In the 1940s, the Nobel prize–winning neurobiologist Roger Sperry performed some of the most important brain surgeries in the history of science. His patients were newts.
Sperry started by gently prying out newts’ eyes with a jeweler’s forceps. He rotated them 180 degrees and then pressed them back into their sockets. The newts had two days to recover before Sperry started the second half of the procedure. He sliced into the roof of each newt’s mouth and made a slit in the sheath surrounding the optic nerve, which relays signals from the eyes to the brain. He drew out the nerve, cut it in two, and tucked the two ragged ends back into their sheath.
If Sperry had performed this gruesome surgery on a person, his patient would have been left permanently blind. But newts have a remarkable capacity to regrow nerves. A month later Sperry’s subjects could see again.
Their vision, he wrote, “was not a blurred confusion.” When he dangled a lure in front of one of the newts, the creature responded with a quick lunge. It was a peculiar sort of lunge, though: The animal looked up when the lure was held below and down when it was dangled overhead. Sperry had turned the newt’s world upside down.
The experiment revealed that nerve cells, or neurons, possess a tremendous capacity for wiring themselves. Neurons grow branches known as dendrites for receiving signals, and sprout long outgrowths called axons to relay the signals to other neurons. Axons in particular can travel spectacular distances to reach astonishingly precise targets. They can snake through the brain’s dense thicket, pushing past billions of other neurons, in order to form tight connections, or synapses, with just the right partners.
The neurons in the eyes of Sperry’s newts regrew their axons, eventually linking up to neurons in the vision-processing region of the brain. Evidently the axons from the eyes were able to find the same parts of the brain that they had been linked to before the surgery. The only difference was that the post-operation eyes delivered inverted images, because the eyes had been rotated but the neuronal connections that they made unfolded as normal.
Six decades of research have made clear that Sperry’s newts were not unusual. All animals have nervous systems that wire themselves together with great precision. In humans this process starts in the womb, when the first neurons begin to develop. Their axons can go great distances, the longest ones extending all the way from the toes to the base of the spine. Even after our brains have developed, some neurons continue to wire themselves: Nerves heal from small injuries, and axons make new connections as we develop new skills.
When neurons fail to wire correctly, our bodies and brains go awry in many ways. About one in a thousand babies is born with a disorder called Duane syndrome, in which the nerves controlling the eye muscles send some of their axons to the wrong destinations. Axons that are supposed to grow into the muscle on the eye’s inner edge may end up on the outer edge instead. When people with this syndrome try to turn an eye inward, they send a message to the muscle on the inside edge to contract. But the same message also goes to the muscle on the outside edge. Both muscles pull at the same time, yanking the whole eye back into its socket.
Inside the brain, the results of bad wiring can be even more devastating. Normally, 200 million axons cross from each hemisphere of the brain to the opposite side. In a disorder called agenesis of the corpus callosum (agenesis meaning “lack of development”), many axons cannot find their way out of their own hemisphere. Instead, their axons curl together into large bundles. People with this form of agenesis have trouble moving information from one hemisphere to the other. They end up with a lot of autism-like symptoms: They have a hard time understanding figurative language and inferring what other people are thinking, for example.
To better treat wiring disorders, scientists are trying to understand how neurons form circuits. But almost 70 years after Sperry’s newt surgery, the wiring question remains one of the deepest mysteries in neuroscience. One reason why is that the wiring problem is actually a series of problems, each of which our neurons may solve in several ways.