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Todd Sacktor's Search For The Memory Enzyme

Todd Sacktor's Search For The Memory Enzyme

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Published by Michael Humphrey
More than twenty years ago, Todd Sacktor, a neuroscientist at SUNY Downstate in Brooklyn, discovered the enzyme that may well be the engine that drives long-term memory. Starting in the fall of 2009, I began a series of interviews with Sacktor as well as over a dozen neuroscientists to try to understand both the molecule and the man who discovered it.
More than twenty years ago, Todd Sacktor, a neuroscientist at SUNY Downstate in Brooklyn, discovered the enzyme that may well be the engine that drives long-term memory. Starting in the fall of 2009, I began a series of interviews with Sacktor as well as over a dozen neuroscientists to try to understand both the molecule and the man who discovered it.

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Published by: Michael Humphrey on May 25, 2011
Copyright:Attribution Non-commercial


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By Michael Humphrey
a story about the day he chose science ashis field. The year would have been 1966. The memory is a snapshot: He is sittingon the floor of his grandmother’s Bronx high-rise apartment overlooking theHudson River. He is reading a newly purchased book called Understanding theBrain by the Nobel laureate John Eccles. It’s a happy day for the nine-year-old inwhat was sometimes a tumultuous childhood – the family drove from Baltimore tosee his beloved “granny,” for Thanksgiving, perhaps, though he can’t be sure of that detail. Sacktor devours Eccles’ illustrations, clear descriptions and grand tone– the book claims the human brain is “the most complexly organized matter in theuniverse.” He closes its pages with missionary zeal to take Eccles’ title seriously –he will understand the brain.In 1990, his first year at SUNY Downstate Medical Center in thegritty East Flatbush district of Brooklyn, Sacktor made what manybelieve was a major discovery to do just that. He discovered anenzyme in the brain called PKMzeta, which he suspected – and hassince demonstrated – keeps a long-term memory persisting in thebrain, even when the mind is not consciously engaging it. What that9-year-old child could not have known, what even Sacktor the adult did not realizeat first, was a basic truth about science – claiming a novel discovery places you
squarely in the professional desert. For the next 16 years, his peers largelyignored his work while he published in lesser journals and gave unheralded talks.Still, Sacktor single-mindedly pursued the purpose of the enzyme’s existence,certain he was onto a big discovery. Then five years ago a team of neuroscientists, led by Sacktor, ran a series of tests on rats’ memories that revolved around the enzyme. Their finding, named a“Top Ten Breakthrough of 2006” by
, was simple, fascinating anddisturbing – keep PKMzeta from doing its job for just a few hours and memoriesthat could have lasted a lifetime are forgotten forever without any damage to thebrain. Two months ago, a
report written by a team at the WeizmannInstitute showed that an “overexpression” of PKMzeta enhanced memory retentionof rats.Deep in the recesses of the Society for Neuroscience website is a snapshotof Sacktor from 2008. The society has just awarded him the Research Award forInnovation in Neuroscience, which comes with a $25,000 prize. In his black suitand black tie, Sacktor, a 52-year-old, smallish, wispy-haired man with sharpfeatures, peers down at the camera from the podium, his mouth smiling butclosed, his round face nearly expressionless. His eyes tell the story. They are notwide, thankful eyes of other neuroscientists pictured on the website from previousaward ceremonies, but the dark and cool, half-closed eyes of someone who justproved his point.On a bright Thursday afternoon shedding harsh light on Sacktor’s dingyDownstate laboratory, Research Assistant Professor Panayiotis Tsokas walks inwith a cage holding two large black and white rats, brought in pairs to relieve theirstress of being moved. One rat will live to see another day. Tsokas picks up theother. He places the rat in the bottom portion of a Culligan bottle cut in half,originally intended for a water cooler but now filled with an anesthetic gas. Heplaces a tin lid on top and weights the lid with the cover of an old steel oxygenbottle. The rat pushes its nose against the plastic, looking out to the lab filled withchemical bottles, arcane machinery and posters of Albert Einstein. It takes threesteps and falls to his side, relaxes gently until its breathing becomes barelyperceptible. Tsokas prepares a tiny guillotine by the lab sink.Meanwhile, sitting in his office, Sacktor stirs a test tube-shaped stainlesssteel tea infuser in a mug of hot water. His Society for Neuroscience plaque hangsnear the door, neither hidden nor highlighted. As the leader of his lab, Sacktornever touches the experiments. His job is to think – to ask new questions andexamine results. He says what Tsokas is about to do requires such precision andspeed that it takes about nine months to master. The goal is to harvest the rat’shippocampus, a section of the brain essential to most kinds of memories. Sacktoris not finished making his point about PKMzeta, the memory molecule. Knowingwhat retains memory might give scientists the clues needed to track specific
memories forming in the brain – that’s what Sacktor is after these days. It also willfurther prove his theory, sink his discovery deeper into the realm of acceptedwisdom about memory. Tsokas, an associate professor at Downstate, pulls out the unconscious rat,slides its head beneath the hovering blade and with one firm press of theguillotine gate beheads the animal. Now it’s a race. He grabs scissors to split thescalp and skull, then a scalpel to carefully but quickly extract the brain, whichbegins to decay almost immediately after death. Tsokas has minutes to extractthe hippocampus before that happens. He runs down the lab hall, brain in a smallcontainer, to a walk-in freezer where he expertly extracts the gelatinousmembrane, smaller than a baby pea. While dissecting, Tsokas talks about Sacktor.“He’s very open to ideas, he’s ready to try whatever you think might work.” Hedivides the hippocampus into thin sections with a miniature round-blade slicer,then races back to the lab, where he sets the hippocampus slices into a solutionthat mimics spinal fluid. Because he acted fast enough, the hippocampus willperform as if it were functioning in the brain for about a day. The slices will bestudied with a process called Long Term Potentiation, which delivers shocks to thehippocampus to study how the brain’s neural pathways respond. These shocks,many scientists believe, are roughly analogous to experiences that becomememories. When shocked, PKMzeta proliferates and takes on a life of its own.“I wish we didn’t have to kill animals,” Tsokas says over the morbid scene inthe sink, “but it’s going to help someone someday.”+Basic neuroscience does not necessarily search for cures to a disease, butrather for answers about the fundamental nature of the brain. This is Sacktor's job. Basic neuroscientists believe their work in the murky depths of neuralnetworks will someday surface as important to everyday life, but oftentimes theydon’t know exactly how.April 6, 2009 was one of those rare days when Sacktor watched his workemerge in the real world. He sat in the kitchen of his Yonkers turn-of-the-centuryshingle house reading the Monday
New York Times
with more than a passinginterest – his name was on the front page above the fold, under the article, “So You Just Want to Forget? Science is Working on an Eraser.” The article reportedhow Sacktor’s team was able to erase a living rat’s memory without damaging thebrain. “The discovery of such an apparently critical memorymolecule,”
writer Benedict Carey wrote of Sacktor’s work, “and its manypotential uses, are part of the buzz surrounding a field that, in just the past fewyears, has made the seemingly impossible suddenly probable: neuroscience, thestudy of the brain.”

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