Stress-Induced Out-of-Context Activation of Memory

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Stress-Induced Out-of-Context Activation of Memory

• Karel Jezek, Benjamin B. Lee, Eduard Kelemen,
  Katharine M. McCarthy, Bruce S. McEwen, Andre A.
• Fenton
• PLOS BIOLOGY December 2010

ZHANG Zicong, Feb 14, 2011
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Introduction

• Inappropriate recollections and responses in
  stressful conditions are hallmarks of
  post-traumatic stress disorder (PTSD) and other
  anxiety and mood disorders, but how stress
  contributes to the disorders is unclear.
• The possibility that stress itself might promote
  inappropriate associations between unrelated
  memories and events has not been explored.
• The authors demonstrate that a single stressful
  experience can activate already consolidated
  memories outside of their appropriate context.

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Section 1
(A) Experiment 1aAppetitive left/right
discrimination training
(B) Experiment 1bCirculating corticosterone
levels in trunk blood at different stages of
repeated experiment 1a were collected
Summary Stressful forced swim enhanced the
expression of 24-h-old memory.
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Section 1
(C) Experiment 2aAversive left/right
discrimination training (D) Experiment
2bExperiment 2a was repeated, extending the
interval between swim and the retention test to 6
d
Summary The enhancement of the expression of
memory did not depend on whether learning was
appetitive or aversive. The memory enhancement
was long lasting for at lease 6 d.
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Section 1
(E) Experiment 3aAversive left/right
discrimination training using the intensive
training protocol ( 30 trials). Retention was
tested on Day 3 by reversal learning. (F)
Experiment 3bRats were forced to swim 24h before
intensive training to examine whether swim
impairs learning abilities.
Summary Memory acquired on Day 1 interfered
reversal learning on Day 3. Stressful swim
enhanced Day 1 memory, resulting in higher errors
in reversal learning. Swim neither improved nor
impaired the ability to learn the task.
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Summary of Section 1

• Stressful forced swim enhanced the expression of
  memory.
• The phenomenon is robust, persisting at least 6
  d.
• It was observed for both aversive and appetitive
  conditioning, for weak and strong memories, and
  whether memory was assessed by extinction or
  reversal tests.
• Whether the day-old memory is undergoing cellular
  consolidation at the time of swim?

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Section 2
Experiment 4Electro-convulsive shock (ECS)
blocked the swim-induced enhancement of memory.
In ECS or delECS (5h) group, ECS was delivered
immediately or 5 h after swim. ECS amnesic
treatment
Summary The results suggest that the swim
activated a stable memory, making it transiently
sensitive to amnestic treatment ECS.
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Section 2
(A) Experiment 5Propranolol, blocker of the
adrenergic component of stress, caused amnesia of
inhibitory avoidance memory only if it was
administered after the forced swim. (B)
Experiment 6Dexamethasone, a potent suppressant
of the hypothalamic-pituitary-adrenal (HPA) axis,
blocks the swim-induced enhancement of memory.
Summary Activation of both the adrenergic and
HPA components of stress are crucial for the
phenomenon.
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Section 2
Experiment 7Swim-induced interhemispheric
transfer (IHT) of lateralized memory. The
training protocol is administered under
unilateral cortical spreading depression (CSD)
(shading), which led to the formation of a
lateralized memory. The IHT only occurred in
Lat-Sw group.
Summary The swim modified discrimination memory
by enhancing its expression, by switching it from
a consolidated to a labile state, and by
modifying what part of the brain could retrieve
it, a progress thought to require
synapse-specific plasticity.
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Summary of Section 2

• Stressful swim made conditioned avoidance
  susceptible to amnestic treatment, and activation
  of both adrenergic and HPA components of stress
  are crucial for the phenomenon.
• Stressful swim activated memory.
• OCAM Out-of-Context activation of memory.
• The triggering experience did not need to have
  any physical contextual elements in common with
  the experience of the memory encoding or
  retrieval.
• Hippocampal dysfunction impairs episodic encoding
  and recall. Whether is the hippocampus necessary
  for OCAM?

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Section 3
(A) Experiment 8aBilateral TTX inactivation of
dorsal hippocampus in the D1-TTX group (1 h
before learning) did not influence left/right
discrimination learning in the Y-maze task
compared with saline controls
(B) Experiment 8bThe TTX injection did not
impair retrieval.
Summary Acquisition and retrieval of left/right
discrimination does not depend on dorsal
hippocampus.
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Section 3
(C) Experiment 9Hippocampus was necessary for
the swim-induced enhancement of
memory. Experiment 10The swim-induced
inter-hemispheric transfer of lateralized memory
required hippocampal function.
Summary Swim-induced memory enhancement and IHT
of lateralized memory requires hippocampus
function.
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Summary of Section 3

• Left/right discrimination memory could be
  acquired and recalled independently of the
  hippocampus.
• The hippocampus was necessary for the
  swim-induced memory enhancement.
• OCAM required a functional hippocampus during the
  swim.

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Discussion

• OCAM affects memory storage rather than its
  retrieval.
• Whether is stress-induced activation of memory
  biochemically identical to consolidation and
  reconsolidation?
• The hippocampus modifies recent memories that are
  stored elsewhere in the brain and is a site along
  with amygdala for the combined roles of stress
  and arousal in mediating memory modulation.

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Hypothesis

• Stress-triggered memory activation creates a
  condition where multiple memories coactivate, and
  through mechanisms of synaptic plasticity that
  include both long-term potentiation and
  depression, consolidation and reconsolidation,
  their subsequent expression is enhanced.