Readings

What is memory consolidation?

1. Solidification of memory through protein synthesis

2. Previously thought to be final, but now we know we can modify

What is memory reconsolidation?

1. Stored memories retrieved

2. Become temporarily destabilised + active for modification

3. Need protein synthesis again

4. Long-term storage

How was memory reconsolidation discovered?

1. Fear-shock memory training in rats
2. Anisomycin (protein synthesis inhibitor) administered post-retrieval (tone alone)
3. Reduced freezing to tone in rats the next day, so inhibitor blocked reconsolidation

What is extinction?

1. Presenting CS alone repeatedly
2. Learns new CS-no US association + fear reduces
3. But fear can return through renewal, reinstatement, spontaneous recovery
4. So not useful for exposure therapy (for disorders w/ deep roots in memory consolidation), but reconsolidation blockade may be

What are the challenges with reconsolidation research in humans?

1. ECT side effects, toxic protein synthesis inhibitors (but these are used in rodents)
2. Drugs currently being tested to combine w/ behavioural therapy

What is the retrieval-extinction paradigm?

1. Retrieval cue presented
2. Wait for time window to start (reconsolidation window, memory destabilises)
3. Extinction training
4. Updates original memory rather than creating new memory (which is competing memory hypothesis, new state created)
5. CS now predicts neutral outcome (no US)

Where has the retrieval-extinction paradigm been effective?

1. Drug + alcohol addiction in rats
2. Shock + spider phobias in humans, but limited

What are the factors influencing memory modification via reconsolidation?

1. Destabilisation
2. Timing
3. Prediction error
4. Strength, age, complexity of memory
5. Direction of change (bidirectional)
6. Duration of memory
7. Erasure
8. Neural circuits
9. Generalisability
10. Protein degradation

What about prediction error is important in reconsolidation?

1. Some believe necessary

difference between expectation + outcome

2. Gradual extinction better than regular extinction, so PE may not be necessary + might even inhibit learning

What conditions are important in consolidation?

1. When extinction conditions resemble those during acquisition - more likely to lead to updating
2. Very different conditions more likely to create new memory trace, not update original one

What about the strength, age and complexity of memories is important in reconsolidation?

1. Older, stronger + more complex = harder to modify (e.g. associative memories in networks)
2. Some evidence shows easier if retrieve + extinguish subcomponents of memory / combine w/ epigenetic manipulations

What about direction of change is important in reconsolidation?

1. When retrieved, memories can be strengthened, weakened or stay the same (bidirectionality)
2. Retrieve fear memory, aroused, incorporate physiological response into memory, strengthen the memory (if no other manipulation added)

What about the time window and erasure is important in reconsolidation?

1. Finite

6 hours in rats (varies across species)

2. Gradual memory modifications (updating of original memory trace), not erasure

What about CS and US specificity is important in reconsolidation?

1. Reconsolidation blockade only occurs for fear memories that were reactivated
2. Other memories remained intact
3. Sensory specific feature of stimulus encoded (e.g. shock to eye/foot) + selectively disrupted during reconsolidation
4. But potential to be generalisable

What about the duration of memory is important in reconsolidation?

1. Interferes w/ LTM while leaving STM intact
2. So effects of resconsolidation may not be seen right away, rather after 1 night of sleep
3. Robust + persistent effects in rodents

prevents return of conditioned response

What about erasure is important in reconsolidation?

1. Retrieval-extinction reduces fear, but does not erase it
2. Some fear behaviour remains after extinction via reinstatement

What about neural circuits is important in reconsolidation?

1. Different neural circuits for extinction + retrieval-extinction
2. Different patterns of neural expression
3. Different uses of medial prefrontal cortex + amygdala

What about destabilisation is important in reconsolidation?

1. Necessary

long interval needed to enable (otherwise, will be extinction)

2. Protein synthesis also necessary
3. No way to index if this has happened in humans

What about protein degradation is important in memory reconsolidation?

1. Protein degradation needed for reconsolidation
2. Retrieved memory must become destabilised, then only is it modifiable

What are the clinical applications of reconsolidation-based interventions?

1. Pharmacological blockage of reconsolidation - propranolol reduced PTSD symptoms (limited) - change may be more abrupt rather than gradual
2. Propranolol for spider phobia, persisting for 1 year + drug cravings
3. Behavioural updating during reconsolidation

What are the challenges of the consolidation approach?

1. Limitations in replications
2. Boundary conditions unclear
3. Translation of rodent to human studies unclear
4. Type of memory should be considered

What is memory consolidation?

1. Solidification of memory through protein synthesis
2. Previously thought to be final, but now we know we can modify

What is memory reconsolidation?

1. Stored memories retrieved
2. Become temporarily destabilised + active for modification
3. Need protein synthesis again
4. Long-term storage

How was memory reconsolidation discovered?

1. Fear-shock memory training in rats
2. Anisomycin (protein synthesis inhibitor) administered post-retrieval (tone alone)
3. Reduced freezing to tone in rats the next day, so inhibitor blocked reconsolidation

What is extinction?

1. Presenting CS alone repeatedly
2. Learns new CS-no US association + fear reduces
3. But fear can return through renewal, reinstatement, spontaneous recovery
4. So not useful for exposure therapy (for disorders w/ deep roots in memory consolidation), but reconsolidation blockade may be

What are the challenges with reconsolidation research in humans?

1. ECT side effects, toxic protein synthesis inhibitors (but these are used in rodents)
2. Drugs currently being tested to combine w/ behavioural therapy

What is the retrieval-extinction paradigm?

1. Retrieval cue presented
2. Wait for time window to start (reconsolidation window, memory destabilises)
3. Extinction training
4. Updates original memory rather than creating new memory (which is competing memory hypothesis, new state created)
5. CS now predicts neutral outcome (no US)

Where has the retrieval-extinction paradigm been effective?

1. Drug + alcohol addiction in rats
2. Shock + spider phobias in humans, but limited

What are the factors influencing memory modification via reconsolidation?

1. Destabilisation
2. Timing
3. Prediction error
4. Strength, age, complexity of memory
5. Direction of change (bidirectional)
6. Duration of memory
7. Erasure
8. Neural circuits
9. Generalisability
10. Protein degradation

What about prediction error is important in reconsolidation?

1. Some believe necessary

difference between expectation + outcome

2. Gradual extinction better than regular extinction, so PE may not be necessary + might even inhibit learning

What conditions are important in consolidation?

1. When extinction conditions resemble those during acquisition - more likely to lead to updating
2. Very different conditions more likely to create new memory trace, not update original one

What about the strength, age and complexity of memories is important in reconsolidation?

1. Older, stronger + more complex = harder to modify (e.g. associative memories in networks)
2. Some evidence shows easier if retrieve + extinguish subcomponents of memory / combine w/ epigenetic manipulations

What about direction of change is important in reconsolidation?

1. When retrieved, memories can be strengthened, weakened or stay the same (bidirectionality)
2. Retrieve fear memory, aroused, incorporate physiological response into memory, strengthen the memory (if no other manipulation added)

What about the time window and erasure is important in reconsolidation?

1. Finite

6 hours in rats (varies across species)

2. Gradual memory modifications (updating of original memory trace), not erasure

What about CS and US specificity is important in reconsolidation?

1. Reconsolidation blockade only occurs for fear memories that were reactivated
2. Other memories remained intact
3. Sensory specific feature of stimulus encoded (e.g. shock to eye/foot) + selectively disrupted during reconsolidation
4. But potential to be generalisable

What about the duration of memory is important in reconsolidation?

1. Interferes w/ LTM while leaving STM intact
2. So effects of resconsolidation may not be seen right away, rather after 1 night of sleep
3. Robust + persistent effects in rodents

prevents return of conditioned response

What about erasure is important in reconsolidation?

1. Retrieval-extinction reduces fear, but does not erase it
2. Some fear behaviour remains after extinction via reinstatement

What about neural circuits is important in reconsolidation?

1. Different neural circuits for extinction + retrieval-extinction
2. Different patterns of neural expression
3. Different uses of medial prefrontal cortex + amygdala

What about destabilisation is important in reconsolidation?

1. Necessary

long interval needed to enable (otherwise, will be extinction)

2. Protein synthesis also necessary
3. No way to index if this has happened in humans

What about protein degradation is important in memory reconsolidation?

1. Protein degradation needed for reconsolidation
2. Retrieved memory must become destabilised, then only is it modifiable

What are the clinical applications of reconsolidation-based interventions?

1. Pharmacological blockage of reconsolidation - propranolol reduced PTSD symptoms (limited) - change may be more abrupt rather than gradual
2. Propranolol for spider phobia, persisting for 1 year + drug cravings
3. Behavioural updating during reconsolidation

What are the challenges of the consolidation approach?

1. Limitations in replications
2. Boundary conditions unclear
3. Translation of rodent to human studies unclear
4. Type of memory should be considered

What is the hierarchical / Jacksonian view of brain organisation and how does this apply to learning in rats?

1. Levels of barin organisation
2. Lower + higher levels - lower levels = simplest (reflexive behaviours) + most tightly organised (less modifiable) + develop before higher centres (complex behaviours)
3. During ontogeny (development), brain matures in caudal to rostral manner (back to front)
4. Newborn rats have limited abilities to learn due to undeveloped sensory systems (e.g. eyes + ears shut at birth until 2 weeks later)
5. But can respond reflexively to sound + visual + taste cues few days before behavioural association can be learned
6. More developmental research uses simple behaviours + less known about more complex / higher behaviours

What are the 2 types of cues used in spatial behavior?

1. Proximal cues - within behavioural test location, stimuli occur w/ goal object to guide behaviour (goal object visible / audible)
2. Distal cues - environmental, learn about spatial location of goal relative to distal cues (goal object invisible / inaudible)

Explain experiment 1.

1. When can rats use proximal cues?
2. Location of platform varied randomly - platform either invisible + visible
3. At least 19 days old - use proximal cues + much faster for visible vs invisible
4. 17 day olds cannot

Explain experiment 2.

1. Is failure to use proximal cues because 17 day olds could not see objects above the water’s surface?
2. Visible platform had cone on top to make it more visible + varied platform location
3. Could use proximal cues better than previous experiment (latencies decreased over training)

Explain experiment 3.

1. When are rats capable of using distal cues?
2. Platform at fixed or varied location
3. Multiple measures - measured time in each quadrant, crossing quadrant previously containing object + pup’s head direction
4. 18-19 days old - little improvement for fixed / varied locations
5. 21-23 days old - improved over training through all 3 DVs

Explain the second part of experiment 3.

1. Unlikely to suddenly be able to use distal cues at 21 days and not 19 days, so tested 20 days
2. Found to be at transitional stage - spend equal time in training quadrant as older pups, but not searching as accurately / persistently (other 2 DVs same as younger pups)
3. Cannot use distal cues well (after proximal cue development)

Explain experiment 4.

1. Is this a sensory / perceptual problem?
2. Dark training context, except illuminated object hanging from ceiling (platform either under cup / varied quadrants)
3. 16 day olds - proximal cues did not help them find platform better, but helped older pups
4. 17-19 days old - used as a proximal cue

Explain experiment 5

1. Can rats use illuminated cup as distal-relational cue?
2. Platform either in fixed / varied locations
3. 17-19 days - no difference in fixed / random groups (18-19 days can use as a proximal, but not distal cue)
4. 22-23 days - used as distal-relational cue to find hidden platform

Explain experiment 6.

1. Cups not identified as specific cue used to solve problem
2. If not using cup as distal cue, 18 day olds using as a proximal cue is not relevant
3. Cups used as distal cue

What are the summarised findings?

1. Proximal + distal cues use different processes (dissociation due to ontogenic differences)
2. 17 day old rats used proximal (due to deficits in sensory-perceptual, motor, motivational / integrative components)
3. Only 20+ days old could use distal (22-23 very good)
4. Not sensory-perceptual issue (can see objects fine) + motivational/motor (17 day olds were fine on proximal tasks) that made 19 day olds fail on distal problem
5. Instead - different processes underlying proximal + distal cues, reflecting differences in development (not training variable / sensory-perceptual)
6. Aligns w/ Jacksonian perspective, as simple develops before complex