The EST/Sloan Project is committed to “challenge and broaden the public’s understanding of science and technology and their impact on our lives.” In that spirit, we offer this essay on the neuroscience behind what you are now by Sam Chanse, the 2022 EST/Sloan mainstage production. what you are now began previews on March 10 and runs through April 3. You can purchase tickets here.
The Neuroscience Behind what you are now
By Rich Kelley, Science Press Liaison
“Memory is a marvelous device, a means of transporting ourselves to earlier times. We can go back a moment, or most of a life. But as we all know, it’s not perfect, and is certainly not literal. It’s a reconstruction of facts and experiences on the basis of the way they were stored, not as they actually occurred. And it’s a reconstruction by a brain that is different from the one that formed the memory.” —Joseph LeDoux
A quick review of the metaphors we have used for memory reveals how far we have come—and how inadequate we are at describing it: from wax tablet to library to labyrinth to enchanted loom to switchboard to network to leaky bucket to computer program to hologram. From a scientific standpoint, what has changed our thinking about memory has usually come from an experiment. WHAT YOU ARE NOW refers to several significant experiments in the history of neuroscience. We thought you might find this background information on some of them interesting.
Ivan Pavlov (1849‒1936) was a Russian physiologist best known for inventing what has come to be known as “classical conditioning.” To study the physiology of the digestive system, Pavlov invented surgical procedures to create fistulas and gastric pouches on unanesthetized dogs so that he could repeat experiments for months and measure secretions outside the body. During his research Pavlov noticed that the dogs salivated when they saw the person who fed them. This led to his famous experiment: if he played a sound—usually on a metronome, not a bell—just when the food was put in the dog’s mouth, the dog would salivate at the sound, even when the food did not follow. This association turned a previously neutral stimulus—the tone—into a “conditioned” stimulus that generated a “conditioned” response—the salivating. Pavlov called the saliva thus generated “psychic secretions.” The power of the stimuli depended on conditions. If the tone was sounded repeatedly without the dog being fed, the salivating would decrease and eventually stop completely.
One of Pavlov's dogs with a surgically implanted cannula to measure salivation, preserved in the Pavlov Museum in Ryazan, Russia.
American behavioral psychologists favored Pavlov’s procedure because it removed any question of will, subjective experience, or consciousness from their experiments. Yet Pavlov himself never denied the inner life of his experimental animals. As Daniel Todes notes in his biography of Pavlov, “[Pavlov} identified them as heroes and cowards, intelligent and obtuse, independent and compliant, sociable and aloof, freedom fighters and narrow pragmatists.”
Eric Kandel (1929‒ ) is an Austrian-born American medical doctor, psychiatrist, neuroscientist, and professor of biochemistry who won the Nobel Prize in Physiology and Medicine in 2000 for his work on the physiological basis of memory storage in neurons. Kandel is perhaps best known for his insight that learning processes are similar among all life forms and that he could more easily study what changes occur in the synaptic connections between neurons during learning and memory storage by electrophysical analysis of an invertebrate as simple as a sea slug. He published his initial findings in 1963 and over the next twenty years his work in molecular neural science led to several remarkable findings, including that short-term memory involved functional changes in existing synapses but long-term memory involves a change in the number of synaptic connections.
A mouse in a glass container partially filled with water, as part of a forced-swimming test. The use of forced swimming tests is criticized by animal rights groups, notably PETA. (Photo: TaoPan CC3.0)
Learned safety in mice. The play refers to one of Kandel’s experiments with Daniela D. Pollak in which they conditioned mice to feel safe in stressful situations. Kandel called this conditioned inhibition of fear “learned safety.” For fear conditioning they associated an auditory tone with a shock to the mouse’s foot. For safety conditioning, the tone was not followed by a shock. The safety conditioned mice learned to associate the tone with the absence of danger and showed less anxiety, The mice were then given a stress test and put into a pool of water for a swim test. As Kandel explained, “In this seemingly desperate situation—where the mice have no option to escape from the water—they start to show signs of behavioral despair that are ameliorated by antidepressant medications. We found that the mice trained for safety could overcome their sense of hopelessness in the swim test.”
Memory reconsolidation. Memories evolve over time and “consolidation” and “reconsolidation” have come to describe the “two lives” memories have after the initial coding of new information. Consolidation refers to the extended period after learning when new information gets “fixed” at a cellular level and interleaved with existing memories. Much of consolidation is now thought to occur during sleep. Reconsolidation describes the process in which a newly consolidated memory gets modified as it is reactivated. In 2000 neuroscientists Karim Nader, Glenn E. Schafe and Joseph E. LeDoux performed an experiment to test whether it is possible to extinguish a “new memory” so that it never becomes a long-term memory. Current models of learning at the time proposed that new proteins need to be produced for recent experiences to be encoded into long-term memory. In the experiment, rats were conditioned to fear a tone by being given a foot shock. When they heard the tone, they froze into immobility. Twenty-four hours later, the rats were played the tone but given an infusion of anisomycin, a drug that inhibits protein synthesis, into the amygdala. Twenty-four hours later, when the rats which had been given the drug were played the tone, they didn’t freeze. They had lost the memory of the conditioning. This group was tested for up to 14 days and still had no memory of the conditioned response. A test group was given anisomycin without the tone being played. Twenty-four hours later, when they were played the tone, they still froze. In order for the conditioned response to be extinguished, the memory had to be reactivated—the tone had to be played—for the drug to interfere with memory retrieval.
A diagram representing a common understanding of memory systems (Image: Erich Parker)
Extinguishing traumatic memories. Drugs had been used successfully to remove traumatic memories but neuroscientist Daniela Schiller wondered if a non-invasive behavioral technique could be used instead. In 2010 she used classical conditioning to train 65 people to fear a colored square by associating it with a shock. Twenty four hours later, the sight of the square alone induced a fearful reaction in all of them. Schiller then divided them into three groups and presented the squares to one group many more times without a shock. Because this extinction process began within ten minutes of having their memory reactivated, the members of this group completely forgot their fear. A second group, which did not begin the extinction process until six hours after they were shown the squares, did not lose their fear. The experiment demonstrated that memories can be changed behaviorally and that interfering with memory reconsolidation can be effective but is very time sensitive. As Schiller commented in Michael Specter’s profile of her in The New Yorker, her work led her to realize that memory is “what you are now, not what you think you were in the past. When you change the story you created, you change your life.”
