Why Emotionally Charged Events Are So Memorable

"This phenomenon is something everyone can identify with," said Roberto Malinow of the Cold Spring Harbor Laboratory in New York. "You can probably remember where you were when you heard about 9/11, but you probably don't know where you were on 9/10. We've identified one mechanism that may underlie this effect."

The parts of the brain where memories are stored need to distinguish between significant experiences and those that carry less importance, giving priority to the transformation of the former into long-term memory, the researchers explained.

One factor that scientists believe to be critical in that process is the emotional load of an event. Indeed, studies have shown that heightened states of emotion can facilitate learning and memory. In some situations, this process can even become pathological, Malinow said, as occurs in posttraumatic stress disorder (PTSD), a condition characterized by persistent vivid memories of traumatic events.

In a report in Cell, Johns Hopkins researchers and their collaborators at Cold Spring Harbor and New York University have identified the likely biological basis for this: a hormone released during emotional arousal "primes" nerve cells to remember events by increasing their chemical sensitivity at sites where nerves rewire to form new memory circuits.

Describing the brain as a big circuit board in which each new experience creates a new circuit, Hopkins neuroscience professor Richard Huganir, Ph.D. says that he and his team found that during emotional peaks, the hormone norepinephrine dramatically sensitizes synapses -- the site where nerve cells make an electro-chemical connection -- to enhance the sculpting of a memory into the big board.

Norepinephrine, more widely known as a "fight or flight" hormone, energizes the process by adding phosphate molecules to a nerve cell receptor called GluR1. The phosphates help guide the receptors to insert themselves adjacent to a synapse. "Now when the brain needs to form a memory, the nerves have plenty of available receptors to quickly adjust the strength of the connection and lock that memory into place," Huganir says.

Huganir and his team suspected that GluR1might be a target of norepinephrine since disruptions in this receptor cause spatial memory defects in mice. They tested the idea by either injecting healthy mice with adrenaline or exposing them to fox urine, both of which increase norepinephrine levels in brain. Analyzing brain slices of the mice, the researchers saw increased phosphates on the GluR1 receptors and an increased ability of these receptors to be recruited to synapses.

When the researchers put mice in a cage, gave a mild shock, took them out of that cage and put them back in it the next day, mice who had received adrenaline or fox urine tended to "freeze" in fear -- an indicator they associated the cage as the site of a shock -- more frequently, suggestive of enhanced memory.

However, in a similar experiment with mice genetically engineered to have a defective GluR1 receptor that phosphates cannot attach to, adrenaline injections had no effect on mouse memory, further evidence of the "priming" effect of the receptor in response to norepinephrine.

The researchers plan on continuing their work by going in the opposite direction and engineering another mouse strain that has a permanently phosphorylated or "primed" receptor. "We're curious to see how these mice will behave," Huganir says. "We suspect that they'll be pretty smart, but at the same time constantly anxious."

 Reference: Hu et al.: "Emotion Enhances Learning via Norepinephrine Regulation of AMPA-Receptor Trafficking." Publishing in Cell 131, 160--173, October 5, 2007. DOI 10.1016/j.cell.2007.09.017

Authors on the paper are Hailan Hu, Eleonore Real, and Roberto Malinow of Cold Spring Harbor Laboratory; Joe LeDoux of New York University; and Kogo Takamiya, Myoung-Goo Kang, and Huganir of Johns Hopkins.

The research was funded by the National Institutes of Health, Damon Runyon Postdoctoral Fellowship, NARSAD, and the Ale Davis and Maxine Harrison Foundation