Aquaria at the California Institute of Technology in Pasadena bustle with tiny translucent jellyfish, adrift like dust motes in a sunbeam, rhythmically pulsing with long tentacles in tow. They’re beautiful—they may also be an important tool for neurobiologists.
According to a recent study in Cell, the Mediterranean jellyfish Clytia hemisphaerica is a viable model organism for neuroscience research. Caltech researchers created several genetically modified populations of the species and demonstrated that simple genetic changes had behavioral consequences useful for studying the jellyfish nervous system.
“Objective one was to establish this as a model to do neuroscience,” says neurobiologist and lead author Brandon Weissbourd of the recent study. The jellies’ small size and transparent bodies make these cnidarians particularly attractive for neuroscience research, according to Weissbourd, a Caltech postdoc. “We can put a whole jellyfish under a microscope and see the whole nervous system at once,” he says. Jellyfish are also evolutionarily distant from established neuroscience model organisms such as worms, flies, fish, and mice. Having an outgroup could be useful for future comparative studies of the major models of the nervous system, notes Weissbourd.
Clytia hemisphaerica is already a model in developmental biology. Collaborators of the Caltech group in the South of France have used it to study egg development, embryology, and evolution for more than a decade. To repurpose the jelly for neuroscience studies, Weissbourd’s team first needed to decide on the genetic modifications necessary to image and study the nervous system. They knew that neurons in this species are arranged in one or, likely at least two concentric rings around the edge of the bell, with a net-like web of neurons on the underside of the body and the tentacles. Research in the 1980s showed that a subset on the jelly’s underside produce RFamide (RFa) peptides, which in other species can indicate a distinct population of neurons with related functions.
So to make a genetically modified jelly, Weissbourd and collaborators inserted a gene that killed the RFa-producing neurons in response to a drug in the water. Jellies swimming with the drug lost their ability to pass food from their tentacles to their mouths. (Without the neurons controlling that behavior, they couldn’t contract the muscle that flexes the rim of the body in toward the mouth.)
Weissbourd’s next question: How is the nervous system organized to generate this behavior? He made a new line of genetically modified C. hemisphaerica, this time inserting a different gene to express the calcium indicator GCaMP. When neurons fire, calcium floods the cell, and the GCaMP indicator, a combination of green fluorescent protein and other peptides, glows green, enabling researchers to watch the neurons activate in real time. Imaging jellyfish feeding behavior in the GCaMP population revealed wedges of neurons arranged like illuminated pie slices around the circular underside of the body. That’s “a surprising degree of intrinsic organization,” Weissbourd says.
He’d expected much more random nervous system activity in which any neuron might fire with any of its neighbors. “But what we actually found was something more intermediate,” Weissbourd explains. Highly connected subgroups of neurons were consistently more likely to fire together, but nonetheless generated a huge diversity of possible wedge shaped neuronal populations.
Jellyfish are especially well poised to help answer some of the biggest questions in neuroscience today, including what the earliest nervous systems looked like, says evolutionary developmental biologist Thomas Bosch, at Kiel University, in Germany. Bosch, who was not involved in this recent study, calls the work “beautiful,” and notes that it’s “remarkable” how complex jellyfish behaviors can be, despite their lacking a centralized brain. These delicate creatures may help neuroscientists understand the minimum complexity that a nervous system needs to perform complex behaviors, he says.
“Cnidarians, such as jellyfishes, corals, sea anemones, and hydrozoans, are extant representatives of the first animals with nervous systems,” notes neurobiologist Rafael Yuste at Columbia University in New York. “In a way, by studying cnidarians, one can uncover evolution’s first baby steps in the design of brains.”
This first paper is just the start, Weissbourd says. RFa-producing neurons are also at work in the tentacles and around the mouth, hinting they may coordinate feeding behavior across all these body parts, he says. So far, it seems likely that the neurons initiate muscle contraction on the jelly’s underside, but as to what else they might do in other body areas, he says, “at this point, we don’t know.”
Future research could flesh out the neuroscience of C. hemisphaerica feeding, and of other behaviors such as swimming and defense. In general, neuroscientists are finding organisms to be more complex and more organized than expected, Weissbourd notes. These latest findings are no exception. “Jellyfish are thought to be sort of simple,” he says. “But it turns out they have more complicated mental lives than we maybe imagined.”
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