1. Consolidation of Memories
Psychology 355: Cognitive Psychology Instructor: John Miyamoto 05/05/2016: Lecture 06-4
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2. Lecture probably ends here
Outline
Consolidation of memories
Standard model of consolidation (Alternative theory: The multiple trace model of consolidation)
Disruption of memory reconsolidation as a treatment for PTSD
Lecture probably ends here
Consolidation of Memories
Psych 355, Miyamoto, Spr ‘16

3. Consolidation of Memories
Recently created memories are typically fragile.
Without additional retrievals, they are often too weak to retrieve.
A concussion soon after learning can cause permanent loss of a memory.
Fragility of new memories implies that it takes cognitive processing after the initial experience to create a strong memory.
Goldstein, Figure Typical pattern of retrograde amnesia. The recent past is the least consolidated - it is the most likely to be lost. More distant past is more consolidated - it is more likely to be preserved.
Consolidation is the process by which a memory is transformed from an unstable state to a more permanent state.
What Is Happening During Consolidation?
Psych 355, Miyamoto, Spr '16

4. What Is Happening During Memory Consolidation?
Changes are happening at two levels:
Synaptic Consolidation: Repeated experience causes changes at the level of the synapse.
These changes occur quickly, over a matter of minutes.
Systems Consolidation: Repeated retrievals cause changes in the organization of neural circuits that represent memories.
These changes occur gradually, over days, months or even years.
Synaptic Changes During Learning – Long-Term Potentiation
Psych 355, Miyamoto, Spr '16

5. Synaptic Consolidation
Goldstein (2014), Figure 7.14, p. 194
1st Presentation of Stimulus
Continued Presentation of Stimulus
After Many Presentations of Stimulus
Structural Changes
Increased firing (LTP)
Long-Term Potentiation (LTP): Structural changes at synapse result in increased firing to the same stimulus.
Same Diagram without Emphasis Rectangles 5
Psych 355, Miyamoto, Spr '16

6. Synaptic Consolidation
Goldstein (2014), Figure 7.14, p. 194
1st Presentation of Stimulus
Continued Presentation of Stimulus
After Many Presentations of Stimulus
Structural Changes
Increased firing (LTP)
Long-Term Potentiation (LTP): Structural changes at synapse result in increased firing to the same stimulus.
System Consolidation - Long-Term Process of Memory Formation 6
Psych 355, Miyamoto, Spr '16

7. System Consolidation: The Time Course of Memory Formation
Figure 7.15 (p. 195) attempts to explain the role of the hippocampus in the encoding and consolidation of memories.
Hippocampus
Cortical Areas
Same Diagram – Emphasis Rectangle on Left
Psych 355, Miyamoto, Spr '16

8. The Time Course of Memory Formation
Initial Encoding of Current Experience
Hippocampus
Cortical Areas
Same Diagram – Emphasis Rectangle on Middle
Psych 355, Miyamoto, Spr '16

9. The Time Course of Memory Formation
Retrieval of Episodic Memory
Hippocampus
Cortical Areas
Same Diagram – Emphasis Rectangle on Right
Psych 355, Miyamoto, Spr '16

10. The Time Course of Memory Formation
Retrieval (After Much Learning) of Episodic Memory
Hippocampus
Cortical Areas
Transition to Diagrams That Show the Same Process But With Different Graphics
Psych 355, Miyamoto, Spr '16

11. The Standard Model of Memory Consolidation
The next slides display the same ideas as the preceding slides, but with more informative graphics.
The next set of slides show:
The Standard Model of Memory Consolidation
Explanation of Consolidation in terms of Brain Diagrams
Psych 355, Miyamoto, Spr '16

12. Encoding
1: Processing of current information activates different brain areas in occipital, parietal, temporal and frontal cortex.
Event or episode
This slide is based on instructional material that was downloaded from the Pearson Publishers website ( for Smith & Kosslyn (2006; ISBN ).
2: Multiple brain activations spread to hippocampus (convergence zone).
Somehow, hippocampus binds multimodal inputs together and encodes long-term memory.
Event or episode
Diagram of Brain Activity During Retrieval
Psych 355, Miyamoto, Spr '16

13. Retrieval
3: At time of recall, partial cues stimulate some brain areas that were also activated at encoding.
5: Somehow, the hippocampus triggers pattern completion (partial reactivation of original activation pattern).
Partial cue
4: Activation spreads to the hippocampus.
This slide is based on instructional material that was downloaded from the Pearson Publishers website ( for Smith & Kosslyn (2006; ISBN ).
Partial cue
Partial cue
Psych 355, Miyamoto, Spr '16
Same Diagram with Statement of Recapitulation Hypothesis

14. Retrieval Reactivation Hypothesis: (Goldstein, p. 195)
Episodic retrieval involves reinstatement of activations that were present during encoding.
Hippocampus plays an important role in reactivation.
This slide is based on instructional material that was downloaded from the Pearson Publishers website ( for Smith & Kosslyn (2006; ISBN ).
Psych 355, Miyamoto, Spr '16
Reactivation Before & After Consolidation

15. Standard Model of Consolidation:
Retrieval BEFORE consolidation has been completed.
Retrieval AFTER consolidation has been completed.
Multiple Trace Model of Consolidation
Psych 355, Miyamoto, Spr '16

16. Multiple Trace Model of Consolidation
Multiple trace model is opposed to the standard model of consolidation.
According to this model, the hippocampus is involved in retrieval of remote episodic memories as well as recent episodic memories, but only if they are not semanticized.
Semanticization of Episodic Memories & the Remember/Know Distinction
Hippocampus is active during retrieval of remote episodic memories that the subjects "remember", but not during the retrieval of memories that the subjects "know" are true, but don't "remember".
Intuitive ideas: Over time, memories can become facts (as opposed to retrieval of experiences). Retrieval of facts may not involve the hippocampus to the same degree as retrieval of experiences.
This is called the semanticization of memories (transformation of a memory from being episodic to being semantic).
Consolidation & Reconsolidation
Psych 355, Miyamoto, Spr '16

17. Consolidation & Reconsolidation
Fact to be discussed later in this lecture:
When a memory is retrieved, it is vulnerable to change.
After retrieval of a memory, it is necessary to store the memory again to return it to a permanent state.
Consolidation refers to processes that change an initially encoded memory into a permanent memory.
Reconsolidation refers to processes that restore a memory to a more permanent form after it has been retrieved.
Sometimes consolidation & reconsolidation are referred to together as “consolidation.”
Role of Sleep in Consolidation
Psych 355, Miyamoto, Spr '16

18. Interestingly Enough, .....
Sleep (dreaming?) plays a functional role in promoting consolidation.
Rat brain cells that fire together while exploring a location also show increased firing during subsequent sleep. Not true of other cells that did not fire during exploration.
Disruption of dreaming seems to disrupt consolidation.
Similar effects with humans who are learning to play tetris.
Some evidence suggests that if a subject expects to be tested on Topic A but not on Topic B, then sleep (possibly, dreaming) enhances future memory of Topic A more than Topic B.
Role of sleep in consolidation is not understood, but there seems to be a significant relationship between sleep and consolidation.
Goldstein isn’t clear about the distinction between consolidation and reconsolidation. It is certain that they are similar; are they identical?
The current literature doesn’t give a definite answer to this questions.
McKenzie, S., & Eichenbaum, H. (2011). Consolidation and reconsolidation: Two lives of memories? Neuron, 71,
Alberini, C. M. (2005). Mechanisms of memory stabilization: Are consolidation and reconsolidation similar or distinct processes? Trends in Neurosciences, 28(1),
Summary of Standard Model of Consolidation
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19. Summary re Standard Model of Consolidation
Consolidation & reconsolidation ...
... long-term memory representations become more stable over time;
... hippocampus plays a central role in retrieval of incompletely consolidated memories;
... over time, retrieval of memories becomes independent from the hippocampus and other medial temporal lobe activity.
Memory Representations are Malleable at Time of Retrieval
Psych 355, Miyamoto, Spr '16

20. Memories Representations Are Malleable At Time of Retrieval
Hypothesis: When memories are retrieved, they are vulnerable to change.
Under special circumstances, when memories are retrieved, memories can be altered, even wiped out.
Can these ideas be used to develop a treatment for PTSD?
Undoing Fear Conditioning in the Rat
Psych 355, Miyamoto, Spr '16

21. Undoing Fear Conditioning in the Rat
Nader, K., Schafe, G. E., & Le Doux, J. E. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature, 406,
If a tone is paired with an electric shock, a rat will learn to freeze when it hears the tone (classical conditioning of fear).
Anisomycin – antibiotic that inhibits protein synthesis that is required in the formation of new memories.
Administering anisomycin to a rat can cause it to fail to learn.
Experimental Design (Diagram of Rat Learning or Unlearning)
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22. Experimental Design
Condition 1: Day 1: Tone + Shock + anisomycin Day 2: No drug; no tone; no shock Day 3: Does not freeze to tone
(shows no learning)
Day Day Day 3
Condition 2: Day 1: Tone + Shock Day 2: Drug; no tone; no shock Day 3: Freezes to tone
(shows learning)
Day Day Day 3
Conditions 1 & 3: In both conditions, rats learned to freeze on Day 1.
Conditions 1 & 3: In both conditions, rats got anisomycin on Day 2.
But rats in Condition 1 did not forget their learning on Day 1. Rats in Condition 3 did forget their learning. Why?
Retrieval of learning on Day 2 made the learning from Day 1 vulnerable to loss (damage? unlearning?).
Spring 2014: Garret Zieve (student) pointed out that we need one more condition:
Condition *4*:
Day 1: Tone + Shock
Day 2: Tone (no shock)
Day 3: Test tone alone.
Need to verify that Day 2 tone alone does not extinguish the conditioning. You need Day 2 drug + tone (no shock) to decondiiton the rat.
5/20/2014: JM talked with Lauren Graham about Garret’s point. She says that the answer depends on the strength of the initial shock (stronger shock is harder to extinguish) and the number of extinction trials on Day 2, but if the Day 1 shock were strong enough and if there was only one extinction trial on Day 2, then indeed it would be well-known that without the drug on Day 2, the one extinction trial would not extinguish the fear conditioning from Day 2.
Condition 3: Day 1: Tone + Shock Day 2: Drug + tone, no shock. Day 3: Does not freeze to tone
(shows no learning)
Day Day Day 3
Figure 7.20
Repeat This Slide with Emphasis Rectangles
Psych 355, Miyamoto, Spr '16

23. Experimental Design
Condition 1: Day 1: Tone + Shock + anisomycin Day 2: No drug; no tone; no shock Day 3: Does not freeze to tone
(shows no learning)
Day Day Day 3
Condition 2: Day 1: Tone + Shock Day 2: Drug; no tone; no shock Day 3: Freezes to tone
(shows learning)
Day Day Day 3
Conditions 1 & 3: In both conditions, rats learned to freeze on Day 1.
Conditions 1 & 3: In both conditions, rats got anisomycin on Day 2.
But rats in Condition 1 did not forget their learning on Day 1. Rats in Condition 3 did forget their learning. Why?
Retrieval of learning on Day 2 made the learning from Day 1 vulnerable to loss (damage? unlearning?).
Spring 2014: Garret Zieve (student) pointed out that we need one more condition:
Condition *4*:
Day 1: Tone + Shock
Day 2: Tone (no shock)
Day 3: Test tone alone.
Need to verify that Day 2 tone alone does not extinguish the conditioning. You need Day 2 drug + tone (no shock) to decondiiton the rat.
5/20/2014: JM talked with Lauren Graham about Garret’s point. She says that the answer depends on the strength of the initial shock (stronger shock is harder to extinguish) and the number of extinction trials on Day 2, but if the Day 1 shock were strong enough and if there was only one extinction trial on Day 2, then indeed it would be well-known that without the drug on Day 2, the one extinction trial would not extinguish the fear conditioning from Day 2.
Condition 3: Day 1: Tone + Shock Day 2: Drug + tone, no shock. Day 3: Does not freeze to tone
(shows no learning)
Day Day Day 3
Figure 7.20
Summary of Results
Psych 355, Miyamoto, Spr '16

24. Summary of Main Finding
Condition 1: Day 1: Tone + Shock + anisomycin Day 2: No drug; no tone; no shock Day 3: Does not freeze to tone
(shows no learning)
Combining drug with tone & shock on Day 1 prevents fear conditioning.
Condition 2: Day 1: Tone + Shock Day 2: Drug; no tone; no shock Day 3: Freezes to tone
(shows learning)
Drug on Day 2 does not undo fear conditioning.
Conditions 1 & 3: In both conditions, rats learned to freeze on Day 1.
Conditions 1 & 3: In both conditions, rats got anisomycin on Day 2.
But rats in Condition 1 did not forget their learning on Day 1. Rats in Condition 3 did forget their learning. Why?
Retrieval of learning on Day 2 made the learning from Day 1 vulnerable to loss (damage? unlearning?).
Condition 3: Day 1: Tone + Shock Day 2: Drug + tone, no shock. Day 3: Does not freeze to tone
(shows no learning)
Combining drug with retrieval of fear conditioning on Day 2 undoes fear conditioning.
Retrieval Makes Day 1 Learning Vulnerable to Change
Psych 355, Miyamoto, Spr '16

25. Interpretation
Retrieval makes the fear conditioning from Day 1 vulnerable to change. Combining retrieval with drug prevents reconsolidation of memory of fear conditioning, thereby causing loss of conditioning.
Condition 3 displayed to the right:
Nader et al. (2000) state that the memory trace is "labile" during retrieval, i.e., its form can be changed at that time.
Day Day Day 3
Conditions 1 & 3: In both conditions, rats learned to freeze on Day 1.
Conditions 1 & 3: In both conditions, rats got anisomycin on Day 2.
But rats in Condition 1 did not forget their learning on Day 1. Rats in Condition 3 did forget their learning. Why?
Retrieval of learning on Day 2 made the learning from Day 1 vulnerable to loss (damage? unlearning?).
Using Fragility of Memories During Retrieval to Treat PTSD
Psych 355, Miyamoto, Spr '16

26. Note Added After the Lecture on Thursday 05/05/2016
The following slides pertaining to the treatment of PTSD are the same as the ones that were displayed in class, but an improved version of these slides will be presented on Monday 05/09/ You should use the Monday slides because they are more clear.
Psych 355,, Miyamoto, Spr '16

27. Using the Fragility of Memories During Retrieval to Treat PTSD
Brunet, A., Orr, S. P., Tremblay, J., Robertson, K., Nader, K., & Pitman, R. K. (2008). Effect of post- retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. Journal of Psychiatric Research, 42,
Post-traumatic stress disorder (PTSD): Strong fear and stress responses are evoked by reminders of the initial traumatic event.
Brunet et al. asked whether human PTSD patients can lose or at least diminish their fear and stress conditioning by techniques that are similar to Nader et al.'s demonstration that rats can lose their fear conditioning.
Study used propranolol, a drug that is used to prevent traumatic memories if administered immediately following a traumatic event. Propranolol reduces the fear & stress conditioning of trauma.
Propranolol will not reduce PTSD in someone who already has PTSD.
It was previously used to prevent PTSD. Administration of propranolol within several hours of a traumatic experience reduces physiological measures of fear and stress that accompany future retrieval of memories of the traumatic experience.
The Goldstein textbook contains a misprint. The drug is referred to as “probanolol” but it should be “propranolol.”
Brunet et al.'s Subjects Were PTSD Patients
Psych 355, Miyamoto, Spr '16

28. Brunet et al.'s Study of PTSD Subjects
PTSD patients: Childhood sexual abuse, motor vehicle accident, rape, being taken hostage.
Comorbid mental disorders included: major depressive disorder, panic disorder, social phobia, bulimia, generalized anxiety disorder.
Two scripts were prepared for each patient that described the events that produced the trauma for that patient.
19 PTSD patients were randomly assigned to either a treatment condition or a placebo control condition.
Both Conditions: Patient hears a 30-second recording describing their traumatic experience.
Treatment Condition: Patient is injected with propranolol immediately following recording.
Control Condition: Patient is injected with a placebo that has no active ingredients.
Related paper on use of corticosteroids to mitigate or block PTSD: E:\pprs\Neuro\ZoharJ Hydrocortisone After Trauma Alters Traj o PTSD.pdf
Test of Treatment - Was It Efficacious?
Psych 355, Miyamoto, Spr '16

29. Test of Treatment
One week later, the patients listened to a taped version of the scripts that described their traumatic experience, and are asked to imagine the traumatic events while listening to the tape.
Physiological measures of stress and anxiety are taken while patients listen to the tape.
Question: When the patients hear the taped version of traumatic experience, will they experience fear, anxiety, etc. of PTSD?
I.e., has the drug treatment reduced or eliminated their tendency to associate fear responses with these memories.
Analogy Between Rat Conditioning and PTSD Treatment
Psych 355, Miyamoto, Spr '16

30. Analogy Between PTSD Treatment & Conditioning
HUMAN RAT
Traumatic experience Tone + shock conditioning in the rat
Listen to taped Rat hears tone without the shock description of traumatic experience
Injection of propranolol Injection of anisomycin immediately after recall immediately after rat hears tone
Later, will the human seem to have unlearned the fear conditioning to the traumatic memories?
Later, the rat seems to have unlearned the fear conditioning to the tone.
Experimental Results
Psych 355, Miyamoto, Spr '16

31. Grey = placebo group; Black = propranolol group
Brunet et al. Results
Tensing of Frowning Muscles
Heart Rate Skin Conductance Corrugator EMG
Y-Axis Are Z-Scores Relative to Base Rate
Patients report symptom improvement.
Grey = placebo group; Black = propranolol group
Result: Therapy reduces original fear conditioning.
Return to Malleability of Memory During Retrieval
Psych 355, Miyamoto, Spr '16

32. Grey = placebo group; Black = propranolol group
Brunet et al. Results
Tensing of Frowning Muscles
Heart Rate Skin Conductance Corrugator EMG
Y-Axis Are Z-Scores Relative to Base Rate
Patients report symptom improvement.
Grey = placebo group; Black = propranolol group
Result: Therapy reduces original fear conditioning.
Return to Malleability of Memory During Retrieval
Psych 355, Miyamoto, Spr '16

33. Thursday, May 05, 2016: The Lecture Ended Here
Psych 355,, Miyamoto, Spr '16

34. Malleability of Memories During Retrieval
Learned associations can be lost during retrieval
Rats unlearned tone-shock connection
Humans unlearn (to some degree) the association between a traumatic episodic memory and the emotional response
Consolidation & Reconsolidation – memories can be strengthened during retrieval
Practice testing (retrieval) produces better future recall
Do these results contradict each other?
Stored representations can change during retrieval.
Usually the change makes the memory stronger, better organized, more linked to other memories, especially to retrieval cues.
The opposite can also happen, e.g., rats unlearn their fear conditioning, or humans become desensitized to memories of trauma. This special case is based on the injection of drugs that would not normally be present.
No!
Conclusions re Consolidation – END
Psych 355, Miyamoto, Spr '16

35. Conclusion re Consolidation
Consolidation occurs through reactivation of memories, followed by re-encoding of the memories.
Hippocampus plays a major role in reactivation for recent memories. After the memories have been consolidated, the hippocampus plays a reduced role in retrieval of memories.
Memories are malleable during or shortly after retrieval.
END
Psych 355, Miyamoto, Spr '16