Stress-Induced Out-of-Context Activation of Memory

1. Stress-Induced Out-of-Context Activation of Memory KarelJezek, Benjamin B. Lee, Eduard Kelemen, Katharine M. McCarthy, Bruce S. McEwen, Andre A. Fenton PLOS BIOLOGY | December 2010 ZHANG Zicong, Feb 14, 2011

2. 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.

3. 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.

4. 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.

5. 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.

6. 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?

7. 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.

8. 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.

9. 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.

10. 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?

11. Section 3 (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.

12. 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.

13. 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.

14. 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.

15. 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.