A beautiful marine creature with a jelly-like body surrounded by iridescent combs. The most likely candidate for the earliest branched-off animal lineage. And now, an impossible nervous system. Comb jellies may be too small to even cause ripples in the water as they swim, but their unique features are creating shockwaves in the scientific community.
A recent study, published in Science, looked closely at the nerve-net neurons of comb jellies and found that instead of being connected by synapses – junctions between neurons in all other animals, including humans – they are continuously connected by a single plasma membrane.
Comb jellies, or ctenophores, belong to phylum ctenophora, and are one of the oldest animal lineages with a defined nervous system. They are quite hard to culture in the lab, however, yet Pawel Burkhardt managed to do just the thing in his lab at the Michael Sars Centre at the University of Bergen, Norway.
“This was something that all came together, step by step. We were able to basically disentangle the nervous system,” Dr. Burkhardt told The Hindu.
He had collaborated with Maike Kittelmann of the Oxford Brookes University in the U.K. previously for a study, published in Current Biology in 2021. In this study, they examined a single neuron in the nerve-net using high resolution electron microscopy. They found that the neurites – the branches from the neuron that form synapses – were all interconnected by a single plasma membrane, a feature not seen in the neurons of other animals.
For the new study, they wanted to see how a single nerve-net neuron could make connections with other nerve-net neurons. When they observed the microscopy images of the different nerve-net neurons together, they were taken completely by surprise.
“We expected synapses,” said Dr. Kittelmann. “We went in there to find the synapses between the nerve-net neurons, but we just couldn’t find them, because they aren’t there.”
The researchers conducted their experiments with ctenophores in the predatory cydippid stage, an earlier stage in the ctenophore life cycle when it is capable of reproducing. They used high-pressure freezing and fixing and electron microscopy to build a 3D view of all the neurons within the nervous system of ctenophores.
When they examined how some neurons connected to others in the cydippid, they found synaptic connections. But the five neurons within the nerve-net seemed to all be interconnected via a syncytial network, i.e. without any synapses.
In the 1950s, the use of electron microscopy helped confirm neurobiologist Ramón y Cajal’s hypothesis that neurons were separate cells connected via synapses. It put to rest a long debate about whether neuronal networks in most animals formed a continuous syncytium or were made up of discrete cells.
In an ironic twist, the new study again demonstrated the usefulness of more advanced microscopy techniques to show that in ctenophores, at least in the nerve-net neurons, it’s the opposite: it is a syncytium.
Ctenophores have been at the centre of a heated debate over the identity of the first animal. Whole-genome sequencing studies of ctenophores, published in 2013 in Science and 2014 in Nature, added evidence to the theory that ctenophores were the earliest branch of the animal kingdom and form a sister group to all other animals.
But even if ctenophores constitute the oldest animal lineage, biologists are still unclear as to how their nervous system evolved. Based on his findings in the 2014 Nature paper, Leonid Moroz of the University of Florida proposed a controversial theory. He said that the nervous system could have evolved twice, once in ctenophores and once in other animals.
His paper and another study that followed pointed to ctenophores having a unique nervous system. The ctenophore genome didn’t show classical neurotransmitter pathways present in other animals nor did ctenophore neurons express the common genes associated with other animal neurons.
“Our paper is not proof for or against the independent evolution of the ctenophore nervous system,” Dr. Burkhardt said. “However, given that ctenophores are very early branching animals and that the nerve-net architecture of ctenophores is unique, it is possible that the nerve-net evolved independently.”
According to him, the fact that ctenophores use cilia, and not muscles, to move could also be a reason why they would possibly evolve a different signal conduction system.
“It is a fantastic finding that nerve-nets can also be syncytial,” said Detlev Arendt, a researcher at the European Molecular Biology Laboratory who studies the evolution of nervous systems. “We have to understand how such a nerve-net operates as compared to other nerve-nets that are connected with synapses or gap junctions.”
Dr. Burkhardt and Dr. Kittelmann are keen to study the nerve-net neurons as the ctenophores develop, to see if adult ctenophores retain the syncytial nerve-net or if they develop synapses.
For Dr. Moroz, the results are more evidence for the ctenophore nervous system’s unique nature and signs that it could have evolved independently. More importantly, he stressed the importance of such studies in a broader context – of how unique animal systems like the ctenophore can help us understand how the nervous system has evolved to work so perfectly, even in humans.
“Nature has offered to us alternate unique examples of how to get the same outcome in different ways,” Dr. Moroz said. “The shortcut to understand the fundamentals of neuronal function and treat a variety of disorders will come from comparative analyses.”
There is a lot more to do to further understand the functional and evolutionary significance of the syncytial nerve-net neurons in ctenophores. This study provides an important anchor for such research into nervous system evolution in animals, research which Dr. Moroz firmly believes is essential to understand the principles of brain function.
“To understand our brain, we have to understand alternate strategies,” he said. “To understand our brain, we have to study small creatures in the sea.”
Rohini Subrahmanyam is a freelance journalist.
