The non-model organism “renaissance” has arrived

Rodents can’t vomit. This makes it “challenging” to study the sensation of nausea, says Chuchu Zhang. The neurons that control nausea are still mostly unknown. “We have no idea how it works,” Zhang says.

So, in her quest to understand “how our body copes with noxious cues” we ingest, Zhang turned away from rodent models to the shrew—which are similarly easy to house and care for in the lab, she says. Importantly, shrews exhibit nausea and vomiting behaviors in many of the same conditions that people do. “Cancer chemotherapy drugs and bacterial toxins that cause food poisoning, all of this will cause the shrew to vomit,” she says.

Zhang is setting up a colony of Asian house shrews at her newly opened lab. Her next step is to target cell types of interest, including neurons in the brainstem and vagal ganglia, using single-cell RNA- and ATAC-sequencing—methods to measure gene expression levels and identify accessible regions of the genome, respectively.

During the nightless summers on the Arctic tundra, male pectoral sandpipers rarely sleep. Instead, they spend every possible moment trying to mate.

Pulling those all-nighters has benefits: The birds that sleep the least produce the most chicks, according to a 2012 study. But at the same time, the brain requires sleep to normalize the synaptic connections that have been strengthening all day, says study investigator John Lesku. How can male sandpipers forgo sleep for days and even weeks?

Lesku and his colleagues tracked the sleep patterns of 300 males this past mating season, and they are now comparing synapse strength in the brains of the eight birds that slept the most versus the eight that slept the least.

“If they have a neurological cost to sustained wakefulness, then they should have stronger synapses than males that are sleeping more,” he says, because they are not experiencing the synapse-weakening that is thought to occur during sleep. Alternatively, the birds may have a way to reduce the strength of those synapses without sleep.

“Do they have a mechanism for not suffering the fate of sleep deprivation, at least in the brain?” Lesku wonders.

Locusts easily succumb to peer pressure. A variety of grasshopper, these insects typically live solitary lives. But when they encounter their fellow locusts in large numbers, their antisocial behavior undergoes a dramatic change: They begin to clump together, swarm and reproduce more.

Neuroscientists can replicate this lifestyle shift in the lab by moving previously isolated locusts into a group with hundreds of others. “Locusts can change their physiology and behavior very quickly depending on the environment and population density,” says Einat Couzin-Fuchs. “It’s a nice model to understand plasticity.”

The neurotransmitter serotonin drives the locusts’ behavioral transition; and simultaneous brain modifications, such as the enlargement of specific brain regions, may facilitate this phenotypic plasticity, studies show.

Crowding changes the locusts’ living circumstances, such as their food availability, so they need to adapt accordingly. For example, it changes the balance of excitation and inhibition in their olfactory system, enhancing food detection, Couzin-Fuchs recently found. And in the realm of insects, “[locusts] are big and relatively robust,” she says. These physiologically flexible insects can help to reveal how animals adapt to better cope with changing environments, she adds.

Researchers often select animal models that mirror something they want to understand about humans: prairie voles’ instinct to pair bond, for instance, or how songbirds learn their tunes. But that is not how Elly Tanaka chose her species of interest: axolotls, a freshwater species of salamander endemic to Mexico.

Tanaka was initially drawn to amphibians in general because they have embryos that develop from large, accessible eggs, making it easy to examine their early-life development, she says. When she learned that axolotls in particular can also regenerate much of their body—including their brain—she decided that she wanted to get to the root of that unusual capability.

“We’re studying this animal because it’s different from other animals,” Tanaka says.

To help her on her quest, she and her colleagues have developed genetic tools to explore and manipulate axolotl development, identified regulatory elements that become active in the animals’ cells during regeneration, and produced a single-cell atlas of the axolotl telencephalon, which forms part of the forebrain.

Her team is also investigating what the species, which is one of the closest representatives of the first animals to walk on four legs, can reveal about how tetrapods evolved, Tanaka says.

“It is the simplest brain that controls four-legged motion,” she adds. “It’s a valuable model for us to understand what’s the minimal circuit that controls a tetrapod.”

Every September and October, a single generation of monarch butterflies migrates thousands of miles from Canada and the northern United States down to Mexico, where they roost until March. They have never made this journey before, yet thanks to the circadian clock located in their antennae, they know when to leave and how to get there. “You can imagine why I’m working on something like that,” says Christine Merlin. “It’s a mind-blowing phenomenon.”

In her lab, Merlin hand-raises a colony of about 1,500 butterflies each month to breed genetic knockouts. Her location in College Station, Texas, also grants her access to wild monarchs as they flit down to Mexico.

The monarchs use the sun and the earth’s magnetic field as compasses to maintain their southern heading. Their circadian clocks enable them to compensate for the sun’s constantly changing location. When March rolls around, the migrating generation lays eggs, and the next few generations slowly make their way back up north.

In addition to their migratory feat, monarchs have a “simplified version of the mammalian clock,” Merlin says. The clock consists of transcription factors that can repress themselves and thus turn gene expression on and off in a rhythmic cycle. The most prominent circadian clock model, Drosophila melanogaster, does not contain every mammalian repressor, and in the mammalian clock, the repressors are duplicated and triplicated, which is more difficult to study, she says. “So we can use the monarch as a model system to understand the mechanisms that keep this clock ticking.”

Lab mice can live for about two and a half years, a zebrafish for as long as six. And those relatively long lifespans make studying the brain’s aging process in these species tricky, says Anne Brunet: By the time a researcher can engineer animals with a certain genetic change, watch them age and adapt the next experiment accordingly, the outcomes take nearly a decade to observe.

But Brunet has found a solution: the African turquoise killifish, a species that lives only four to six months. “You can test many genes at once [in the killifish]—in part because it’s more short-lived than mice,” she says, but also because the fish are less expensive to maintain and have more progeny than lab mice.

Over the past two decades, Brunet and her colleagues have developed new techniques for studying the killifish, including species-specific tools for genetic engineering. They have also discovered changes that occur during the natural aging process. For example, an RNA-binding protein called DDX5 aggregates in the aging killifish brain—and in the brains of aging mice—where it acts in a prion-like manner, seeding the formation of other aggregates, she and her team reported in June. Such a “snowball effect” may contribute to other aging effects, she says.

Whether these findings hold up in people remains to be seen. The killifish “is never going to be able to substitute for humans,” Brunet acknowledges. “But of course the human is not a model organism. So it’s nice to have model systems that are iterative and scalable—to be able to test ideas that then could be applicable to longer-lived organisms.”

Naked mole rats lead a bustling, if unilluminated, life. The members of a colony—a queen, one to three breeding males, and dozens of nonreproductive workers—constantly bump into each other in the dark in their underground tunnels as they work together to dig, move food and care for their young.

“They’re arguably the most social animals in the entire mammalian kingdom,” says Ishmail Abdus-Saboor. Yet the mole rats don’t recognize one another like other mammals do: They are blind and don’t hear or smell very well. They do, however, have an extraordinary sense of touch—and for that reason, “we think that the mole rats can teach us how you can use touch as a way to communicate with others,” Abdus-Saboor says.

The mole rats’ somatosensory cortex proportionally takes up three times as much cortical space as the same region in other mammals, Abdus-Saboor notes. Plus, their entire bodies are covered in whiskers so sensitive that the animal can respond to a single deflection, he adds. Face touches may help the animals recognize and remember one another, Abdus-Saboor and his team reported in a preprint in February. And because they are hairless, apart from their whiskers, the touch neurons innervating their skin may more accurately model tactile sensations in people than the neurons innervating the furry skin of a mouse.

Abdus-Saboor started the colony in his lab about three years ago and says he hopes the mole rat work will intersect with his team’s ongoing mouse studies. Findings from the “extreme case” of the naked mole rat that are corroborated by mouse experiments could yield insights into more general somatosensation principles, he says.

Biology is the study of life, but some researchers are drawn toward death.

“Death is really what unites all living things,” says Z Yan Wang, “and the octopus is, I think, one of the best models to study the role of the nervous system in death.”

Both male and female octopuses die after they reproduce—something that has been known for hundreds of years, but “we just haven’t had the tools to be able to get a mechanism” for why this happens, Wang says. Unraveling the neuroendocrine controls of this senescence process is multi-pronged work that involves combining behavior, genomics and transcriptomics, she adds.

One specific part of the octopus brain she has focused on is the optic gland, which controls the self-destruct system. The functional analog of this gland in vertebrates is the anterior pituitary gland, but it doesn’t make any steroid hormones like the optic gland does in octopuses, she says. Transcriptomics of the optic glands in female California two-spot octopuses at different stages of the death process revealed “it wasn’t just one hormone” controlling this end-of-life behavior, but “a whole complex orchestra of molecular changes that [are] happening at the level of the nervous system and of the body,” Wang says.

She sees the genomic and transcriptomic datasets as “treasure chests” that still hold more secrets. So far, what she knows is “a cool story,” she says, “but I really hope it’s just the first chapter of a really long book.”

Bats are naturals at hearing, and their auditory system is one of their most important assets. They emit vocalizations that can land on other bats’ ears to communicate or that can bounce off surfaces to help them navigate. The bat “lives for that,” says Julio Hechavarría.

Thanks to their natural ability, “you don’t lose time training” bats on hearing-related tasks, he adds.

Their auditory system occupies a large portion of their brain, “so if you want to record from auditory neurons, you just have to stick an electrode, and essentially everything is going to be auditory,” Hechavarría says.

He says he can even predict what a bat is hearing just by measuring its brain activity. And activity in the frontal cortex and the cerebellum can predict the sound bats produce or have just produced, he and his colleagues reported in a study last month.

Some neurons in the auditory cortex of bats integrate information from both echolocation and communication sounds, responding to two different acoustic modalities, other work shows. And neurons in the brainstem enable bats to detect deviations from expected auditory patterns, his team found in a study published in February.

Thanks to these ingrained traits, bats are well-suited for studying how the brain perceives and produces complex natural behaviors, Hechavarría says. “Bats have something that is very unique about them, and that’s that you can link them very well to neuroethology.”

Many animals, including mice, perform ritualistic social behaviors and establish hierarchies both in the wild and in the lab. But tiny cichlid fish offer researchers an easier way to study complex social interactions, says Tessa Solomon-Lane. “They will affiliate, court, be aggressive, parent,” she says. “You can create an entire social microcosm at a density that the animal naturally lives at and show the behaviors they naturally do in the wild.”

Early-life social interactions among African cichlids, whether in pairs or in larger groups, can modulate the expression of hormone receptors and disrupt the neuroendocrine stress axis later in life, Solomon-Lane has found. Other cichlid species have revealed neural mechanisms for sex differences in aggression, resilience and susceptibility to social defeat, and the determination of social hierarchies.

“If you want to understand how powerful the social environment is, you need an animal that responds to it in these nuanced and complex ways, and this fish can totally do that,” she says.