Eyes ‘see’ without a brain

How can tadpoles see without eyes wired directly to the brain? The answer could lead to new inventions for the blind.
March 4, 2013

Researchers at Tufts University have shown that transplanted eyes located far outside the head in a vertebrate animal model can confer vision without a direct neural connection to the brain. In this image, a “blind” tadpole without its native (normal) eyes is able to see using functioning ectopic eye located in tail. Dark area in midsection is the stomach. (Credit: D. Blackiston and M. Levin/Tufts University)

Transplanted eyes located far outside the head in  tadpoles can give them vision without a direct neural connection to the brain, biologists at Tufts University have found.

The research sheds new light (literally) on one of the major questions in regenerative medicine, bioengineering, and sensory augmentation research.

“Our research reveals the brain’s remarkable ability, or plasticity, to process visual data coming from misplaced eyes, even when they are located far from the head,” says Douglas J. Blackiston, Ph.D.

Blackiston is a post-doctoral associate in the laboratory of co-author Michael Levin, Ph.D., professor of biology and director of the Center for Regenerative and Developmental Biology at Tufts University.

The research shows that we may not need to make specific connections to the brain when treating sensory disorders such as blindness, Levin notes.

The team surgically removed the eyes of several tadpoles, marked them with fluorescent proteins, and grafted them into the posterior region of recipient embryos. This induced the growth of ectopic eyes (located away from the normal position). The recipients’ natural eyes were removed, leaving only the ectopic eyes.

Fluorescence microscopy revealed various innervation (nerve-generating) patterns that connected to the spinal cord, but none of the animals developed nerves that connected the ectopic eyes to the brain or cranial region.

To determine if the ectopic eyes conveyed visual information, the team developed a computer-controlled visual training system in which quadrants of water were illuminated by either red or blue LED lights. The system could administer a mild electric shock to tadpoles swimming in a particular quadrant. A motion tracking system outfitted with a camera and a computer program allowed the scientists to monitor and record the tadpoles’ motion and speed.

How can tadpoles see when eyes are not wired directly to the brain?

The team made some exciting discoveries: More than 19 percent of the animals with optic nerves that connected to the spine demonstrated learned responses to the lights. They swam away from the red light while the blue light stimulated natural movement.

Their response to the lights elicited during the experiments was no different from that of a control group of tadpoles with natural eyes intact. Furthermore, this response was not demonstrated by eyeless tadpoles or tadpoles that did not receive any electrical shock.

“This has never been shown before,” says Levin. “No one would have guessed that eyes on the flank of a tadpole could see, especially when wired only to the spinal cord and not the brain.”

‘Remarkable plasticity’ discovery could lead to Implications

The findings suggest a remarkable plasticity in the brain’s ability to incorporate signals from various body regions into behavioral programs that had evolved with a specific and different body plan.

“Ectopic eyes performed visual function,” says Blackiston. “The brain recognized visual data from eyes that impinged on the spinal cord. We still need to determine if this plasticity in vertebrate brains extends to different ectopic organs or organs appropriate in different species.”

“CNS plasticity will allow ectopic organs to function even through novel pathways, with sensory information being transferred through the co-option of auditory, visual, mechanosensory, nociception, thermoreception, or other existing neural systems,” the authors suggest in the paper.

“In addition, a number of devices can transduce visual data into sound (echolocation) [as shown in the surprising skills of some blind people such as Micheal Hingson to use clicking noises to navigate], electrotactile stimulation of the skin, or electrical stimulation of the tongue. In the case of blind individuals, extended use of these devices stimulates neuronal activity within the visual cortex of the patient even though these ‘visual’ data are delivered through decidedly non-visual pathways

“Moreover, understanding the robust mechanisms of such plasticity will have numerous applications for the development of fault-tolerant and resilient communications and control networks in many areas
of engineering. Indeed a promising recent direction is the development of cybernetic devices that are not pre-programmed with a description of their own structure but must discover their morphology dynamically.”

One of the most fascinating areas for future investigation, according to Blackiston and Levin, is the question of exactly how the brain recognizes that the electrical signals coming from tissue near the gut is to be interpreted as visual data.

In computer engineering, notes Levin, who majored in computer science and biology as a Tufts undergraduate, this problem is usually solved by a “header”—a piece of metadata attached to a packet of information that indicates its source and type. Whether electric signals from eyes impinging on the spinal cord carry such an identifier of their origin remains a hypothesis to be tested.

Another possibility might be that the plasticity of the tadpole brain allows it to respond to stimuli from an ectopic organ by recognizing characteristic patterns that are uniquely native to visual signals.For example, a Brown University study (open access) found that, during early tadpole development, spatial tuning is sensitive to developmental changes in the temporal pattern of recurrent activity.

The research was supported by grants from the National Institute of Mental Health of the National Institutes of Health and the National Eye Institute, also of the NIH. Additional funders were the Leila Y. Mathers Charitable Foundation and the U.S. Army Medical Research and Materiel Command.