For decades the medical establishment treated the adult brain as fixed hardware. This episode traces the evidence that it is not, starting with Italian anatomist Michele Vincenzo Malacarne, who in 1793 trained one animal of a littermate pair for years and found its cerebellum substantially larger. Santiago Ramón y Cajal coined the term neuronal plasticity in the early 1900s over objections from peers such as Walter Spielmeyer. Eleanor Maguire’s MRI scans of London taxi drivers, who memorize the city for the exam known as the Knowledge, found larger posterior hippocampi that tracked their years on the job.

The episode separates structural plasticity, such as new dendritic spines and neurogenesis, from functional plasticity. David Hubel and Torsten Wiesel sutured one eye of kittens shut and saw the visual cortex rewire to the open eye, Michael Merzenich watched neighboring finger maps annex the territory of a severed nerve in monkeys, and Paul Bach-y-Rita’s vibrating chair let blind people perceive images through their backs. It then turns to maladaptive plasticity in addiction, phantom limb pain and chronic pain, and to treatments from Lorimer Moseley and Peter Brugger’s imagined movement exercises to the rapid antidepressant effects reported for ketamine.

• The empiricist versus nativist debate and the idea of constrained plasticity
• How repeated drug use reshapes the nucleus accumbens, likened to a sled carving an icy rut
• Phantom limb sensations in 60 to 80 percent of amputees as neighboring maps invade the hand region
• Chronic pain linked to reduced gray matter in the prefrontal cortex
• A 2009 study of brain changes after 15 months of musical training, and nicotine’s effect on acetylcholine receptors