Neuroscientists have long viewed memory as a kind of neural architecture, a literal physical reshaping of the microstructure of the brain. In the 19th century, the pioneering neuroanatomist Santiago Ramón y Cajal theorized that information was processed in our heads each time an electrical impulse traveled across a synapse, the gap between one nerve cell and the next. Memories were made or altered, he proposed, when structures near the synapse changed.
More than a century later, the textbook description of episodic memory (conscious knowledge of an event) is a more sophisticated version of that same basic idea. Memory formation requires an elaborate chemical choreography of more than a hundred proteins, but the upshot is that sensory information, coded as electrical pulses, zips through neural networks of the brain. The impulses cause glutamate (one of the brain’s main neurotransmitters) to pop out of one nerve cell and travel across the synapse to activate the next by binding to its receptors, chemically active signaling stations on the cell surface. Ultimately the electrical and chemical signals reach the centers of memory, the almond-size amygdala and the banana-shaped hippocampus, adjacent structures buried on either side of the brain.
Neuroscientists believe that memory forms when neurons in these key brain structures are simultaneously activated by glutamate and an electrical pulse, a result of everyday sensory experience. The experience triggers a biochemical riot, causing a specialized glutamate receptor, called NMDA, to spring open and allow calcium ions to flood the cells. The ions stimulate dozens of enzymes that reshape the cells by opening up additional receptors and by prompting the formation of more synapses and new protrusions that contain still more receptors and synapses. In aggregate, these changes make neurons more sensitive to each other and put the anatomical scaffold of a memory in place.
Enacting all these changes takes time, and for up to a few hours the memory is like wet concrete—solidifying but not quite set, still open to interference. Once the process is over, though, the memory is said to be “consolidated.” In the textbook description, neuroscientists talk of memory the way geoscientists describe mountains—built through a dynamic process, but once established almost impossible to reshape quickly except by extraordinary means. By the late 1990s, this explanation of memory was so widely accepted by neuroscientists that its major author, Columbia University neuroscientist Eric Kandel, was awarded the Nobel Prize. It seemed that the most important questions about memory had been answered.
No wonder, then, that Nader—at the time a young postdoc studying the neurobiology of fear at New York University—was electrified when he attended one of Kandel’s lectures.