingray family, it is used in social communication,” says Collin. “The opposite sex can use it to assess whether there’s a potential for mating, and discriminate that opportunity from something that could turn into predation.” And some baby sharks appear to use electroreception for predator aversion. According to research by Collin’s group, electric fields trigger a “freeze” response in bamboo sharks while they’re still in egg sacs (PLOS ONE, doi:10.1371/journal.pone.0052551, 2013).

Electroreception is thought to be an ancestral trait among vertebrates that has subsequently been lost from several lineages (including the amniotes—the group comprising reptiles, birds, and mammals), and then re-evolved independently at least twice in teleost fish and once in monotremes. In 2011, researchers added cetaceans to that list, after discovering electroreception in the Guiana dolphin, a resident of murky coastal waters around South America that evolved its electroreceptors from what used to be whiskers (Proc R Soc B, doi:10.1098/rspb.2011.1127).

Most electroreceptors consist of modified hair cells with voltage-sensitive protein channels, arranged in bundles that activate nerves leading to the brain. “The classic example is the ampullae of Lorenzini,” says Collin. Described in 1678 by Italian anatomist Stefano Lorenzini, ampullae are extensions of the lateral line system that are present in dense clusters over the heads of cartilaginous fish such as sharks and rays. Each ampulla consists of a bundle of electrosensory cells at the end of a pore filled with a hydrogel that was recently shown to have the highest reported proton conductivity of any known biological material (Sci Advances, 2:e1600112, 2016).

But pinning down how any of these receptors operate at a molecular level remains a challenge, notes Clare Baker, a neuroscientist at the University of Cambridge. “We hardly know anything about the specific genes involved, or the genetic basis for building electroreceptors in the embryo,” she says, adding that the major animal models in fish and amphibians—zebrafish Danio rerio and frog genus Xenopus—both belong to lineages that have lost electroreception altogether.

Baker’s group has adopted the paddlefish, a relative of the sturgeon, as a model organism. Electrosensitivity in these animals, as in other primitive vertebrates such as the axolotl, depends on modified hair cells that develop as part of the ancestral lateral line system and are homologous to the ampullary organs of sharks. Fate-mapping experiments in these species have identified candidate genes for electroreceptor development (Evol Dev, 14:277-85, 2012), and Baker says future work will use gene-editing technologies such as CRISPR-Cas9 to get a better grip on these genes’ functions.

Meanwhile, the field is continuing to uncover surprises. In 2013, research from Daniel Robert’s group at the University of Bristol showed that bumblebees are capable of detecting the weak electric fields generated by flowers, and use this information to discriminate between food sources of differing quality (Science, 340:66-69). And earlier this year, the same researchers identified bees’ electrosensors as tiny hairs that move in the presence of electric fields (PNAS, 113:7261-65, 2016). “Electroreception provides another source of information,” says Robert, who suspects that a flower’s electric field may indicate to bees when nectar and pollen are available. “They’re really good at learning where the resources are.”

For Collin, the Bristol team’s findings are indicative of how much more there is still to discover about electroreception. Even in large clades such as reptiles and birds, “there is circumstantial evidence that they might have electroreception, but there hasn’t been anything concrete,” he says. “There may well still be examples of functions we don’t even know about.”

—Catherine Offord