Why did scientists generate electrodes in zebrafish brains?

Why did scientists generate electrodes in zebrafish brains?

The injectable gel being tested on a microfabricated circuitShare on Pinterest
Pictured, the injectable gel being tested on a microfabricated circuit. Image credit: Thor Balkhed.
  • Studying the brain is difficult, and often involves invasive techniques, such as using a probe, to gain information about electrical signaling.
  • This means our understanding of exactly how brain signaling works is limited, which has implications for basic science and medical research.
  • A research team has discovered a way to inject an enzyme-containing gel into zebrafish brains, which triggers a reaction that causes it to turn into an electrode.
  • This can be used to measure electrical cell signaling in the brain, which could have further clinical and research applications in the future.

Studying the brain is notoriously difficult. Sampling it in a living person is next to impossible, probing it is invasive, and getting drugs to cross the blood-brain barrier to observe how it behaves, challenging.

One of the most important breakthroughs in biology in the past decade has been harnessing the ability to influence stem cells, either embryonic or human stem cells, to form particular cell types.

Researchers have cultured these to form mini-organ models or organoids.

Organoids have proved particularly useful for studying the brain, and the different types of cells that the brain and nervous system are made from.

For example, one of the earliest uses of organoids was to develop a model of a person’s brain using induced pluripotent adult stem cells from their skin.

One area of current research focuses on seeing if models recreate the structures that develop naturally. So far, researchers have created brain organoids that demonstrate eye-like structures, and others that were able to integrate with rats’ brains, and even heal injured areas of tissue.

In addition to this area of study, there is also work being done to study brain cells in vitro, or in a Petri dish, using induced pluripotent stem cells, to gain greater insight into how brain cells or neurons work.

Last year, a debate was launched when scientists from University College London in the United Kingdom and the start-up Cortical Labs, announced they had developed DishBrain, which integrated brain cells onto computing devices using multiple electrodes.

They used this device to “teach” neurons how to play the computer game Pong, and published the results in Neuron.

This emerging area of research, known as “bioelectronics,” can also give us an insight into how brain cells work. Brain and nerve cells work by transmitting electrical activity and using these for cell signaling, as well as signaling using chemical cell signaling used by other cells.

By being able to merge electronics with nerve cells, we can measure cell signaling in a less invasive way than what is currently required when using a brain probe to measure electrical activity, for example.

Less invasive techniques may not only be more ethical but they might produce more reliable results, as there is less chance of interference from the invasive technique itself.

One of the biggest challenges facing those trying to merge electronics and living tissues is making the structure compatible: One is animal and one is mineral, after all.

Most of the recent advances in this area take place on silicone structures, or on specially designed films in a Petri dish, but these are difficult to merge with living tissues.

Recently, a group of scientists based in Sweden has created an injectable gel that undergoes polymerization — a kind of crosslinking — which allows it to act as an electrode and carry electrical signals.

The process was demonstrated in zebrafish brains and leeches, and the research findings outlined in a paper published in the journal Science.

In the paper, researchers describe how they created an “injectable cocktail gel” containing an enzyme that triggers a signaling cascade that leads to the polymerization, or linking, of other molecules in the “cocktail” in the presence of lactate, which occurs naturally in the body, and in the central nervous system.

The linking of the molecules that occurs allows them to conduct electrical signals, meaning that the gel forms an electrode when in contact with chemicals that naturally exist in the brain.

Researchers tested how resilient the electrode that had been formed was to harsh environments, and also tested its biocompatibility and found no negative effects on the zebrafish, said lead author Dr. Xenofon Strakosas, principal research engineer in the Laboratory of Organic Electronics at Linköping University, Norrköping, Sweden in an interview with Medical News Today.

The experiments were a proof of concept, he explained:

“Next week, we have collaborations with more advanced animal models like mice and rats and stuff. In the beginning, we optimized these processes in zebrafish and leeches to deduce animal modeling to prove that this can be biocompatible [and] will not interfere with the normal functional sort of the models.”

“For example, in the zebrafish, we didn’t see any side effects. So this was the proof of concept. And now we are moving towards different applications,” Dr. Strakosas noted.

The electrode formed in the brain by the gel could be attached to devices that record electrical signaling, shedding light on the ways that these cells signal with each other.

Though the gel has not been tested on heart tissue, it could have some applications in studying electrical signaling in the heart, Dr. Strakosas explained.

Dr. Brett Kagan, chief scientific officer of Cortical Labs, which was behind the DishBrain discovery reported last year, who was not involved in the current research, told MNT in an email:

“This is an exciting step forward in interfacing with living brain and other electrically active tissues for research purposes, with evidence for being able to investigate less accessible regions less invasive than is typically done.”

“While much more work is still required even for this to be commonly implemented in animal research, it is possible that it may even provide a basis for future developments that could one day lead to more complex applications of this approach even in humans,” Dr. Kagan added.