PSC 137 midterm 3

Amygdala and Emotional Learning

1. The Amygdala and Emotional Learning

• The amygdala is a subcortical structure located near the hippocampus in the medial temporal lobe.

• It is crucial for learning about danger and forming fear memories.

• It was historically considered the "fear center," but it also plays a role in processing positive emotional experiences.

• The amygdala communicates extensively with the hippocampus, which encodes contextual memory.

The Controversy Over "Fear" Terminology

• Some researchers avoid using the term "fear" in animal studies, as it's unclear whether animals consciously experience fear as humans do.

• Alternative terms: "Threat learning" or "Defensive behavioral system."

• However, some argue that if terms like "hunger" and "thirst" are used for animals, "fear" should be acceptable as long as it's clearly defined.

2. The Defensive Behavioral System

• A biological system evolved to help animals avoid and escape danger.

• Organizes behaviors such as:

  • Freezing (staying still to avoid detection)

  • Flight (running away)

  • Fight (attacking the threat)

  • Analgesia (reducing pain during a fight)

  • Autonomic arousal (increased heart rate and blood pressure)

• The amygdala is critical for organizing these responses, especially in learned fear situations.

3. Fear and Defensive Behavior Organization: The Predatory Imminence Theory

• Proposed by Michael Fanselow at UCLA.

• Defensive behaviors change systematically based on how imminent a threat is:

  1. No Threat → The animal engages in normal activities like grooming and foraging.

  2. Potential Threat (Pre-Encounter Stage) → The animal modifies its behavior (e.g., stops eating, seeks shelter, stays near walls).

  3. Detected Threat (Post-Encounter Stage) → The animal freezes or flees if possible.

  4. Predator Attack (Circa-Strike Stage) → The animal fights back violently (circus strike behavior) to escape.

  5. Predation (System Failure) → The animal is caught.

• This system applies to rodents, reptiles, and even humans in unexpected threats (e.g., jump-scares in haunted houses).

4. Experimental Studies on Fear Responses

(A) Looming Disk Study: Fear Responses to a Simulated Predator

• Method:

  • Mice were placed in a box with a screen on the ceiling.

  • A black disk suddenly expanded on the screen, simulating a predatory bird diving.

  • Researchers observed the mice's defensive reactions.

• Findings:

  • Some mice froze completely, staying still to avoid detection.

  • Others ran to shelter, demonstrating a flight response.

  • Showed that fear responses are automatic and hardwired.

(B) Snake and Mouse Study: Freezing & Circa-Strike Behavior

• Method:

  • A mouse was placed near a predatory snake.

  • The mouse initially froze completely, relying on stillness to avoid detection.

  • When the snake struck, the mouse immediately switched to wild, erratic movements (circus strike behavior) to escape.

• Findings:

  • Freezing is a common and effective survival strategy in prey animals.

  • Circa-strike behavior is a last-resort survival mechanism.

(C) Planet Earth’s Iguana Escape: Wild Example of Predatory Imminence Theory

• Video from Planet Earth:

  • A young iguana on a beach stays completely still (freezing) as snakes approach.

  • When one lunges, the lizard sprints at full speed, dodging multiple attacks.

  • Demonstrates the transition from freezing to flight as a defense mechanism.

5. The Role of the Amygdala in Defensive Behaviors

• The amygdala plays a crucial role in generating fear responses.

• If the amygdala is damaged, defensive behaviors disappear.

(A) Robogator Study: How the Amygdala Controls Fear Responses

• Researcher: Gene Tok, University of Washington.

• Robogator: A robotic alligator built with LEGO Mindstorm that moved toward rats.

• Study Setup:

  • Rats were trained to forage for food in an arena.

  • On Day 1, they freely retrieved food.

  • On Day 2, Robogator moved toward them, simulating a predator.

  • Normal rats immediately fled to safety when Robogator approached.

• Amygdala-Lesioned Rats:

  • A second group had their amygdala surgically removed.

  • These rats did not show fear—they casually walked past Robogator, unbothered.

  • Conclusion: Without the amygdala, innate fear responses disappear.

6. The Amygdala in Humans

• In rare cases, humans with amygdala damage (e.g., Urbach-Wiethe disease) also show impaired fear responses.

• Example:

  • A woman with bilateral amygdala damage repeatedly walked into dangerous neighborhoods and was mugged multiple times—yet never learned to avoid danger.

  • Demonstrates that the amygdala is necessary for recognizing threats and avoiding harm.

7. Neuroanatomy of the Amygdala

• Located near the hippocampus but has distinct functions.

• The amygdala consists of three major nuclei:

  1. Lateral nucleus – Receives sensory input about threats.

  2. Basal nucleus – Processes emotional significance of threats.

  3. Central nucleus – Sends signals to midbrain structures to initiate freezing, autonomic arousal, and analgesia.

• The amygdala is not just for fear—it attaches emotional significance to both positive and negative experiences.

Key Takeaways

1. The amygdala is central to fear learning and defensive behaviors.

2. Predatory imminence theory explains how animals adjust their responses based on threat proximity.

3. Experimental studies show how innate and learned fear responses are organized.

4. Lesion studies demonstrate that without the amygdala, defensive behaviors disappear.

5. Similar fear circuits exist in humans, affecting how we respond to danger.

This lecture laid the foundation for understanding how fear learning and emotional processing occur in the brain, setting the stage for future discussions on fear conditioning and threat memory formation.

Effects of amygdala lesions on learned fear

PAVLOVIAN (Classical) fear conditioning in rodents. 

1. The Role of the Amygdala in Fear Conditioning

• Fear learning is studied using Pavlovian fear conditioning, where an animal learns to associate a neutral stimulus (e.g., a tone or environment) with an aversive stimulus (e.g., a foot shock).

• The amygdala plays a critical role in forming these fear associations and driving defensive behaviors like freezing.

2. The Experiment: Amygdala Lesions & Fear Memory

Step 1: Training (Fear Conditioning)

• Rats are placed in a chamber where they receive a foot shock paired with a tone.

• Over time, they learn to fear both:

  • The context (place) where the shock happened (context fear).

  • The tone that predicts the shock (tone fear).

Step 2: Amygdala Lesions

• After learning, the rats undergo surgical removal of the amygdala on both sides of the brain.

Step 3: Memory Test

• The rats are tested for fear responses one week later (new fear memory test).

• A separate group of rats is tested 16 months later (old fear memory test).

3. Results: Loss of Fear Memory After Amygdala Lesions

• Context Fear (Fear of the Environment)

  • In control rats (no lesion), they froze in fear when placed in the conditioning chamber.

  • In amygdala-lesioned rats, freezing was almost completely abolished, meaning they no longer associated the environment with danger.

  • Even if the fear memory was 16 months old (a lifetime for a rat), amygdala removal still erased the fear.

• Tone Fear (Fear of the Auditory Cue)

  • In control rats, they froze when hearing the tone, even in a safe environment.

  • In amygdala-lesioned rats, freezing to the tone was nearly eliminated, showing they forgot the learned association

4. Key Conclusion: Amygdala Stores Fear Memories Permanently

• Unlike the hippocampus, which is required for some memories early on but not later, the amygdala is always necessary for recalling learned fear.

• If the amygdala is removed, even lifelong fear memories disappear.

• This suggests fear memories are permanently stored in the amygdala and are not transferred elsewhere over time.

5. Neural Pathways for Fear Learning

• Lateral Amygdala (LA) → Encodes tone fear (receives auditory input).
  
  

• Basolateral Amygdala (BLA) → Encodes context fear (receives spatial info from the hippocampus).
  
  

• Central Amygdala (CeA) → Triggers fear responses (freezing, heart rate increase, etc.).
  
  

• If the amygdala is removed, these pathways are disrupted, preventing the recall of both old and new fear memories.

6. Additional Findings on Amygdala and Fear Learning

• Long-Term Potentiation (LTP) in the Amygdala:

  • Similar to the hippocampus, LTP in the amygdala strengthens fear learning.

  • Blocking NMDA receptors in the amygdala prevents fear learning.

  • Blocking protein synthesis prevents the formation of long-term fear memories.

• Stimulation of the Central Amygdala Triggers Fear:

  • Directly stimulating the central amygdala in rats induces freezing behavior.

  • In humans with epilepsy, stimulating the amygdala can evoke feelings of intense fear.

The Amygdala is Essential for Fear Learning & Memory

• Removing the amygdala after learning erases fear memories.

• Unlike hippocampal-dependent memories, fear memories remain in the amygdala for life.

• Amygdala circuits control how animals associate threats with environmental cues.

Memory Consolidation

1. What is Memory Consolidation?

• Definition: The process by which a short-term memory becomes stronger and long-lasting, allowing it to be stored as a long-term memory.

• Distinction Between Fields:

  • In behavioral neuroscience (animal research), consolidation is directly linked to protein synthesis.

  • In cognitive neuroscience, consolidation is usually described as the time it takes for a memory to stabilize but without specifying molecular mechanisms.

2. The Role of Protein Synthesis in Consolidation

• Short-term memories do not require new proteins to be synthesized.

• Long-term memories depend on protein synthesis, which strengthens synaptic connections.

• The process involves:

  • Post-translational modifications for short-term memory.

  • Transcription and translation (gene expression, protein synthesis) for long-term memory.

  • The activation of Creb (cAMP Response Element-Binding protein), a key transcription factor that helps create proteins needed for long-term memory.

3. Experimental Evidence on Memory Consolidation

• Blocking Protein Synthesis Impairs Long-Term Memory
  

  • Scientists use protein synthesis inhibitors (e.g., anisomycin) to block memory formation.

  • If administered immediately after learning, the drug prevents long-term memory formation while leaving short-term memory intact.

  • If given 3-6 hours later, it has no effect, meaning memory formation is already complete.

• Creb Knockout Studies

  • Mice without Creb function can form short-term memories but fail to form long-term memories.

  • If Creb is restored (e.g., injected into the amygdala), long-term memory is rescued.

• Amygdala & Hippocampus Dependence

  • Amygdala is required for fear memories.

  • Hippocampus is needed for contextual memories.

  • Both structures show increased Creb activation after learning, indicating protein synthesis is taking place.

4. Time-Sensitivity of Memory Consolidation

• Protein synthesis must occur shortly after learning (within 1-3 hours).

• If protein synthesis is blocked right after learning, long-term memory is erased.

• If protein synthesis is blocked later (after 6+ hours), the memory remains intact.

• This suggests a critical window where memory formation is still flexible before it becomes permanently stored.

5. The Relationship Between LTP and Memory Consolidation

• LTP (Long-Term Potentiation) and Memory Formation are Similar

  • Short-term LTP lasts only an hour or so (similar to short-term memory).

  • Long-lasting LTP (L-LTP) requires protein synthesis (just like long-term memory).

  • Blocking Creb or protein synthesis disrupts both L-LTP and long-term memory.

    • Experiment: Researchers used a CREB antisense technique (which prevents CREB production) before training.

    • Findings:

      • Animals failed to form L-LTP, showing a lack of synaptic strengthening.

      • These animals also showed impairments in long-term memory, indicating that L-LTP and LTM share molecular mechanisms.

      • Conclusion: CREB is necessary for both L-LTP and long-term memory formation because it initiates the gene expression required for stable synaptic changes.

6. Real-Life Application: Emotional & Traumatic Memory Formation

• Fear memories (such as encountering a bear) go through the same process.

• If a fear memory is strong, it is quickly consolidated and stored permanently.

• This explains why traumatic memories can be difficult to forget, as they undergo rapid and intense consolidation.

7. Upcoming Discussion: Reconsolidation (Challenging Traditional Views)

• Traditional view: Once a memory is consolidated, it is permanent.

• Reconsolidation Hypothesis: Suggests that memories can become unstable again when recalled and can be altered or even erased.

• This discovery has major implications for treating PTSD and modifying traumatic memories.

Key Takeaways

✔ Memory consolidation turns short-term memories into stable long-term memories.
✔ Protein synthesis (via Creb and gene expression) is essential for consolidation.
✔ Blocking protein synthesis after learning prevents long-term memory formation but does not affect short-term memory.
✔ Consolidation is time-sensitive—there’s a critical period where memories are vulnerable before becoming stable.
✔ Upcoming research on reconsolidation suggests memories might not be as permanent as previously thought.

Fear Conditioning Circuit

Memory Reconsolidation

1. Reconsolidation: A Challenge to Traditional Memory Theory

• Previously, the field believed that once a memory was consolidated (after ~24 hours), it was stable and resistant to disruption.

• The key question that challenged this idea: What happens when a consolidated memory is retrieved?

2. The Key Experiment by Nader et al.

A. Standard Consolidation Test

• Rats underwent auditory fear conditioning (tone + shock).

• 24 hours later, anisomycin (a protein synthesis blocker) was infused into the amygdala.

• When memory was tested another 24 hours later, blocking protein synthesis had no effect—the fear memory remained intact.

• Conclusion: Once a memory is consolidated, it is stable and resistant to disruption.

B. The Reconsolidation Experiment

• Key difference: Before infusing anisomycin, the rats were given a brief tone test (retrieving the memory).

• After memory retrieval, anisomycin was infused to block protein synthesis.

• Result: The memory was completely disrupted—rats no longer froze in response to the tone.

• Key finding: Retrieving a memory reactivates consolidation, requiring new protein synthesis to stabilize it again. If protein synthesis is blocked after retrieval, the memory is lost.

• This phenomenon was named "Reconsolidation."3. Reconsolidation Follows the Same Rules as Consolidation

  • Memory is not immediately lost after retrieval, just like in standard consolidation.

  • If tested 1 hour after retrieval, the memory is still intact (short-term memory remains).

  • If tested 24 hours later, the memory is gone (long-term memory requires protein synthesis).

  • Implication: Retrieving a memory destabilizes it, and it must go through a new consolidation process to persist.

  4. Reconsolidation is Selective

  • Is reconsolidation specific to just the retrieved memory or does it affect all memories?

  • Experiment:

    • Rats were trained to fear two stimuli: a tone (CS1) and a light (CS2).

    • Only CS1 (tone) was reactivated before protein synthesis was blocked.

    • Result: Memory for CS1 (retrieved memory) was impaired, but memory for CS2 (non-retrieved memory) was intact.

  • Conclusion: Reconsolidation only affects the memory that was retrieved. Other memories remain stable.

  5. Reconsolidation in the Hippocampus

  • Fear memories in the amygdala undergo reconsolidation. Does this also happen for hippocampus-dependent memories?

  • Experiment:

    • Rats underwent contextual fear conditioning, which depends on the hippocampus.

    • 24 hours later, protein synthesis was blocked in the hippocampus without retrieval → No effect on memory.

    • However, if the memory was retrieved before blocking protein synthesis, long-term memory was impaired.

  • Conclusion: Reconsolidation also occurs in the hippocampus, not just the amygdala.

  6. Why Does the Brain Reconsolidate Memories?

  • If a memory is already consolidated, why would retrieving it make it unstable?

  • Nader’s Hypothesis:

    • When a memory is retrieved, the connections (synapses) between neurons weaken.

    • To remain stable, the memory must undergo protein degradation followed by new protein synthesis.

    • If protein synthesis is blocked after retrieval, the memory cannot be stabilized and is lost.

  • Possible Reason:

    • The brain might use reconsolidation to update memories—adapting stored information based on new experiences.

  7. Experimental Evidence: Blocking Protein Degradation Prevents Memory Loss

  • If protein degradation happens first, then new proteins must be made to restore memory.

  • New Experiment:

    • Used a drug to prevent protein degradation.

    • Then blocked protein synthesis.

    • Result: Memory remained intact.

  • Conclusion: Memory reconsolidation involves a two-step process:

    1. Memory retrieval leads to protein degradation (destabilization).

    2. New protein synthesis is required to restabilize it.

    • If degradation is blocked, memory remains intact even if protein synthesis is stopped.

  8. Implications of Reconsolidation Theory

  • Memories are not fixed—retrieving them makes them malleable.

  • Could be a mechanism for memory updating—allowing us to integrate new information into old memories.

  • Has potential applications for treating PTSD, phobias, and false memories—by disrupting harmful memories through targeted retrieval + protein synthesis inhibition.

  Key Takeaways

  ✔ Memories are not permanently "etched" into the brain—they can be modified when retrieved.
  ✔ Retrieving a memory makes it vulnerable, requiring reconsolidation (new protein synthesis) to stabilize it again.
  ✔ Reconsolidation happens in both the amygdala (fear memories) and hippocampus (contextual memories).
  ✔ Memory reconsolidation can be selectively targeted to disrupt or modify specific memories.
  ✔ Blocking protein degradation prevents memory destabilization, showing that reconsolidation requires old protein breakdown before new proteins are synthesized.
  ✔ This research challenges the traditional view that consolidated memories are permanent.

Fate of Retrieved Memories

1. Reconsolidation: The Reprocessing of Retrieved Memories

• Reconsolidation is a phenomenon first described by Karim Nader and Joe LeDoux while studying fear memory formation in the amygdala.

• It was previously believed that once a memory was consolidated (~24 hours after learning), it was permanently stable and resistant to disruption.

• However, Nader's experiments showed that retrieving a memory makes it malleable again, requiring new protein synthesis to stabilize it.

• If protein synthesis is blocked after retrieval, the memory becomes unstable and can be lost.

Key Experiment by Nader et al.:

1. Fear conditioning in rats (tone + shock).

2. 24 hours later, they retrieved the memory by playing the tone (without a shock).

3. After retrieval, anisomycin (a protein synthesis blocker) was infused into the amygdala.

4. Result: The memory was lost—rats no longer froze to the tone the next day.

5. Conclusion: Retrieved memories must undergo reconsolidation (another round of protein synthesis) to remain stable.

Active Trace Theory

• Memories in an "active state" are vulnerable to disruption.

• Two ways a memory becomes active:

  1. A novel experience (new memory formation).

  2. Retrieving a long-term memory makes it active again.

• This explains why blocking protein synthesis after retrieval disrupts memory.

2. Potential Applications of Reconsolidation: Erasing Unwanted Memories

• Reconsolidation studies suggest that even old, consolidated memories can be altered or erased.

• Implications for treating PTSD, addiction, and phobias.

Case Study: Addiction and Drug-Associated Cues

• Problem: Why do drug cues trigger relapse?

  • Drug addiction is often reinforced by environmental cues (such as a place, a smell, or a sound) that were previously associated with drug use.

  • When an addicted person sees or hears these cues, it triggers a memory of drug use, which leads to intense craving and potential relapse.

  • Even after quitting, these strongly ingrained memories remain, making it difficult to stay sober.

  • Traditional treatments cannot erase these memories; they only help manage cravings.

• Can we use memory reconsolidation techniques to weaken or erase drug-related cues?

Experiment: Reward Circuity

Step 1: Creating the Addiction Model in Rats

1. Self-Administration Phase

   • Rats learned to press a lever to receive a direct cocaine injection into their brain.

   • Result: The rats became addicted, pressing the lever repeatedly to get more cocaine.

2. Conditioning Phase (Pairing Tone with Cocaine)

   • The lever was removed.

   • Every time a tone was played, the rat automatically received cocaine (without pressing anything).

   • Result: The tone became a strong drug cue, just like environmental cues in human addiction.

3. Extinction Phase (Simulating Abstinence)

   • The lever was placed back, but now pressing it did not deliver cocaine.

   • Initially, the rats kept pressing in hopes of getting the drug, but after a few days, they stopped.

   • This mimics real-world abstinence, where an addict stops using but still has strong cravings.

4. Relapse Test (Cue-Induced Craving)

   • The experimenters played the tone again.

   • Even though no cocaine was available, the rats immediately started pressing the lever again.

   • Why? The tone triggered a craving because it reactivated the drug memory.

💡 This phase represents a major challenge in addiction recovery: even after abstinence, encountering cues can trigger relapse.

Step 2: Disrupting the Drug Memory with Reconsolidation Blockers

• Researchers tested whether blocking protein synthesis after memory retrieval could erase the cocaine-tone association.

• They infused a drug called Zif268 antisense (which blocks protein synthesis) into the nucleus accumbens (the brain's reward center).

• The idea was to prevent reconsolidation of the drug memory immediately after it was retrieved.

Step 3: Testing if the Memory Was Weakened

1. 24 hours later, the rats were brought back.

2. The tone was played again while the lever was available.

3. Results:

   • Control group (no drug infusion) → Rats pressed the lever a lot (strong craving response).

   • Rats that received the protein synthesis blocker (Zif268 antisense) → Pressed the lever significantly less.

   • Conclusion: The drug-associated memory was weakened—the tone no longer triggered intense craving.

Key Findings

✔ Blocking reconsolidation erased the drug-cue memory.
✔ Rats exposed to the tone no longer showed strong drug-seeking behavior.
✔ This suggests a potential method to treat addiction in humans by weakening relapse triggers.

• Real-world applications: Clinical trials attempted to use reconsolidation procedures to treat addiction, but results in humans have been inconsistent.

3. Differences Between Consolidation and Reconsolidation

• Do consolidation and reconsolidation use the same cellular mechanisms?

  • Both require protein synthesis, but involve different molecular pathways.

  • BNDF (Brain-Derived Neurotrophic Factor) is required for consolidation, but not for reconsolidation.

  • ZIP protein (Zif268) is required for reconsolidation, but not for consolidation.

• Implication: Reconsolidation is not just a repetition of consolidation—it serves a distinct function.

4. Functions of Reconsolidation: Strengthening vs. Updating Memory

1. Strengthening - memories become stronger and longer lasting each time they’re retrieved.

2. Updating - new information can be intergrated into previously formed memories.

3. Experiment:

   • Experiment 1: Does Reconsolidation Strengthen Memory?

     1. Two-Day Training Protocol:

        • On Day 1, mice were trained with a context-shock pairing to form a fear memory.

        • On Day 2, they were re-exposed to the context and received another training trial (another shock).

        • This second trial reactivates the memory, triggering reconsolidation.

     2. Protein Manipulation:

        • Zif268 antisense (blocks Zif protein, important for reconsolidation) and BDNF antisense (blocks BDNF protein, important for consolidation) were used to determine their roles.

        • Results: Blocking Zif268 impaired memory, but blocking BDNF had no effect.

        • Conclusion: Reconsolidation (not consolidation) was engaged when an existing memory was reactivated and strengthened.

   • Experiment 2: What Happens When Both Training Trials Are Given in One Session?

     1. Instead of spreading training over two days, researchers compressed both learning trials into a single session.

     2. Since the memory had not yet been consolidated, the expectation was that only consolidation, not reconsolidation, would occur.

     3. Results:

        • Blocking BDNF impaired memory, but blocking Zif268 had no effect.

        • Conclusion: When both learning trials happened close together, only consolidation was required, not reconsolidation.

     4. Experiment 3: Does Reconsolidation Help Update Memory with New Information?

     1. New Context Design:

        • Day 1: Mice learned a fear memory in Context A.

        • Day 2: They were trained in a completely different Context B.

        • Since Context B was new, this learning event should not engage reconsolidation of the old memory but instead form a new memory via consolidation.

     2. Protein Manipulation:

        • BDNF antisense impaired learning in Context B.

        • Zif268 antisense had no effect.

        • Conclusion: The new learning event in a different context engaged consolidation, not reconsolidation, supporting the idea that reconsolidation is selective to the retrieved memory.

     Experiment 4: Is Protein Degradation Required for Memory Strengthening?

     1. Researchers investigated whether preventing protein degradation would stop reconsolidation from strengthening a memory.

     2. Beta-lactone (B-lac) was used to prevent protein degradation before re-exposure to the memory.

     3. Results:

        • If protein degradation was blocked, the memory was still intact but could not be strengthened.

        • Conclusion: Reconsolidation involves breaking down old proteins before synthesizing new ones to strengthen or update the memory.

5. Systems Consolidation: Transferring Memories from the Hippocampus to the Cortex

• While recent memories rely on the hippocampus, over time, memories become stored in the neocortex.

• This process is called systems consolidation.

Types of Consolidation

• Example: When you first learn a new skill or fact, the hippocampus stores it. Over time, the memory moves to the neocortex for permanent storage.

6. Ribot’s Law & Temporal Memory Stability

• Older memories are more resistant to disruption than newer ones.

• Evidence from amnesia studies:

  • Patients with hippocampal damage struggle with recent memories but can recall older memories.

  • Electric shock experiments showed recent memories were disrupted, but older ones remained intact.

• Conclusion: older memories (remote) last longer

7. Experimental Evidence for Systems Consolidation

• Famous Faces Test (Larry Squire, UCSD):

  • Patients were tested on famous people from different decades.

  • After receiving electroconvulsive therapy (ECT), they forgot recent famous faces but remembered older ones.

  • Implication: Recent memories rely on the hippocampus, but older memories are stored in the neocortex.

Key Takeaways

✔ Memories are not permanent—they are reprocessed every time they are retrieved (reconsolidation).
✔ Blocking protein synthesis after retrieval can erase a memory.
✔ Reconsolidation serves two functions: strengthening and updating memories.
✔ Over time, memories transfer from the hippocampus to the neocortex (systems consolidation).
✔ Older memories are more resistant to disruption than newer ones (Ribot’s Law).