Synapses—the junctions between nerve cells—are the highways for messages sent and received by every cell in the brain. How do synapses change over time, and how do these changes affect the brain?
These are questions that Mark Bear has been answering. Bear first became interested in the human brain on a day etched into the memories of many: November 22, 1963. After President John F. Kennedy was shot, the 6-year-old Bear listened to radio announcers discuss whether the president, if he survived, would be able to speak again. Bear was fascinated by the idea that the power of speech could be encapsulated in part of the brain. At least one of his subsequent Christmas lists included a request for a modeling kit of the human brain. Santa never came through, but that didn’t dampen Bear’s interest.
In college, Bear discovered a new neural connection in the brain. Surprised that there were still such basic discoveries to be made, he went on to graduate school in neuroscience. There, he became intrigued by an experiment done in the 1960s, in which a newborn kitten’s eye was sewn shut for several weeks. When the stitches were removed, the brain had stopped responding to the eye. This result models a human condition called deprivation amblyopia—blindness that results not from dysfunction of the eye, but from a failure of the brain to respond to visual input.
Bear’s research in this area led to the discovery of a phenomenon called long-term depression, or LTD. Studies of LTD have revealed many mechanisms that cause synapses to weaken, and his current research is aimed at understanding how these contribute to deprivation amblyopia.
Bear’s research not only had implications for vision problems, but also for an inherited condition called fragile X syndrome, the most common cause of inherited mental retardation. Studies of LTD led to the hypothesis that new proteins are synthesized at synapses in response to activating a neurotransmitter receptor called an mGluR. In a collaboration with Stephen Warren at Emory University, Bear and his colleagues found that mGluR-stimulated protein synthesis and LTD are excessive in fragile X. Subsequently, researchers in Bear’s lab discovered that reducing the activity of mGluRs can correct multiple symptoms of fragile X in mice. Studies with drugs that block mGluRs are now under way in humans with fragile X. “It is incredibly gratifying to see that studies of the basic mechanisms of LTD have led to insights that could lead to correction of a devastating human disorder,” says Bear.
In 2006, Bear provided the first evidence that learning leads to the strengthening of nerve signals, a process called long-term potentiation (LTP). Bear’s lab monitored changes in the brains of rodents that learned to avoid a fearful situation in a maze. The discovery was cited by Science magazine as a runner-up for Breakthrough of the Year.
Bear’s studies also have found that LTP in a nerve cell is partly regulated by its recent history of activity. He has dubbed this phenomenon “metaplasticity” and continues to study its mechanisms. Bear believes that tapping the mechanisms of metaplasticity will lead to better strategies to promote recovery of function after brain damage.
Bear lives in Boston, Massachusetts. He is an avid sailor, racing 14-foot, one-person boats called Lasers. Bear has won the U.S. Masters National Championship as well as the New England Championship. In 2002, he was second in the Masters World Championship.