Both extensive psychological research and personal
experience confirm that events that happen
during heightened states of emotion — such as fear,
anger and joy — are far more memorable than less-
dramatic occurrences. In a report in the Oct. 5 issue of
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,
Johns Hopkins
neuroscience professor Richard Huganir said 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 said.
Huganir and his team suspected that GluR1 might be a
target of norepinephrine because
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 the 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 that 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 to which phosphates cannot attach, 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 said. "We suspect
that they'll be pretty smart but at the
same time, constantly anxious."
The research was funded by the National Institutes of
Health, Howard Hughes Medical
Institute, Damon Runyon Postdoctoral Fellowship, NARSAD,
and Ale Davis and Maxine Harrison
Foundation.
Authors on the paper are Hailan Hu, Eleonore Real and
Roberto Malinow, all of Cold Spring
Harbor Laboratory; Joe LeDoux, of New York University; and
Kogo Takamiya, Myoung-Goo Kang and
Huganir, all of Johns Hopkins.