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Model organisms: new kids on the block

 

 

Heidelberg, 2 August 2017 – Neuroscientists are looking beyond worms, flies and mice to study the evolution and function of the nervous system. Katrin Weigmann talked to organisers and speakers of the EMBO | EMBL Symposium “Neural Circuits in the Past, Present and Future” about their experience of working with different model organisms.

 

There are more than 1.5 million known species on earth, but researchers have focused mainly on about ten so-called model organisms such as Drosophila, C. elegans or Mus musculus. This limited selection has a major drawback: “Instead of studying general principles you may end up looking at something that is very specific to one species,” says EMBO Member Detlev Arendt of the European Molecular Biology Laboratory. According to Arendt, it is time to open up to diversity. “For a long time, the good excuse to ignore about 99.9999% of species was that it was technically almost impossible to study them. But this is now changing.”

 

Neuroscientists play a lead role in this change thanks to technological advances. “Neural circuits can be studied in animals where some molecular technologies are still falling short,” explains Arendt. Comparative approaches are becoming a strong theme in neurobiology, teaching researchers a lot about the principles of nervous system function.

 

The EMBO | EMBL Symposium on Neural Circuits “opened peoples’ eyes to the diversity of what it means to be a neurobiologist,” says Richard Benton. The researcher at the University of Lausanne co-organized the symposium that took place in Heidelberg in May 2017 with Arendt and Leslie Vosshall from the Rockefeller University in New York City. Neuroscientists are now working on sea slugs, annelids, nematodes, mosquitoes, dragonflies, salamanders, lizards, mice, and more, choosing specific organisms depending on the questions they are looking to answer.

 

Of sponges and worms

 

Arendt, for example, investigates the evolutionary emergence of nervous systems using simple organisms like sponges, sea anemones and annelids. In the first multicellular organisms, each cell performed various functions. Muscles and neurons then evolved from these cells through division of labor. Many components of the synapse, however, predate the origin of neurons. Synapses evolved through the integration of modules with independent functions, such as exocytosis, reception and cell adhesion. Finally, neurons diversified, but many cell types once thought to be specific to vertebrates are also present in annelids, indicating an early evolutionary origin. “The complex structure of the nervous system can only be understood in the light of evolution,” says Arendt.

 

Branching out with close relatives

 

Branching out from the more traditional model organisms also enables researchers to study the genetics underlying the evolution of particular neural circuits. Whereas Drosophila melanogaster is a generalist that feeds on almost any fermenting fruit, its relative Drosophila sechellia lives on one specific fruit found on the Seychelles. Benton studies how the olfactory system adapted to this highly specialized lifestyle. At the level of olfactory receptors, a single amino acid change was sufficient to alter the tuning of one receptor towards an odor of its preferred fruit. At the level of the circuit, the number of neurons that express this receptor has increased. “Using these closely related species we can study the genetic basis of functional and anatomical differences between neural circuits and draw conclusions about how they evolved,” explains Benton.

 

EMBO Member Ralf Sommer at the Max Planck Institute for Developmental Biology in Tübingen, Germany, studies the role of phenotypic plasticity in evolution using the nematode Pristionchus pacificus. Depending on the environment and food resources, P. pacificus can develop one of two alternative mouth forms which coincide with distinct feeding behaviours, one of which is a predatory form. Sommer and his colleagues identified key genetic switches that are regulated by epigenetic factors and control mouth-form plasticity. This paved the way to investigating the impact of environment and epigenetics on evolution. “According to our data, genes that regulate phenotypic plasticity are not well conserved in evolution and there are theoretical studies that suggest that genes are just followers rather than leaders. Our data are consistent with this notion,” says Sommer. In addition, he and colleagues have investigated how homologous neurons changed their connectivity to generate the new feeding behaviour in one of the mouth forms. This has become a widely-cited example of how neural rewiring alters behaviour.

 

Comparing circuits and behaviour

 

With about 10,000 neurons, the brains of sea slugs are considerably larger than those of C. elegans or P. pacificus. Nonetheless, they are small enough to make it possible to identify homologous neurons and compare circuits and behaviours between related species. Paul Katz at Georgia State University investigates central pattern generators – neural networks that cause rhythmic motor patterns such as in walking or swimming. He found that similar swimming behaviours in different sea slug species may rely on different underlying neural circuits.

 

In one example, Katz has identified what he calls a “circuit drift” – a rewiring of neurons without changing behaviour. Melibe and Dendronotus both swim with left–right flexions, as do all animals within their clade. They also use homologous neurons to generate this swimming pattern. However, the connectivity between the neurons and their firing pattern differs. “The circuit can change a little without destroying the behaviour. This example shows that there are many ways of creating a certain function,” Katz explains.

 

He also studies cases where similar modes of locomotion have evolved independently. “When you find species that came up with the same solution to a problem through completely different lineages, this tells you a lot about the underlying neural principles,” he adds. For example, most central pattern generators rely on inhibitory rather than excitatory connections to maintain rhythmicity. It just seems to be the best way of doing it.

 

Richard Benton discovered another example of convergent evolution when he found that insect odorant receptors define a novel class of genes, unrelated to odorant receptors in vertebrates. “This suggests that olfaction has evolved independently in invertebrates and vertebrates,” says Benton. There are, nonetheless, many parallels in terms of the anatomical and molecular logic of their olfactory systems. In both vertebrates and invertebrates, almost all olfactory sensory neurons express only one type of olfactory receptor. In addition, neurons expressing the same receptor converge onto discrete glomeruli in the primary olfactory center of the brain. “Different lineages evolved the same kind of neural processing solution to the same sensory challenge. If you were designing it as an engineer you may well come up with the same circuit organisation,” says Benton.

 

Mapping out the future

 

“Neuroscience right now is driven a lot by technology that allows us to ask new questions in new models,” adds Benton. Recent developments in connectomics illustrate this point. Researchers are determining the connectomes of both traditional and less traditional organisms. The connectome of the annelid Platynereis was only recently determined by Gáspár Jékely at the Max Planck Institute for Developmental Biology. Arendt and his group now take this achievement one step further. They combine the connectome with a complete map of the molecular fingerprint of neuronal cell types that is based on their evolutionary analysis – a useful tool when it comes to comparing homologous cells and their connectivity in different species. According to Benton, “we are starting to see the commonalities of diverse animals in how they use similar types of molecules, neurons and circuits in the brain.”