Activating False Fear Highlights a Memory's Neural Trace

New research sheds light--literally--on recall mechanisms


The difference between false memories and true ones is the same as for jewels: it is always the false ones that look the most real, the most brilliant.

THIS QUOTE by surrealist painter Salvador Dalí comes to mind when pondering the latest wizardry coming out of two neurobiology laboratories. Before we come to that, however, let us remember that ever since Plato and Aristotle first likened memories to impressions made onto wax tablets, philosophers and natural scientists have searched for the physical substrate of memories. In the first half of the 20th century, psychologists carried out carefully controlled experiments to look for the so-called memory engram in the brain.

One of the most influential was Karl Lashley of Harvard University. He trained rats to run through mazes, turning left here and right over there, to find bits of food. Lashley would then make lesions in various parts of their cerebral cortex, the highly convolved sheet of neurons crowning the brain and situated just underneath the skull. He crystallized the insights he obtained in his lifelong efforts in two maxims. His principle of mass action stipulated that the cerebral cortex is holistically involved in memory storage. That is, the more cortex that is destroyed, the worse the memory of the animal, with no regard to what specific part of the cortex is removed. Indeed, according to Lashley's second principle, of equipotentiality, any area of cortex can substitute for any other region as far as learning is concerned.

The most singular feature of science that distinguishes it from other human activities, such as art or religion, and gives it a dynamics all its own is progress. It results from the steady and cumulative accumulation of knowledge, the emendation and cleansing of inaccuracy and inconsistency, and the understanding that comes from constantly querying nature through empirical investigation coupled with theory. In the case of the physical substrate of memories, today's neuroscience research has turned Lashley's two principles on their head. We now know that certain brain structures, such as the hippocampus, are involved in specific types of memory. Lose that region on both sides of the brain, such as the unfortunate patient HM did [see “Mind in Pictures,” on page 76], and you will not be able to form new explicit memories, whereas losses of large swaths of visual cortex leave the subjects blind but without memory impairments.

Yet percepts and memories are not born of brain regions but arise within intricate networks of neurons, connected by synapses. Neurons, rather than chunks of brain, are the atoms of thoughts, consciousness and remembering.

Implanting a False Memory in Mice

If you have ever been the victim of a mugging in a desolate parking garage, you may carry that occurrence with you to the end of your days. Worse, whenever you walk into a parking structure, you become anxious, your heart rate goes up and you begin to sweat. You have been fear-conditioned by the event. Fear conditioning has proved to be a fruitful avenue into the molecular and neuronal basis of learning and remembering. Mice, the experimental animals of choice, can easily be fear-conditioned by placing them in one particular environmental context—say, a chamber with black walls, white floor, dim lighting and the smell of vinegar—and applying brief electrical shocks to the floor under their paws. If the mouse is returned to this cage the next day, it “freezes” in place, becoming totally immobile for a fraction of a minute or longer, in anticipation of another shock. Freezing is an instinctual reaction to threats, as most predators are wired to look for movements to pinpoint their next meal. Put the mouse into an environment that looks and smells different from the one it was conditioned in, and much less freezing occurs.

Two American teams of researchers, one at the Massachusetts Institute of Technology led by Susumu Tonegawa and a second one under Mark Mayford of the Scripps Research Institute in La Jolla, Calif., exploited this standard test to manipulate the engram for this scary event. Part of the engram is found in the dentate gyrus (DG), a substructure of the hippocampus, in the M.I.T. study, whereas the Scripps study did not specify the location of the engram. Shocking an animal in one context will activate a small subset of DG neurons, around 2 to 4 percent. A different context will be encoded by a separate sparse group of DG cells. The electrical activity in these cells triggers the expression of a small number of so-called immediate early genes.

This article was originally published with the title "Searching for the Memory."

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