week 8 - memory reconsolidation and consolidation Flashcards

Question

Q: How does arousal influence synaptic memory consolidation?

Answer 1

Emotional or arousing experiences enhance memory consolidation via amygdala–hippocampus interactions. McGaugh et al. (2000) showed that administering norepinephrine or glucocorticoids into the basolateral amygdala after learning enhances memory for that event. Conversely, blocking amygdala activity or stress hormones impairs long-term retention, demonstrating that modulatory input from emotional circuits influences plasticity in memory-related regions like the hippocampus.

Answer 2

Classic experiments using anisomycin (a protein synthesis inhibitor) show that when injected into the brain after learning, animals fail to retain the memory. Short-term memory (STM) is spared, but long-term memory (LTM) is impaired. There’s a critical window (~1–4 hours post-training) during which new protein synthesis is necessary to stabilise memory. This supports the idea that memory requires the synthesis of plasticity-related proteins (PRPs) that strengthen synaptic connections.

Answer 3

CREB (cAMP response element-binding protein) is a key transcription factor activated by learning. Mice with impaired CREB function show deficient LTM. CREB overexpression leads to enhanced memory and increased engram allocation. Immediate early genes (IEGs) such as zif268, c-Fos, Arc are rapidly upregulated in neurons after learning and act as markers of plasticity. Epigenetic regulation (e.g., histone acetylation) enhances gene transcription during consolidation. HDAC inhibitors (which increase acetylation) enhance LTM in rodents, showing a role for chromatin remodelling in memory.

Answer 4

Engram cells are specific neurons activated during learning and reactivated during recall. Identified by expression of IEGs (e.g., c-Fos) or using transgenic systems (e.g., TetTag, c-Fos–tTA mice). Liu et al. (2012) used optogenetics to activate engram cells in the dentate gyrus → artificially induced a memory in a neutral context. Ablating or silencing engram cells prevents memory retrieval. Shows that specific neurons encode specific memories, and their reactivation is sufficient for recall.

Answer 5

Neurons with higher excitability during learning are more likely to be allocated to engrams. CREB overexpression in certain neurons biases those neurons toward memory storage. If two experiences occur within a short time window (e.g., 6 hours), they can be encoded by overlapping engram populations. Cai et al. (2016): Mice formed overlapping engrams for two events learned close in time → led to linked recall, where recalling one memory triggered another. This has implications for contextual associations and generalisation.

Answer 6

Mizuno et al. (2006) showed that male and female mice use different molecular pathways to support memory. Male mice require BDNF–TrkB signalling in the hippocampus for consolidation, but females use alternative pathways. Disruption of male-specific BDNF impairs memory only in males. Highlights the importance of sex as a biological variable in memory research and suggests different vulnerabilities or resilience to memory-related disorders.

Answer 7

Standard Model (Squire): Memory is initially dependent on the hippocampus, but with time it becomes hippocampus-independent as it's transferred to cortex. Supported by retrograde amnesia studies (older memories spared after hippocampal damage). Multiple Trace Theory (MTT): Proposes that episodic memories always depend on the hippocampus. Semantic memories may become hippocampus-independent. Goshen et al. (2011): Optogenetic inactivation of CA1 impairs remote memory recall, supporting MTT.

Answer 8

Reconsolidation is the process where a reactivated memory becomes labile and must be restabilised. Nader et al. (2000): Injected anisomycin into the amygdala after reactivating a fear memory → the memory was erased. Shows that retrieval triggers a new window of plasticity, requiring protein synthesis, similar to initial consolidation. Allows for updating, strengthening, or disrupting stored memories.

Answer 9

After a memory is retrieved, it becomes labile and must undergo reconsolidation to be stored again. Reconsolidation requires two key steps: Protein degradation (via the ubiquitin–proteasome system) to destabilise the original memory trace. New protein synthesis to restabilise and update the memory. Lee et al. (2008) showed that blocking proteasome activity after retrieval prevents destabilisation, meaning the memory cannot be modified — even if protein synthesis is blocked. Nader et al. (2000) demonstrated that blocking protein synthesis post-retrieval erases the memory. Key molecules involved: UPS (ubiquitin–proteasome system) Zif268 (critical for reconsolidation) Arc, CREB, and AMPAR subunits (e.g., GluA2) Conclusion: Reconsolidation is a two-phase process: first destabilisation via protein degradation, then restabilisation via synthesis. This allows memories to be updated or erased after retrieval.

Answer 10

Although both require protein synthesis, consolidation and reconsolidation rely on different genes and proteins. Lee et al. (2004) used antisense oligonucleotides in mice to knock down: BDNF: required for consolidation (long-term memory formation), but not reconsolidation. Zif268 (Egr1): required for reconsolidation, but not consolidation. These dissociable requirements suggest that reconsolidation is not just a repetition of consolidation, but a distinct and adaptive mechanism. Implication: Memories can be selectively updated after retrieval without affecting new memory formation.

Answer 11

Because memories become labile after retrieval, reconsolidation allows modification of maladaptive memories. Key therapeutic strategies: Propranolol after recall: In PTSD patients, propranolol (β-blocker) given post-recall reduces emotional intensity of the traumatic memory. (Brunet et al., 2008) Extinction during reconsolidation window: In rats, fear extinction training given shortly after memory reactivation led to long-lasting fear reduction. (Monfils et al., 2009) Pharmacological disruption: Experimental use of protein synthesis inhibitors post-reactivation erases memory in animals. Reconsolidation-based methods show promise for PTSD, phobias, and addiction by targeting and altering specific memory traces.