Transplanted eyes located far outside the head in a vertebrate animal model can see even without a direct neural connection to the brain, researchers have shown for the first time. The connections were tested using fluorescence microscopy, an LED light setup and camera-based motion-tracking technology. Biologists at Tufts University School of Arts and Sciences used a frog model to shed new light on one of the major questions in regenerative medicine, bioengineering and sensory augmentation research: how the brain and body adapt to major organizational changes. “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,” said Dr. Douglas J. Blackiston, first author of the paper, published in the Journal of Experimental Biology (doi: 10.1242/jeb.084921). Blackiston is a postdoctoral associate in the laboratory of co-author Dr. Michael Levin, professor of biology and director of the Center for Regenerative and Developmental Biology at Tufts University. 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 normal eyes can see using a functioning ectopic eye located in its tail. The dark area in the midsection is the stomach. Courtesy of D. Blackiston and M. Levin. The results eventually could lead to restoration of sensory function when parts of the body are damaged or missing, Levin said. Ultimately, he added, “we may not need to make specific connections to the brain when treating sensory disorders such as blindness.” In the experiment, the team surgically removed donor embryo eye primordia, marked them with fluorescent proteins, and grafted them into the posterior region of recipient embryos to induce the growth of ectopic eyes. The recipients’ natural eyes were removed, leaving only the ectopic eyes. Fluorescence microscopy showed various innervation patterns, but none of the animals developed nerves that connected the ectopic eyes to the brain or cranial region. To determine whether 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 allowed the scientists to monitor and record the tadpoles’ motion and speed. The team made exciting discoveries: Just over 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. This response was not demonstrated by eyeless tadpoles or tadpoles that did not receive any electrical shock. “This has never been shown before,” Levin said. “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.” The findings suggest 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. The work has many implications, Levin told BioPhotonics. “First, for regenerative medicine, it means that replacement organs may only need to be connected to the spinal cord, not have to be directly wired into the brain. “Second, for basic neuroscience, it establishes a new model for understanding neuroplasticity of the brain:body interface – the brain may be able to read the anatomical arrangement of the body plan and know where certain organs are. This is important for understanding evolution: It means that when a mutation changes the body plan in some beneficial way, the animal’s cognitive programs don’t suddenly become useless – the brain is plastic enough to map behavioral programs onto many different types of body plan; it’s not hard-coded. “Third, for human augmentation technology, our work provides a paradigm for connecting new sensors and effectors to a normal body. “Fourth, for robotics and synthetic bioengineering … we will be able to take lessons learned about how the brain operates a changing body to build flexible, robust, fault-tolerant robotic agents and communication/control networks.” The researchers’ next steps, Levin said in the interview, will be to determine how the ectopic eye’s information gets to the brain and how it is processed; to control innervation from the ectopic eye to force connections to the spinal cord using bioelectric technology they developed; to do the same in adult animals to create a vision repair model for adults; to find out how the brain identifies the information as image data, originating from a vision organ; and to “extend the paradigm of brains taking anatomical surveys of the body to other aspects of development and regeneration to study how the nervous system is used to process anatomical data and control growth.”