Stress-Induced Out-of-Context Activation of Memory

Karel Jezek, Benjamin B. Lee, Eduard Kelemen, Katharine M. McCarthy, Bruce S. McEwen, Andre A.

FentonPLOS BIOLOGY | December 2010

ZHANG Zicong, Feb 14, 2011

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

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(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.

Section 1

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(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.

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

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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.

Section 2

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(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.

Section 2

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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.

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

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(A) Experiment 8a—Bilateral 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 8b—The TTX injection did not impair retrieval.

Summary: Acquisition and retrieval of left/right discrimination does not depend on dorsal hippocampus.

Section 3

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(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.

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.

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