People with anxiety disorders, such as post
traumatic stress disorder (PTSD), often experience
prolonged and exaggerated fearfulness. Now, an
animal study suggests that this might involve
disruption of a gradual shifting of brain circuitry
for retrieving fear memories.
Researchers funded by the National Institutes of
Health have discovered in rats that an old fear
memory is recalled by a separate brain pathway from
the one originally used to recall it when it was
fresh.
Although rats’ behavior did not change over time following fear conditioning, the underlying circuitry activated to retrieve the fear memory shifted, perhaps increasing its staying power. An initial circuit from the pre-limbic prefrontal cortex (PL) to the basolateral amygdala (BLA) was supplanted, a week later, by a circuit to the central amygdala (CeA) via the paraventricular nucleus of the thalamus (PVT). It’s thought that the PVT may serve to integrate fear with other adaptive responses. The discovery may provide clues to improved treatments for anxiety disorders. Source: Gregory Quirk, Ph.D., University of Puerto Rico School of Medicine.
"After rats were conditioned to fear a tone
associated with a mild shock, their overt behavior
remained unchanged over time, but the pathway
engaged in remembering the traumatic event took a
detour, perhaps increasing its staying power.
“While our memories feel constant across time, the
neural pathways supporting them actually change with
time,” explained Gregory Quirk, Ph.D. External Web
Site Policy, of the University of Puerto Rico School
of Medicine, in San Juan, a grantee of NIH’s
National Institute of Mental Health (NIMH).
“Uncovering new pathways for old memories could
change scientists’ view of post-traumatic stress
disorder, in which fearful events occur months or
years prior to the onset of symptoms.”
A research team led by Quirk and Fabricio Do-Monte,
D.V.M., Ph.D., report on their findings January 19,
2015, in the journal Nature.
Immediately after fear conditioning, a circuit
running from the prefrontal cortex, the executive
hub, to part of the amygdala, the fear hub, was
engaged to retrieve the memory.
But several days later, Quirk and colleagues
discovered that retrieval had migrated to a
different circuit – from the prefrontal cortex to an
area in the thalamus, called the paraventricular
region (PVT). The PVT, in turn, communicates with a
different central part of the amygdala that
orchestrates fear learning and expression.
The Quirk team spotted the moving memory using a
genetic/laser technique called optogenetics, which
can activate or silence specific pathways to tease
apart their workings.
The researchers say that the PVT may serve to
integrate fear with other adaptive responses, such
as stress, thereby strengthening the fear memory.
“In people with anxiety disorders, any disruption of
timing-dependent regulation in retrieval circuits
might worsen fear responses occurring long after a
traumatic event,” Quirk suggested.
In the same issue of Nature, NIMH grantees Bo Li,
Ph.D. External Web Site Policy, and Mario Penzo,
Ph.D. of Cold Spring Harbor Laboratory in New York,
and colleagues, reveal how the long-term fear memory
circuit works in mice to translate detection of
stress into adaptive behaviors.
Li and colleagues independently discovered the same
shift in memory retrieval circuitry occurring, over
time, after fear conditioning in mice. Using
powerful genetic-chemical, as well as optogenetic,
methods to experimentally switch pathways on and
off, they showed conclusively that neurons
originating in the PVT regulate fear processing by
acting on a class of neurons that store fear
memories in the central amygdala area.
The Li team traced this activity in the PVT to the
action of a messenger chemical, brain-derived
neurotrophic factor (BDNF), which has previously
been implicated in mood and anxiety disorders. For
example, altered BDNF expression has been linked to
PTSD.
BDNF from the PVT, working via a specific receptor,
activated the memory-storing amygdala neurons.
Simply infusing BDNF into the central amygdala area
caused mice to freeze in fear, suggesting that it
not only enables the formation of fear memories, but
also the expression of fear responses.
See also
Shedding new light on the formation of emotional
fear memories (2014-12-15)
Study shows how two brain areas interact to trigger
divergent emotional behaviors (2013-05-10)
For more information
Do-Monte HF, Quinones-Laracuente K, Quirk, GJ.
A temporal change in a circuits mediating retrieval
of fear memory.
Nature, Jan. 19, 2015.
DOI: 10.308/nature14030
Penzo MA, Robert V, Tucciarone J, De Bundel D, Wang
M, Van Aeist L, Varvas M, Parada LF, Palmiter R, He
M, Huang ZJ, Li B.
The paraventricular thalamus controls a executive
amygdala fear circuit.
Nature, Jan. 19, 2015.
DOI: 10.1038/nature13978
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