Year-round sailor: Hear Bear talk about his passion for sailing. Watch more video of Mark Bear on sailgroove.org

He should know. On the water, in a boat inaptly named “Fat Bastard,” Bear has won the U.S. Masters National Championship and the New England Championship. In the lab, he’s challenged reigning dogmas in neuroscience.

Over a quarter century, Bear has tacked toward elusive problems in his field. His main obsession has been brain plasticity: the process by which neurons change in response to experience. Early on, he explored neural connections in the hippocampus, which plays a key role in long-term memory and spatial navigation. Controversially, he used these findings as a model for a very different part of the brain, the visual cortex.

More recently, Bear has applied his discoveries in brain plasticity to understanding fragile X syndrome, an inherited form of mental impairment. He has described surprising mechanisms underlying fragile X and has shepherded a promising treatment through phase 2 clinical trials testing for efficacy in patients. The course he has charted may yield the first neurobehavioral targeted pharmaceutical treatment that grew from the bottom up: from gene discovery to an understanding of pathophysiology to a targeted drug.

Early Inspiration

On November 22, 1963, the day President John F. Kennedy was assassinated, six-year-old Mark Bear was glued to the television. What transfixed him, even then, were the early conjectures from newscasters about what Kennedy’s life would be like if he survived the gunshots to his head and neck. “I remember being astounded: so much resides in the brain,” Bear says. The next Christmas, he asked his parents for a human brain modeling kit.

Now 53, Bear has the look of an ageless East Coast postdoc: neat but decidedly casual—khakis, crew neck sweater, hiking boots. He is tall and fine-featured, with a slightly receding hairline and an early morning hint of a five-o’clock shadow. His eyes often have an abstracted and amused expression, as if he’s formulating a joke.

Across the street from where he works on the MIT campus, dominating the view through his lab’s plate glass windows, is Frank Gehry’s Stata Center: big and boxy, with defiantly jangled angles. It’s an odd panorama. In his unassuming office, Bear—sometimes slouched, sometimes leaning forward to explain a fine point of science—is soft-spoken but plainly passionate about the mysteries of the brain.

In the decades since JFK’s death, neuroscience came of age, and Bear caught the wave. Researchers learned that the brain’s adaptive plasticity extends into adulthood. And this plasticity is centered in the synapse—the junction across which a nerve impulse passes from one neuron to another. At the synapses, axons—the long, slender projections of nerve cells that conduct electrical impulses to target cells—connect to dendrites, the short-branched extensions of nerve cells that ferry impulses toward the cell body. The terminus of the sending cell contains neurotransmitters, chemicals that diffuse across the gap and activate sites on the target cell, called receptors. Synaptic plasticity is the ability of the connection between two neurons to change in strength.

Figuring out the basis of this plasticity has been Bear’s mission from the start. To convey how he has gone about that quest, he switches metaphors from the sea to the casino. “Imagine nature as a deck of cards,” he says. “The first experiment you do should not be one where you peel off a card from the top. It should be the deck-splitting experiment. The most incisive experiment. The experiment that most narrows the range of possibilities and will define your subsequent course.”

Bear launched his career as a doctoral student at Brown University, followed by a postdoctoral fellowship with Wolf Singer at the Max Planck Institute for Brain Research, in Frankfurt, and a return to Brown with his own lab. His research spun off from a well-studied phenomenon known as long-term potentiation, or LTP. When a rapid train of strong nerve impulses hurtles down an axon, the synapses that connect the axon to the dendrites of other neurons are strengthened, or “potentiated.” LTP is one of the cellular processes underlying learning and memory.

What piqued Bear’s interest was the opposite process: synaptic weakening, a phenomenon known as long-term depression, or LTD. He was inspired by classic experiments performed in the early 1960s by Harvard University’s David Hubel and Torsten Wiesel that won them the 1981 Nobel Prize in Physiology or Medicine. They temporarily sealed one eye in infant kittens. When the eye was reopened weeks later, neurons in each animal’s visual cortex no longer responded to stimulation, while brain cells compensated by responding more strongly to inputs from the open eye. In effect, the kittens’ brains had rewired themselves under visual deprivation—enough to cause permanent blindness.

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