Transcript Stress-Induced Out-of-Context Activation of Memory

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
Introduction
• Inappropriate recollections and responses in
stressful conditions are hallmarks of posttraumatic 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 1a—Appetitive left/right discrimination training
(B) Experiment 1b—Circulating 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 2a—Aversive left/right discrimination training
(D) Experiment 2b—Experiment 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 3a—Aversive left/right discrimination training using the intensive
training protocol (+ 30 trials). Retention was tested on Day 3 by reversal learning.
(F) Experiment 3b—Rats 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 4—Electro-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 5—Propranolol, blocker of the adrenergic component of
stress, caused amnesia of inhibitory avoidance memory only if it was
administered after the forced swim.
(B) Experiment 6—Dexamethasone, 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 7—Swim-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 8a—Bilateral TTX inactivation of dorsal hippocampus in the D1TTX group (1 h before learning) did not influence left/right discrimination
learning in the Y-maze task compared with saline controls
(B) Experiment 8b—The 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 9—Hippocampus was necessary for the swim-induced
enhancement of memory.
Experiment 10—The 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 swiminduced 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.
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