Blind tadpoles learn visually with eye grafted on tail

The strategy uses a drug already approved in humans and could provide a road map for promoting the supply of nerves to new organs in regenerative medicine.

In a new study, blind tadpoles were able to process visual information from eyes that were grafted onto their tails after being treated with a neurotransmitter drug. Researchers used a neurotransmitter drug called Zolmitriptan, which is already approved for other uses in humans, to enhance integration and functionality of the grafted eye.

We spoke to Michael Levin from Tuft University’s Allen Discovery Center about the study and what it means for regenerative medicine.

ResearchGate:  Why put an eyeball on a tadpole’s tail?

Michael Levin: We are interested in understanding how information is spread across tissues, how the brain deals with altered body architectures, and how implanted structures can be optimized. We developed this model as an ideal platform to study these questions. The fact that tadpoles can use ectopic eyes, eyes placed where they don’t usually form, for image-forming vision shows that the brain has remarkable plasticity to deal with altered body structures, and that this technique can improve the functional performance of transplanted organs.

Blind tadpoles with eyes grafted onto their tails were able to process visual information after being treated with a small molecule neurotransmitter drug. Credit: Allen Discovery Center at Tufts University.

RG: Can you tell more about your findings?

Levin: We basically found that the supply of nerves emerging from transplanted eyes into the host can be drastically increased by a drug already in use in human patients for other purposes. We found that this increases the efficiency of integration of the eyes placed on the tails of tadpoles. The tadpoles could  see not only colors, but also shapes and movement.  These eyes don't connect directly to the brain, but rather to the spinal cord.

RG: How could you tell whether the tadpoles were seeing?

Levin: We used several tests, including a special machine we designed for training tadpoles based on color cues. We also watch the tadpoles react when placed on top of an LCD monitor showing moving patterns of black shapes, which tadpoles can perceive as predators or siblings.

RG: Why did you use tadpoles?

Levin: Tadpoles are a uniquely perfect system for this work because they are amenable to genetic manipulation, can be treated with neurotransmitter drugs, have both learning ability and social behaviors, and can be surgically manipulated. They are a popular system to study, because they are a complex vertebrate with many of the pathways relevant to human medicine.

RG: What are some potential applications this could have in humans?

Levin: Some applications could be to improve nerve supply and functional integration of transplanted human organs or implanted bioengineered constructs, and also exploit the fact that such organs don't have to be connected to the brain; connection to the spinal cord may be sufficient. The big picture is that by understanding how the brain and body communicate, a whole new class of sensory augmentation, body structure modification, and regenerative therapies become possible. This study is also a proof-of-principle of repurposing the existing toolkit of drugs for novel applications in the control of developmental bioelectricity.

Featured image courtesy of m.shattock.