Learning and memory Flashcards
Who is HM and what we have found by studying him?
HM (Henry Molaison) was a patient who underwent bilateral medial temporal lobe resection (removal of amygdala, hippocampus, part of frontal cortex) to treat epilepsy. As a result, he developed severe anterograde amnesia, meaning he could not form new explicit memories, though his IQ and personality remained intact.
Key Findings from Studying HM:
1. Hippocampus is essential for forming new explicit (declarative) memories, but not for retrieving old ones.
2. Short-term and working memory were preserved, but long-term explicit memory formation was impaired.
3. Implicit memory (procedural learning) was intact – shown through tasks like mirror tracing, where he improved over time despite having no recollection of practicing.
4. Memory is not a single process – different brain structures support different types of memory (e.g., hippocampus for declarative memory, basal ganglia for procedural memory).
HM’s case revolutionized our understanding of memory systems and brain function.
What kind of memory tests HM fail to do well?
HM failed in tests that required explicit (declarative) memory, particularly those involving new learning and recall. Some key tests he struggled with include:
1. Recognition and Recall Tests
* Given a list of words or images to study, he performed poorly when asked to recall them later. (Can’t even remember receiving the list)
* Paired-association tasks: He could not learn and remember word pairs.
2. Digit Span +1 Task
* He could repeat a short sequence of numbers but difficult to solve problem once the sequence exceeded e.g., 7±2, showing limited short-term to long-term memory transfer.
What’s priming tasks and perceptual identification task, and what have found by studying wit HM
Priming Tasks & Perceptual Identification Task
1. Priming Tasks
* Involves exposure to a stimulus that influences a later response without conscious awareness.
* Example: Word Stem Completion – HM was given a list of words to study, then later shown word fragments (e.g., “app___”) and asked to complete them.
* Finding: HM was more likely to complete the words with those he had seen earlier, despite having no recollection of seeing them before.
2. Perceptual Identification Task
* Involves showing words/images very briefly (hard to consciously perceive) and asking participants to identify them.
* Finding: HM was better at identifying words/images he had seen earlier, even though he had no memory of studying them.
Key Conclusion from HM’s Performance
* Priming and perceptual learning rely on implicit memory, which does not require the hippocampus.
* HM’s intact priming ability suggests that implicit memory is supported by different brain structures (e.g., neocortex) rather than the medial temporal lobe.
What’s mirror tracing task and what’s been found in HM’s study?
Mirror Tracing Task
* A procedural learning task where participants trace a shape while only viewing their hand through a mirror, making coordination more difficult.
* It measures motor learning and implicit memory.
Findings in HM’s Study
* HM improved across trials, making fewer errors each day.
* Despite his improvement, he had no memory of ever doing the task before.
* This demonstrated that procedural memory (motor learning) was intact, even though declarative memory (explicit recall of learning) was impaired.
Key Conclusion
* The hippocampus is not necessary for procedural memory. Instead, the basal ganglia and cerebellum play a major role in motor learning.
* Memory is not a single system—declarative and procedural memory rely on different brain structures.
What is declarative and non declarative memory?
- Declarative (Explicit) – Conscious recall of facts/events (Hippocampus).
- Episodic – Personal experiences (“I had coffee this morning”).
- Semantic – General knowledge (“Paris is the capital of France”).
- Non-Declarative (Implicit) – Unconscious learning, influences behavior (Basal Ganglia, Cerebellum).
- Procedural – Skills/habits (riding a bike, mirror tracing).
- Priming – Prior exposure affects response (word stem completion).
- Classical Conditioning – Associative learning (fear conditioning).
- Non-Associative – Habituation & sensitization.
Key Difference – Declarative requires conscious recall, Non-Declarative is automatic.
HM’s Case – Lost declarative memory but retained non-declarative memory (e.g., improved at mirror tracing but had no memory of learning it).
What’s the familiarity we can found in HM’s test of learning.
- Test – HM was shown images he had seen before and asked to choose between a familiar and unfamiliar one (two-alternative forced choice task).
- Finding – He performed well, often selecting the previously seen image, despite having no recollection of seeing them before.
Key Conclusion – Familiarity-based recognition can occur without explicit recall, suggesting some forms of recognition memory do not depend on the hippocampus.
What’s the tests of association (classical conditioning paradigms) HM took and what’s found
- Test – HM was exposed to neutral stimuli (e.g., a tone) paired with an unconditioned stimulus (e.g., a puff of air to the eye) that naturally elicited a blink reflex.
- Finding – He successfully acquired conditioned responses, blinking in response to the tone alone after repeated pairings.
Key Conclusion – Classical conditioning does not require the hippocampus; instead, cerebellar circuits support this form of learning.
HM could be classical conditioned even tho he do not realize he had been exposed to the tone.
What’s the other two similar but difference cases to HM, N.A and Clive wearing. What’s the impairment and what’s the influence.
Case of Patient N.A.
* Cause – A fencing accident that resulted in damage to the dorsomedial thalamus（背内侧丘脑） and mammillary bodies（乳头体）, which are part of the medial diencephalon（间脑内侧区）.
* Impairment – Severe anterograde amnesia, especially for declarative memory, but with intact procedural memory.
* Preserved Abilities – Could still learn new motor skills and had normal intelligence and working memory, similar to HM, but with less severe retrograde amnesia.
Key Influence on Memory Research
* Showed that memory formation is not solely dependent on the hippocampus, as damage to the medial diencephalon also leads to anterograde amnesia.
* Reinforced the idea that the hippocampus and diencephalon form a connected network essential for encoding new declarative memories.
* Demonstrated that non-declarative memory (e.g., motor learning) does not rely on the hippocampus or diencephalon, similar to findings from HM.
* Clive Wearing * Impairment – Profound anterograde and retrograde amnesia due to herpes simplex encephalitis (脑炎), unable to form new memories and lost most past memories. * Influence – Demonstrated severe disruption of declarative memory, but procedural memory (e.g., playing the piano) remained intact, reinforcing the distinction between explicit and implicit memory systems.
What‘s the case of Patient K.C.
Case of Patient K.C.
* Cause – A motorcycle accident that caused extensive brain damage, including the hippocampus（海马体）, parahippocampal cortex（旁海马皮层）, and frontal cortex（额叶皮层）.
* Impairment – Severe episodic memory loss, unable to recall personal past experiences (retrograde amnesia), and anterograde amnesia, unable to form new explicit memories.
* Preserved Abilities – Semantic memory remained intact (e.g., he could recall factual knowledge but not personal events), could converse normally, and still retained procedural skills like playing chess, despite not remembering how he learned them.
Key Influence on Memory Research
* Provided strong evidence that episodic and semantic memory are dissociable, meaning personal experiences and factual knowledge rely on different brain mechanisms.
* Confirmed that the hippocampus is critical for forming and retrieving episodic memories but is not necessary for semantic or procedural memory.
Key Conclusion – Patient K.C.’s case demonstrated that episodic memory requires the hippocampus, while semantic and procedural memory can be preserved despite severe hippocampal and cortical damage.
What can we learn about long-term memory from case study of HM, K.C, etc.
- Memory is not a single system – Different types of long-term memory rely on distinct brain structures.
- Hippocampus is essential for declarative memory – HM and K.C. showed that hippocampal damage leads to anterograde amnesia, preventing the formation of new explicit memories.
- Episodic and semantic memory are dissociable – K.C. lost episodic memory but retained semantic knowledge, proving that personal experiences and general facts are stored differently.
- Procedural memory is independent of the hippocampus – HM and K.C. could still learn motor skills (e.g., mirror tracing, chess), showing that the basal ganglia and cerebellum support procedural memory.
Key Conclusion – Long-term memory consists of multiple subsystems (episodic, semantic, procedural), supported by different neural structures rather than a single memory center.
Why are some memory conscious and some not
- Declarative Memory (Conscious) – Requires active recall and awareness, supported by the hippocampus and medial temporal lobe.
- Episodic Memory – Remembering personal experiences (e.g., “I went to a concert last year”).
- Semantic Memory – Storing facts and general knowledge (e.g., “Paris is the capital of France”).
- Non-Declarative Memory (Unconscious) – Does not require awareness and influences behavior automatically, relying on structures like the basal ganglia, cerebellum, and neocortex.
- Procedural Memory – Skills and habits (e.g., riding a bike, playing chess).
- Priming – Exposure to stimuli influences responses without conscious effort.
- Classical Conditioning – Associative learning (e.g., blinking to a tone after pairing with an air puff).
Key Conclusion – Conscious memory (declarative) depends on the hippocampus, while unconscious memory (non-declarative) relies on subcortical structures, allowing us to perform complex behaviors without deliberate thought.
What’s the Proposed information flow.
- Information Flow – Sensory information flows from association cortices（联想皮层） into the parahippocampal cortex（旁海马皮层） and perirhinal cortex（梨状皮层）, then converges in the entorhinal cortex（内嗅皮层）, the main gateway to the hippocampus（海马体）.
- Convergence in the Hippocampus – The entorhinal cortex（内嗅皮层） sends information to the dentate gyrus（齿状回）, which then projects to CA3 region（CA3区） and subsequently to CA1 region（CA1区）, where different inputs are integrated into a coherent memory representation.
- “Highway of Memory” – The fornix（穹窿） serves as the primary output pathway of the hippocampus, transmitting processed memory information to the mammillary bodies（乳头体） and anterior thalamus（丘脑前部）, which further contribute to memory consolidation and distribution.
Key Conclusion – The hippocampus（海马体） functions as a memory integration hub, organizing and encoding information before relaying it through the fornix（穹窿） to other brain regions for long-term storage and retrieval.
What’s the different contributions to declarative memory?
Most declarative memory for facts and events consists of two components: the sense of familiarity with the features of the item (“I’ve seen that actress somewhere…”), and additionally recollection of the item in the specific context in which it was presented (“Oh, she played Daenerys in Game of Thrones”).
Perirhinal cortex is thought to be responsible for the sense of familiarity in memory, whereas recollection of the item is the function of the hippocampus. Processing of contextual aspects of memory (including spatial cognition, which we will discuss in more detail a little later) appears to depend especially on the parahippocampal cortex
In general, the performance of experimental animals suggests that the hippocampus acts as the final stage of convergence for adjacent regions of cortex.
In keeping with this schema, people with specific hippocampal damage appear to have difficulties with recollection, while familiarity-based aspects of memory are spared. Conversely, people with surgical lesions that include the perirhinal cortex but not the hippocampus experience impaired familiarity with stimuli despite preserved recollection. The medial temporal lobe is not the only brain region required to form new declarative memories (amygdala can enhance familiarity in memory test).
What’s the definition of learning and memory
Learning is the process of acquiring new information.
Memory is the ability to store and retrieve information. The specific information stored in the brain.
where is hippocampus?
Hippocampus
* Interior medial aspect of the
temporal lobe
* Extends into a structure called
the fornix (connects to the
mammillary body
* Latin for seahorse
Path way: receive LEC and MEC inputs, -> dentate gyrus -> CA 3 -> CA 1.
What is the associational/convergence hierarchy to hippocampus?
Ventral Stream（腹侧通路） → LEC（侧内嗅皮层） – Processes “what” information, handling object recognition, features, and non-spatial context.
Dorsal Stream（背侧通路） → MEC（内侧内嗅皮层） – Processes “where” information, supporting spatial navigation, movement tracking, and environmental mapping.
Hippocampus（海马体） as the Integration Center
Combines object (LEC) and spatial (MEC) information into a unified episodic memory.
Key Takeaways - The ventral stream identifies objects, while the dorsal stream encodes spatial locations before reaching the hippocampus.
This dual-stream system enables episodic memory formation, linking what happened and where it happened.
Key Difference – LEC focuses on what is in the environment (objects and context), while MEC focuses on where things are (spatial positioning and movement). Both feed into the hippocampus, where information is integrated for episodic memory formation.
What’s the goal of open field observation?
Open Field Observation: Purpose and Process
Open field observation is a behavioral experiment designed to study how neurons in the hippocampus and entorhinal cortex respond to spatial exploration. The goal is to identify and define receptive fields for neurons involved in navigation and memory processing.
How It Works:
* An animal (typically a rat or mouse) is placed in an open, unmarked arena and allowed to freely explore.
* Neural activity is recorded to analyze how different brain regions encode spatial and contextual information.
* Researchers aim to identify place cells（位置细胞）in the hippocampus, which fire when the animal is in a specific location.
* They also look for grid cells（网格细胞）in the medial entorhinal cortex（MEC, 内侧内嗅皮层）, which fire in a regular grid-like pattern, forming a spatial coordinate system.
* Understand how spatial and non-spatial information is processed in the hippocampal network.
Key Takeaway
Open field observation helps researchers understand how the brain encodes space and movement, revealing the neural basis of navigation, memory, and spatial representation.
What’s place cells and grid cells and what could they tell us?
Place Cells & Grid Cells: What They Are and What They Tell Us
Place Cells（位置细胞）
* Found in the hippocampus（海马体）, these neurons fire when an animal is in a specific location within an environment.
* Each place cell is associated with a particular “place field”, meaning it becomes active only when the animal is in that specific area.
Grid Cells（网格细胞）
* Found in the medial entorhinal cortex（MEC, 内侧内嗅皮层）, these neurons fire in a hexagonal (六角) grid pattern across an environment.
* Unlike place cells, grid cells do not correspond to a single location but create a repeating, structured spatial map. Grid system keep tract space of where we have been and where we’re going. It knows the pattern from a -> b -> C, where’s place cell do not know that pattern.
What They Tell Us About the Brain
* Place cells represent specific locations, helping form a mental map of the environment.
* Grid cells provide a coordinate system, allowing for path integration and navigation.
* Together, they reveal that the hippocampus and entorhinal cortex work together to encode spatial memory, supporting navigation and episodic memory formation.
Key Takeaway – Place cells and grid cells are fundamental to understanding how the brain processes space, forms memories, and enables navigation.
What’s border cells?
Border Cells（边界细胞）
* Location – Found in the medial entorhinal cortex (MEC, 内侧内嗅皮层) and some hippocampal regions.
* Function – Fire when an animal is near a boundary, such as a wall or edge of an environment.
* Consistency – Their activity remains stable regardless of the size or shape of the environment, meaning if a new wall is added, a new border field forms in alignment with it.
Key Takeaway – Border cells help animals recognize and navigate within enclosed spaces, ensuring that memory representations include environmental boundaries.
What’s head direction cells
Head Direction Cells（头方向细胞）
* Location – Found in the medial entorhinal cortex (MEC, 内侧内嗅皮层), anterior thalamus (丘脑前部), and other navigation-related brain areas.
* Function – Fire when an animal’s head is facing a specific direction, regardless of location.
* Characteristics – Each cell has a preferred firing direction, similar to a compass, and remains active as long as the head maintains that orientation.
Key Takeaway – Head direction cells provide an internal sense of direction, helping animals maintain spatial orientation even in the absence of external cues.
What does open field studies reveal?
Open Field Studies – MEC contains grid cells (spatial coordinate system), border cells (detect boundaries), and head direction cells (track orientation).
Conclusion – MEC is crucial for space and movement-related firing.
Alzheimer’s Disease Impact – MEC is one of the first affected regions, leading to spatial memory deficits, getting lost in familiar places, and difficulty with complex navigation tasks.
Future Research – How adding objects to the open field affects spatial representation.
What’s object cells and trace cells?
Object Cells & Trace Cells
* Object Cells（物体细胞） – Found in the lateral entorhinal cortex (LEC, 侧内嗅皮层), these neurons fire when an object is present in a specific location. Some object cells respond to specific objects, while others track new vs. familiar objects. They help link objects to experiences, supporting episodic memory.
* Trace Cells（痕迹细胞） – A subtype of object cells in the LEC that continue to fire even after an object is removed. They help track where an object was, allowing the brain to maintain a temporal representation of objects, which is essential for memory formation and recall.
Key Difference – Object cells respond to the presence of objects, while trace cells keep firing even after the object is no longer there, maintaining a memory trace of its past location.
What’s lesion studies?
Two tasks tested how LEC (lateral entorhinal cortex) and MEC (medial entorhinal cortex) lesions affect object recognition vs. context recognition.
Task 1: Object Recognition
• Setup – Mice saw three objects over three trials. In the fourth trial, one object was replaced with a duck.
• Results
• Control Group – Increased exploration, indicating they noticed the object change.
• LEC Lesion – No increase, showing LEC is critical for object recognition.
• MEC Lesion – Slight increase, suggesting MEC plays a minor role.
• Takeaway – LEC is required for object recognition, while MEC has limited involvement.
Task 2: Context Recognition
• Setup – Instead of changing an object, the background was altered in the fourth trial.
• Results
• Control Group – Increased exploration, meaning they noticed the background change.
• LEC Lesion – Slight increase, suggesting LEC has some role in context processing.
• MEC Lesion – No increase, showing MEC is essential for recognizing background changes.
• Takeaway – MEC is required for context recognition, while LEC has minor involvement.
Overall Findings
• LEC (Lateral Entorhinal Cortex) → Object recognition (what changed).
• MEC (Medial Entorhinal Cortex) → Context recognition (background changed).
• Control mice detected both changes, confirming LEC’s role in object memory and MEC’s role in spatial/context memory.
what does the place field told us?
Place fields - the area in space that elicit firing in a place cell of the hippocampus
The hippocampus functions as a spatial map, and the hippocampus fires not only in a specific spot, but when something specific is happening in that spot. （老鼠看正前方时，侧方的direction cell 也在firing只是没有正前方的active，然后direction cell的input也没有place cell在hippocampus里fire的强）。
how is the brain interpreting the differences (different places/environment and the condition it has) when same cells are firing. (Global remapping, and rate remapping).
Global remapping occurs when place cells（位置细胞）in the hippocampus completely change their firing patterns in response to a new environment or context. This phenomenon provides key insights into how the brain encodes distinct experiences and environments.
Key Findings from Global Remapping
• Distinct Memory Representations – The hippocampus creates unique neural maps for different environments, preventing interference between memories.
• Context-Dependent Encoding – Changes in both spatial (location) and non-spatial (context, cues) factors can trigger remapping, showing that the hippocampus encodes more than just space.
• Supports Episodic Memory Formation – Since episodic memory requires distinguishing one experience from another, global remapping allows the brain to separate similar yet different experiences.
Key Conclusion - When the global environment changes, the pattern of firing also changes. So some neurons stop firing some neuron start firing. A specific pattern of firing a different combination of individual neurons represent different places.
What’s rate remapping.
Rate remapping occurs when non-spatial or less spatial stimuli (e.g., local cues, objects, or testing chamber conditions) change while the overall environment remains the same.
Key Characteristics:
Place cells（位置细胞）maintain their spatial firing fields, meaning they still fire in the same locations.
However, their firing rates change significantly (up to 10x), depending on the contextual or non-spatial modifications.
This firing rate variation within the same neuronal ensemble may serve as a mechanism for distinguishing different experiences that occur in the same place.
Key Conclusion:
Rate remapping allows the brain to encode different experiences within the same spatial location by adjusting neuronal firing intensity rather than altering the spatial map itself. (When local cues changed in the same global context, our brain can tell the differences by changing the rate of firing.)
what can we find in rate remapping + LEC legion.
LEC is responsible for influencing rate remapping, as local cues only influence hippocampal place cell firing rates when the LEC is intact.
Additionally, MEC is likely to be responsible for influencing global remapping.
In conclusion: MEC provide spatial coordinate system and the LEC provide the content. Adding them together creates a unique combination of firing neurons and a unique frequency of firing of neurons (A specific map created).
With the convergence of these input, hippocampus then could tell us the specific place and its experience.
What’s the relationship between stimuli and firing rate?
In higher level representations of information:
The relationship between stimuli and firing rate is unclear (because it depends on unique summation of a neurons inputs)
Thus distinct patterns (mental map) = distinct experiences.
What’s other stimulus human can use to form map?
The goals, thoughts in human’s mind are non spatial stimulus patterns. What you are thinking/feeling at a different time, these different aspect can get stored in the hippocampus in a general context of where they’re happening and when.
What’s the findings in Article: “Hippocampal Place-Cell Sequences Depict Future Paths to Remembered Goals”
This article investigates how hippocampal place cells（位置细胞）encode future paths toward remembered goals, revealing their role in goal-directed navigation.
Researchers said these are interneurons, that is small neurons that connect neurons in the same area
Key Findings from the Experiment
• Open Field Exploration – Rats were allowed to explore a large open field, with different home bases (D1 on Day 1, D2 on Day 2).
• Place Cells in CA1 Recorded – Custom electrodes recorded neural activity in hundreds of CA1 place cells, identifying their firing fields during movement.
• Place-Cell Sequences Predict Future Paths – Place cell activity not only represented the rat’s current location but also sequences of future movement, suggesting prospective coding in spatial memory.
Key Takeaway - We notice that the pattern of hippocampus represents a logical order that mouse plan go. Suggesting that the hippocampus does not just represent the present environment but also predicts upcoming movement toward goals, supporting its role in planning and memory-guided navigation.
What is trajactory events, and home/away condition.
Trajectory events occur when hippocampal place cells fire in sequences representing movement paths. These can be classified into home events and away events, based on their relation to the animal’s starting location (home base).
Key Types of Trajectory Events
Home Events – Occur near the home base, representing planned or recalled paths leading away from the starting position. Often associated with preplay (predicting upcoming movement).
Away Events – Occur far from the home base, often representing sequences of movement leading back to home. These are linked to replay (retracing previous paths).
Key Takeaway
Both home and away events suggest that the hippocampus encodes movement sequences bidirectionally, allowing for both future path planning (preplay) and past path recall (replay). we noticed that the pattern of hippocampus represents a logical order that mouse plan to go.
What’s the spatial water maze task, and what does it tells us?
• Also known as the Morris Water Maze (MWM), this task is used to study spatial learning and memory in rodents.
• The animal is placed in a circular pool of opaque water with a hidden submerged platform.
• Over repeated trials, the animal learns to use spatial cues around the room to navigate and find the platform efficiently.
What Does It Tell Us?
1. Hippocampus is Critical for Spatial Memory – Lesions in the hippocampus（海马体） severely impair the animal’s ability to learn and remember the platform’s location.
2. Role of Place Cells – Place cells（位置细胞） in the hippocampus fire in specific locations, forming a cognitive map for navigation.
3. Testing Spatial Learning & Memory Deficits – Used to study memory disorders like Alzheimer’s disease, where impaired navigation indicates early hippocampal dysfunction.
4. Probe Trials Confirm Memory Recall – When the platform is removed, a well-trained rat will spend more time searching in the correct quadrant, showing memory retention.
Key Takeaway
The spatial water maze demonstrates that the hippocampus is essential for spatial learning, and that animals use allocentric (external cue-based) navigation to encode and recall locations in space.
What’s the function of peritoneal cortex and how could it be responsible for whole representation of an observed object?
Perirhinal Cortex is also associated with the feeling of familiarity, so it particularly involved with perceptual priming.
Function of PRC (梨状皮层)
• Integrates sensory inputs (shape, texture, color) into a unified object representation.
• Distinguishes novel vs. familiar objects, supporting familiarity-based recognition.
• Links to hippocampus for object-context associations.
Why PRC Leads to Entorhinal Cortex (EC, 内嗅皮层)?
• PRC processes complex object features and sends integrated information to EC, which further relays it to the hippocampus for memory encoding.
• PRC-to-EC pathway allows objects to be linked with spatial and episodic memory.
Why Does Repeated Exposure Decrease Activity in PRC?
• Neural adaptation – Repeated stimuli require less processing, leading to reduced firing in the ventral stream (e.g., occipitotemporal cortex).
• Familiarity effect – PRC responds strongly to novel objects, but activity decreases once an object is recognized as familiar.
Key Takeaway
PRC binds object features into a whole representation, relays this to EC for memory processing, and reduces firing for familiar stimuli, optimizing recognition efficiency.
What’s the different types of skill learning and the brain areas involved?
Types of Skill Learning & Brain Areas Involved
Different Types of Skill Learning
1. Sensorimotor Skills – Involves motor control and coordination (e.g., mirror drawing task).
2. Perceptual Skills – Involves recognizing and processing sensory patterns (e.g., mirror reading task).
3. Cognitive Skills – Involves problem-solving and planning (e.g., puzzles).
Brain Areas Involved
• Basal Ganglia（基底神经节） – Crucial for all three skill types; damage impairs skill learning.
• Motor Cortex（运动皮层） & Cerebellum（小脑） – Play key roles in sensorimotor learning, as shown in fMRI studies in healthy individuals.
Key Takeaway
Skill learning depends on basal ganglia for all types, while motor cortex & cerebellum support sensorimotor learning.
How does dopamine serves as a nueromodulator?
Conclusion: Dopamine as a Neuromodulator
Dopamine helps us learn what is good or bad by signaling reward and punishment. When something is better than expected, dopamine increases, making us want to repeat the action. When something is worse than expected, dopamine decreases, discouraging that behavior.
It affects motivation, decision-making, movement, and learning through different brain pathways:
• Reward Pathway (VTA → Nucleus Accumbens) – Increases motivation and reinforces good experiences.
• Decision-Making Pathway (VTA → Prefrontal Cortex) – Helps us plan and make choices.
• Movement Pathway (Substantia Nigra → Basal Ganglia) – Controls habits and motor learning.
Key Takeaway – Dopamine guides behavior by helping us seek rewards and avoid negative outcomes.
What’s the multiple memory system study (one for habit)?
Study Design
Training Phase – Rats were trained to find food at a specific location in a maze.
Probe Trial – Later, rats were released from a different starting position to test if they used spatial (place-based) memory or habitual (response-based) memory.
Findings
Early Training (8 Days) → Hippocampal-Dependent Place Strategy
Rats used spatial memory to go to the same place where food was previously located. This suggests hippocampal involvement in flexible, cognitive-based navigation.
Later Training (16 Days) → Dorsal Striatum-Dependent Response Strategy. Rats switched to a habit-based, stimulus-response strategy, always turning in the same direction regardless of the starting point.
This shift indicates that with extended training, habits take over, relying on the dorsal striatum (caudate nucleus).
Key Takeaways
Early learning relies on the hippocampus, supporting cognitive, flexible navigation.
With prolonged training, memory shifts to the dorsal striatum, forming rigid, habit-based behaviors.
This supports the multiple memory systems theory, where the hippocampus dominates initial learning, but habit learning takes over with repetition.
What’s the trade off and difference between two memory systems
Two Memory Systems:
Hippocampal System – Supports cognitive, place-based, and flexible memory.
Early in training (8 days), rats use a place strategy to find food.
Advantage: Flexible, allows adaptation to environmental changes.
Disadvantage: Slower learning, requires active engagement and effort.
Dorsal Striatum (Caudate Nucleus) System – Supports habit-based, stimulus-response memory.
With extended training (16 days), rats switch to a response strategy, relying on learned motor habits instead of spatial memory.
Advantage: Efficient, automatic, and requires less cognitive effort once learned.
Disadvantage: Rigid, less adaptable to environmental changes; if conditions change, the habit may persist even when it’s no longer useful.
Key Findings & Trade-offs:
Hippocampal learning is flexible but effortful, useful in changing environments.
Habit learning is automatic but inflexible, efficient for stable environments but problematic if conditions change.
Over time, memory shifts from flexible cognitive learning (hippocampus) to automatic habits (dorsal striatum), prioritizing efficiency over adaptability.
What would happen if you remove the rat’s hippocampus or dorsal striatum in the t map task?
Rat will lose habitual/procedural strategy if you removed the striatum, and use place strategy every time.
On the other hand, removing hippocampus will cause rat lose place strategy and rely on habitual processing.
What’s associative learning about?
- Reflexive Conditioning (Cerebellum)
Involves automatic reflexive responses to conditioned stimuli.
Example: Conditioned eye blink – A bell is paired with a puff of air to the eye, leading to an involuntary blink.
Brain Region: Cerebellum（小脑）, which controls learned motor reflexes. - Appetitive/Aversive Conditioning (Amygdala)
Involves emotional learning, associating neutral stimuli with positive (appetitive) or negative (aversive) outcomes.
Amygdala（杏仁核） acts as a saliency detector, encoding fear conditioning, emotional memory, reward, and motivation.
Key Takeaway
Cerebellum controls reflex-based associative learning (e.g., motor responses).
Amygdala is crucial for emotion-based associative learning (e.g., fear, reward, and motivation).
what’s the case study or study about aversive conditioning?
Aversive Conditioning
Amygdala is essential for fear learning – Pairs neutral stimuli (e.g., tone) with aversive events (e.g., shock).
Lesions abolish fear responses – No freezing or autonomic changes (e.g., blood pressure rise).
Human studies – Amygdala damage disrupts fear conditioning and autonomic responses.
Case Study: S.M. (“The Woman Who Knows No Fear”)
Bilateral amygdala damage → No fear of snakes, spiders, horror movies.
Risky behavior → Navigates dangerous places without fear.
Overtrusting strangers, no fear in violent situations.
Key Takeaway
The amygdala is crucial for fear learning, survival instincts, and social caution. Damage prevents fear responses, leading to risk-taking and vulnerability.
what’s the study about appetitive conditioning
Study Design
Rats were allowed to explore two rooms:
Room 1 – Neutral, nothing happens.
Room 2 – Contains a reward (e.g., food, drugs, or a mate).
When given a choice, rats preferred the room where they previously received a reward.
This shows that the rewarded location becomes a conditioned reinforcer.
Key Finding: Role of the Lateral Amygdala
Lateral Amygdala Lesions → Disrupted Place Preference
Rats with lateral amygdala damage did not show a preference for the reward-associated room.
This suggests the lateral amygdala is crucial for forming reward-based place associations.
Key Takeaway
The lateral amygdala is essential for appetitive conditioning, as it helps associate places with rewarding experiences. Without it, reward-driven place preference is impaired.
What’s Amygdala’s Role in Memory Consolidation
Study Overview
Task: Morris Water Maze – Rats learned either a spatial task (hippocampus) or a cued task (striatum).
Intervention: Amygdala stimulated with amphetamine after training to test its effect on memory consolidation.
Retention Test (24h later): Tested whether amygdala activation improved memory.
Results
Spatial Task (Hippocampus-Dependent) → Amygdala activation enhanced spatial memory (rats found hidden platform faster).
Cued Task (Striatum-Dependent) → Amygdala activation improved habit learning (faster response to cues).
Key Takeaway
Amygdala boosts memory consolidation in both hippocampal (spatial) and striatal (habit-based) learning.
Emotional arousal enhances long-term memory, possibly via stress-related mechanisms.
What’s the solution forstudies multiple memory systems with rodents?
when your supervisor has requested that you devise three experiments using the radial arm maze to disentangle the roles of the amygdala, striatum and hippocampus in memory.
Radial Arm Maze Experiments for Multiple Memory Systems
- Hippocampus – Spatial Memory Task
Design: Mice start from different positions; all arms contain rewards to prevent reliance on a single reward location.
Expected Behavior: Normal mice efficiently visit each arm without revisits (win-shift strategy), while hippocampal-lesioned mice explore randomly and make more revisits.
Key Takeaway: Hippocampus is critical for spatial navigation and memory, independent of reward learning. - Amygdala – Emotional Learning Task
Design: Block all but two arms (one lit, one dark) and pair one with appetitive (food) or aversive (shock) conditioning.
Expected Behavior: Normal mice prefer the positive arm or avoid the negative one, while amygdala-lesioned mice show no preference.
Key Takeaway: Amygdala is required for emotional learning, linking places with reward or punishment. - Striatum – Habit/Stimulus-Response Learning Task
Design: Open all arms but light up one arm with a neutral food pellet; once taken, the light turns off.
Expected Behavior: Normal mice learn to associate the light with food and consistently go to the lit arm, while striatum-lesioned mice fail to learn the cue-based response.
Key Takeaway: Striatum is essential for habit-based (stimulus-response) learning, independent of spatial memory.
Overall Takeaway
Hippocampus → Spatial learning (using environmental cues).
Amygdala → Emotional learning (associating places with reward/punishment).
Striatum → Habit learning (stimulus-response associations).
Define “cell assembly” and describe how they are formed.
Cell assembly refers to a network of neurons that fire together repeatedly, leading to strengthened synaptic connections.
Proposed by Donald Hebb, this concept suggests that “neurons that fire together, wire together,” forming the basis of associative learning and memory.
Formation: Repeated activation of connected neurons strengthens synapses through long-term potentiation (LTP), making future activations more efficient.
Distinguish between early and late long-term potentiation (LTP).
Early vs. Late LTP & Protein Synthesis
Early LTP (E-LTP) – Short-Term
Lasts minutes to hours.
Triggered by Ca²⁺ influx → Activates CaMKII & PKA.
Enhances AMPA receptor function & insertion.
No protein synthesis → Temporary effect, fades over time.
Late LTP (L-LTP) – Long-Term
Lasts hours to days (needed for memory storage).
Requires repeated stimulation → cAMP/PKA activates CREB.
Triggers PRP synthesis → Strengthens synapses, promotes spine growth.
Protein Synthesis – Key to L-LTP
CREB activation leads to PRP production, stabilizing tagged synapses.
Essential for long-term synaptic changes & memory consolidation.
Key Takeaway:
E-LTP is short-term, kinase-driven, and fades.
L-LTP is long-term, requires protein synthesis, and stabilizes memory.
What’s long-term potenntiation
LTP is a long-lasting increase in synaptic strength following high-frequency stimulation.
Discovered by Bliss & Lomo (1973) in the hippocampus, demonstrating enhanced synaptic efficiency after stimulation of the perforant path.
serves as a potential mechanism for learning and memory storage.
Key Experimental Findings
Baseline Recording: Low-frequency stimulation establishes synaptic strength baseline (EPSP measurement).
Induction: High-frequency stimulation (simulating learning) is applied to presynaptic axons.
Post-Stimulation Effect: When low-frequency stimulation is applied again, EPSPs remain enhanced, proving synaptic potentiation.
Long-Lasting Effect: LTP persists for hours in vitro, days in vivo, supporting long-term memory formation.
Conclusions
Synaptic strength is influenced by prior activity, demonstrating use-dependent plasticity.
LTP supports associative learning, where repeated activation strengthens connections, storing information more effectively.
Key Takeaway:
LTP is a cellular mechanism for memory storage, strengthening synapses based on prior activation, aligning with Hebbian learning principles
Describe tests examining the role of LTP in learning and memory.
Electrophysiology – Measures synaptic strength changes after LTP induction.
Pharmacological Blockade – Blocking NMDA receptors (key for LTP) impairs spatial learning (e.g., Morris Water Maze).
Optogenetics – Artificially activating LTP-related neurons enhances or disrupts memory recall.
Genetic Manipulations – Mice lacking LTP-related proteins (e.g., CaMKII, CREB) show memory deficits, proving LTP’s role in learning.
Describe how scientists have artificially activated memories.
Optogenetics – Scientists label neurons activated during memory formation and later reactivate them with light, triggering memory recall.
Memory Implantation – Studies have shown false memories can be induced by activating specific neuronal circuits while presenting misleading stimuli.
Example: In rodents, activating hippocampal neurons associated with fear memory made mice “remember” a shock in a different environment (Ramirez & Liu, 2013).
what’s recurrent connection
A recurrent connection refers to neuronal circuits where outputs from neurons loop back as inputs to the same or earlier neurons in the network. This creates a feedback loop that allows for sustained activity, pattern completion, and dynamic processing.
Key Features & Functions:
Sustained Activity – Maintains neural activation over time, crucial for working memory and persistent signal processing.
Pattern Completion – Helps retrieve full memories from partial cues, as seen in hippocampal networks.
Error Correction & Stability – Allows for self-regulation and refinement of neural signals, improving learning and decision-making.
Seen in Multiple Brain Areas –
Hippocampus → Supports memory recall and pattern completion.
Cortex → Important for higher cognitive functions and sensory processing.
Basal Ganglia & Motor Circuits → Involved in motor learning and habit formation.
Key Takeaway:
Recurrent connections allow neurons to influence their own activity through feedback, enabling memory persistence, pattern recognition, and adaptive learning in the brain.
what’s hebbian plasticity
How a Cell Assembly Forms & Functions:
Initial State (A) – Neurons have weak synaptic connections, meaning activation does not spread effectively.
Activation by Input (B) – When an input activates neurons 1, 3, and 5 simultaneously, their connections strengthen through Hebbian plasticity (“neurons that fire together, wire together”). Recurrent connections reinforce activation.
Input Stops (C) – Normally, if the external input ceases, neuronal activity stops unless strong connections have formed.
Pattern Completion (D) – If only one neuron (e.g., neuron 5) is later activated, its strengthened excitatory connections reactivate the entire assembly, completing the pattern. This allows memory retrieval from partial cues.
Sustained Activity (E) – The neural circuit can maintain activity without external input, helping store information for short-term memory or working memory.
Inhibitory Control (F) – Non-relevant inhibitory inputs prevent uncontrolled activation, ensuring efficient processing.
Key Takeaways:
Cell assemblies form through Hebbian plasticity, linking neurons that co-activate.
Pattern completion allows recall from partial cues (e.g., recognizing a song from a few notes).
Recurrent connections sustain memory, making recall faster and more reliable.
Inhibition prevents false activations, ensuring efficient learning and memory processing.
How could we bolster the signal transmission between two neuron and what did evolution did?
What evolution did: Synapse can be potentiated. When we say a synapse can be potentiated, it means that the strength of synaptic transmission can be increased, making it more effective at transmitting signals between neurons. This strengthening happens when the same synapse is repeatedly activated, leading to long-lasting changes in how efficiently the neurons communicate.
How Does Synaptic Potentiation Work?
More neurotransmitter release → The presynaptic neuron releases more glutamate after repeated activation.
Increased receptor sensitivity → The postsynaptic neuron adds more AMPA receptors, making it more responsive.
Stronger postsynaptic response → The receiving neuron generates larger excitatory postsynaptic potentials (EPSPs), making future signals more likely to trigger action potentials.
Structural changes → In long-term potentiation (LTP), synapses can grow new dendritic spines, permanently strengthening the connection.
Key Takeaway:
A potentiated synapse transmits stronger and more efficient signals, which is essential for learning and memory formation in the brain.
What we can design: Decrease distance in synapse cleft. Make synnaptic neuron fire harder and faster with more myelin.
What’s NMDA and AMPA receptor
- AMPA Receptor (α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid Receptor)
Function: Fast excitatory synaptic transmission in the brain.
Activation: Opens when glutamate binds, allowing Na⁺ (sodium ions) to enter, causing depolarization (EPSP).
Role in LTP:
Early LTP: More AMPA receptors are inserted into the postsynaptic membrane, strengthening the synapse.
Result: Increases the efficiency of synaptic transmission, making the neuron more responsive. - NMDA Receptor (N-Methyl-D-Aspartate Receptor)
Function: Acts as a coincidence detector for synaptic plasticity (detects simultaneous pre- and postsynaptic activity and cause that synapse get stronger).
Activation Requirements:
Glutamate binding.
Depolarization to remove Mg²⁺ block.
Allows Ca²⁺ (calcium ions) to enter, triggering signaling pathways for LTP induction.
Role in LTP:
NMDA receptor activation leads to Ca²⁺ influx, which triggers molecular changes that strengthen synapses.
Essential for initiating LTP, but AMPA receptors maintain it.
Key Takeaway:
AMPA receptors = Fast excitatory signaling, strengthens synapses in LTP.
NMDA receptors = Trigger synaptic plasticity, required for LTP induction.
Together, they regulate learning, memory, and synaptic strengthening in the brain.
what’s signaling cascade when calcium comes in the hippocampal synapse?
Ca²⁺ Influx → Activates Signaling Cascade
NMDA receptor opens, allowing Ca²⁺ entry into the postsynaptic neuron.
AMPA Receptor Phosphorylation → More Na⁺ Influx
CaMKII phosphorylates (P) AMPA receptors, making them more sensitive and increasing Na⁺ intake, strengthening synaptic response.
Nitric Oxide (NO) Release → Retrograde Signaling
Ca²⁺ triggers NO synthase, producing nitric oxide (NO).
NO diffuses back to the presynaptic neuron (retrograde signaling).
More Vesicle Release → More Glutamate Release
NO stimulates the presynaptic neuron, increasing vesicle fusion and glutamate release.
More AMPA Receptors → Stronger Synapse
Higher glutamate levels further increase AMPA receptor insertion, reinforcing the circuit.
Final Outcome:
More Na⁺ influx → Stronger postsynaptic response.
More glutamate release → Reinforces synaptic efficiency.
Synapse becomes more responsive → Strengthens neural circuits for memory storage.
what’s the fundamental properties of LTP
Long term potentiation. Where’s potentiation meaning a more excitable postsynaptic neuron, and long term meaning these differences happen for an extended period of time.
The fundamental properties are: Synaptic transmission: They require synaptic transmission to occur (you can’t strengthen a synapse that isn’t firing or have no connection). No relief of MG2+ then no LTP.
Cooperatively. Sufficient spatiotemporal summation, with some amount of depolarization (summation) can cause the magnesium release and cause LTP to occur. For example, when experience significant enough/ LTP occur due to activate enough neurons and presynaptic activity which encoded information.
Associativity: Strong input - relieves Mg2+block occurs LTP. Association between important stimulus and something co-occurring, can be used later to predict that stimulus. For example, people remember things clearly at the day of 9-1-1.
Synapse specificity: LTP only occurs at active synapses, and it prevents storage of unrelated information. Potentially there could be enough depolarization to remove the magnesium block for no LTP’s synapse, but you also need glutamate to be binding at the same time to occur LTP.
What’s PRP and cAMP and how are they related to what we’ve covered so far
- PRP (Plasticity-Related Proteins) – Memory Maintenance
Definition: PRPs are proteins synthesized during LTP that help strengthen and stabilize synaptic changes for long-term memory storage.
Role in LTP:
Triggered by NMDA receptor activation & Ca²⁺ influx.
Controlled by transcription factors like CREB, which turns on genes needed for long-term synaptic changes.
Supports dendritic spine growth & AMPA receptor insertion, ensuring lasting synaptic potentiation.
✅ Key Connection: PRPs are essential for the transition from Early LTP (E-LTP, temporary synaptic strengthening) to Late LTP (L-LTP, long-lasting changes). - cAMP (Cyclic AMP) – A Key Signaling Molecule in LTP
Definition: cAMP is a second messenger that regulates intracellular signaling pathways, essential for memory consolidation.
How It Works:
Ca²⁺ influx through NMDA receptors activates adenylyl cyclase (AC), converting ATP into cAMP.
cAMP activates Protein Kinase A (PKA), which:
Enhances AMPA receptor function (short-term synaptic changes).
Activates CREB, leading to PRP synthesis for long-term synaptic strengthening.
✅ Key Connection: cAMP is the signal that links Ca²⁺ influx to PRP production, making L-LTP and long-term memory possible.
How do PRP knows where to go
Tag setting and tag synapses:
✅ PRPs are directed to specific synapses via “synaptic tagging.”
1. Synaptic Tagging
• When a synapse is stimulated, it sets a molecular tag that marks it for PRP capture.
• This involves Ca²⁺ influx, kinases (CaMKII, PKA), and local synaptic modifications.
2. PRP Synthesis & Distribution
• Strong stimulation triggers CREB activation, leading to global PRP synthesis in the soma.
• PRPs travel throughout the neuron but only stabilize at tagged synapses.
3. Synaptic Capture
• Only tagged synapses can retain PRPs, ensuring LTP is selectively stabilized at relevant connections.
Strong vs. Weak Stimulus Tags in STC
✅ Both strong and weak stimuli can create synaptic tags, but only strong stimuli trigger PRP synthesis.
1. Strong Stimulus → Tagging + PRP Synthesis
• Generates both a synaptic tag and triggers PRP production via CREB activation.
• PRPs stabilize LTP at both strong and weakly stimulated synapses (if tagged).
2. Weak Stimulus → Tagging Without PRP Synthesis
• Creates a tag but does not initiate PRP synthesis.
• If PRPs are already available (from a nearby strong stimulus), the weakly tagged synapse can capture PRPs, stabilizing LTP.
• If no PRPs are present, the synapse undergoes only early LTP, which fades over time.
Key Takeaways
• Tags identify synapses that need PRPs; PRPs stabilize LTP.
• Strong stimuli trigger both tagging & PRP production.
What’s the two types of associativity.
LTP can associate weak and strong stimuli on different timescales.
1. NMDAR-Dependent Associativity (Milliseconds)
Weak synapse uses depolarization from nearby strong synapse to remove the Mg²⁺ block from NMDA receptors.
Allows stimuli within ~1 second to associate.
2. PRP-Dependent Associativity (Minutes to Hours)
Weak synapse sets a tag but cannot produce PRPs.
If a strong synapse triggers PRP synthesis, the weak synapse can capture PRPs, stabilizing LTP.
Enables stimuli hours apart to associate.
Key Takeaway:
NMDAR-dependent = Short-term (seconds), requires depolarization sharing.
PRP-dependent = Long-term (hours), relies on PRP availability for synaptic tagging.
What’s the study about NMDA receptors in associative memory recall test.
Two groups of mice, one knocked out of NMDA receptors (mutant group) and one group as control group.
The methods is Morris water maze style test, and is comparing full cue for platform and partial cue and even no cue condition.
Observation: Control group have remain potentiated more active in the future if activated the cells at the start, but mutant group did not. So the neuron pathway didn’t be more efficient.
Conclusion: Both group find platform with full cue, but mutant group did much worse when it comes to partial cue, while control group did ok. Interestingly, mutant group performed the same as partial cue condition when no cue, and control group did the worse in the entire study when no cue.
Shows that NMDA receptors for pattern completion and for linking the different aspects of memory together. Or allowing LTP to occur that connect those different aspects of memory that occur at the same time.
What’s channelrhodopsin and Halorhodopsin?
These are two types of membrane receptors that respond to light.
The C one will open up and let sodium (excitory) in when shined light of a specific wavelength.
The H one will open up and let chloride ions (Inhibitory) in when shined light of a specific wavelength.
What’s the fear induced experiment
Put rat into a context, and teach it that context A is a bad dangerous place by shocking rats when they are in the room. And certain pattern of active hippocampal cells are forming this fearful memory. When put rat in safe context but light stimulation on these patterns, the animal try to escape but failed and become freezing as they are scared in context A. Illustrating that false/artficial memory could be implemented in animal like rat (kinda like PTSD)!
Indicating that even in a new context, little trigger can start that pattern and they enter the memory. As memory is attached to a full physiological response because it was attached to trauma.
Additionally, it’s being found that mice with neurons expressing channelrhodopsin and YFP under c-fos promoter only freeze when the light is on. And mice without channelrhodopsin but only YFP under c-fos promoter do not freeze at all.
So they conclude that memories are stored in discrete networks or discrete populations of neurons in the hippocampus (potentially elsewhere). And then these neurons that encode a memory or a populations of neurons are called engrams - the population of neurons that contribute to a specific memory.
What’s the study about creating a false memory in the hippocampus.
Rat were placed in environment A and it’s safe. But Rat were shocked in environment B and the pattern of cell for environment A was activated by light. So rat is scared even A is safe, because its pattern is associated with shocking. But if we put them in new place C, they are no longer scared.
Another study: Rat exploring a room. And turns on scary memory in part of the room, and its found the exploration route were much more on the opposite side where scary memory comes in. But they rat will also spend more time in one part of the room if there is good memory pattern lighted.
So it’s proof of concept that you can switch bad memory to good memory, or vice versa.
What’s standard model for memory consolidation
The Standard Model explains how memories transition from hippocampal dependence to neocortical storage, allowing long-term retrieval without hippocampal involvement.
Step-by-Step Process:
Before Learning
Neocortical circuits are independent and unlinked (not yet forming memory connections).
The hippocampus is not initially involved.
Cellular/Synaptic Consolidation (Learning Phase)
The hippocampus rapidly encodes new information and strengthens synaptic connections in the neocortex via LTP.
This forms the initial memory trace (short-term memory).
Systems Consolidation (Memory Integration)
Over time, hippocampal activity strengthens neocortical connections, binding circuits together.
The memory trace gradually shifts from the hippocampus to the neocortex, making it more stable.
Final Stage: Fully Consolidated Memory
A “carbon copy” of the memory is stored in the neocortex, independent of the hippocampus.
Once well-learned, memory retrieval relies on cortical circuits, and the hippocampus is no longer needed.
Key Takeaway:
Initially, the hippocampus is essential for memory formation.
With time, memory shifts to the neocortex, becoming independent of the hippocampus.
This explains why patients with hippocampal damage (e.g., HM) can recall old memories but struggle to form new ones.
The content of Review in LTP
Short term note: 3 types of memory + associated brain region. Emotional valance-conditioned association - Amygdala. Reflexive memory (Associations) -
cerebellum. Non declarative-procedural - (striatum), episodic - spatial - Hippocampus.
LTP long term memory- protein synthesis required. Related proteins: C-FOS, plasticity related proteins (Helps long-term memory to form).
These
protein may allow cell to gain more membrane receptor and then grow.
LTP short - NMDA receptor (it get synapse excited), related proteins: Mg2+ and AMPA R. Ca2+, calcium neurons rushes in and causes
signalling quascade.
More release of NT (Glutamate). 2. Add more AMPA receptors. 3. Phosphorylate AMPA Receptors.
Long version:
The main difference between early and late LTP is one (late) required protein synthesis while the other (early) do not.
PRP is plasticity related proteins is like the general term for the group of proteins. And plasticity related proteins are going to allow the cell to do all the things to help a long term memory form, which is strengthen a synapse between two cells that have been activated during a memory. They might be related to growing new synapses as well.
These proteins might allow the cell to create more membrane receptors and grow.
When it comes to receptors: NMDA (gets you excited and its like a drug, get synapse more excited as well).
NMDA receptors: They need the cell to become very depolarize to be activated. So basically NMDA releases a plug when a synapse is sufficiently active and means something important is going on. Which turns our attention on and allows the system to have calcium signaling cascade.
AMPA receptors: Normally bind glutamate (most common excitatory neurotransmitter), they open and let sodium in when bind with glutamate. So sodium ions rush in and depolarize the cell, and then cell may be depolarized, and thus sending an action potential. In the end, if lots of glutamate and sodium coming that will eventually unplug the magnesium plug. And now it will cause more depolarization but with calcium ions comes in, which leads to signaling cascade.
Signaling cascade leads to three things help to strengthen the synapse:
1 More neurotransmitter, with more of these we will have more AMPA receptors being bound then we have more depolarization happen and that’s a more excitable synapse. Additionally, The calcium signaling leads to the production of nitrous oxide, which diffuses out of the cell, gets into the presynaptic cell, and cause it to release more glutamate or make move vesicles go and bind and release.
2. Add more gates,
3. Phosphorylate AMPA receptors: If we energize these AMPA receptors, they open up more and we can get more sodium in.
In particular, signaling cascade makes the synapse more efficient, and it tells us the cell what it thinks is important by lead transcription of new proteins in the cell. And potentially change the genetic code which may help us make more synapse, and maybe go through associativity, connect some other details that seems important that might be active at the same time.
What’s the evidence for standard model?
Standard model theory suggest that memory will eventually stored in area of brain cortex instead of hippocampus alone.
There was study about context fear memory. Where researchers place rat into a previously shocking context environment (now safe), the control group of mice (no lesion) shows fear/freezing behaviour at first day and shows less freezing behaviour when time goes by, until 30 days, it shows a level of freezing behaviour that’s no significant different than the hippocampus lesion group. While the hippocampus group shows no freezing behaviour the first day of lesion, the freezing behaviour starts to increase days by days and demonstrate that they can somehow have the fear memory without hippocampus.
Another study: People with epilepsy were tested. (Pilot shows, shows that sucks and can’t make to season two), and people were tested about how much they could remember for these show’s character at different stages when they are going with ECT (shocking, “lesion” that interrupt the memory) treatment in their hippocampus. Two group, one receive treatment one did receive. Same patterns was found, group have no “lesion” remember much more than the “lesion” group, but when times pass. Control group remember less and lesion group remember more, until the 2500 days, their memory is about the same level.
what’s the difference between standard model and trace-transformation theory?
Standard Model:
Memory is transferred from the hippocampus to the neocortex without changing its form.
The neocortex stores both facts (semantic memory) and detailed episodic memories.
Once fully consolidated, the hippocampus is no longer needed for retrieval.
Multiple Trace / Trace-Transformation Theory:
Different types of memory are stored differently:
Semantic memory (general facts) → stored in the neocortex.
Episodic memory (detailed, context-rich) → remains in the hippocampus.
Over time, episodic memories transform into more generalized, schematic versions in the neocortex.
The hippocampus is always required for retrieving detailed episodic memories.
Key Takeaway:
Standard Model = The entire memory (episodic + semantic) moves to the cortex.
Multiple Trace Theory = The hippocampus always stores detailed episodic memories, while only the semantic/generalized version is stored in the cortex.
What’s the evidence of multiple trace theory?
Fear memory shifts from episodic (context-specific) to semantic (generalized) over time.
Early Stage → Mice freeze only in the trained box (episodic memory, hippocampus-dependent).
Later Stage → Fear generalizes to novel environments, suggesting memory transformation.
Early Hippocampal Lesion → Erases fear memory (hippocampus needed for recent recall).
Late Hippocampal Lesion → Mice still freeze in novel contexts (neocortical memory persists).
Key Takeaway:
consolidation creates a separate neocortical-semantic version of the memory
Episodic memory fades, but generalized fear remains.
Supports MTT: Hippocampus stores details, cortex stores transformed memories.
What about the relationship between consolidation and sleep
Memories are replayed and strengthened during sleep, aiding consolidation.
Key Findings:
Hippocampal place cells fire during maze navigation.
During sleep, the same pattern replays, but at ~20x speed.
Replay occurs in both forward and reverse directions.
Disrupting this replay (waking mice up) impairs memory.
Mice struggle with similar mazes if their sleep replay is interrupted.
Key Takeaway:
Sleep is critical for memory consolidation.
Replaying experiences strengthens memory, helping retention and learning.
Disrupting sleep impairs memory formation.
What we found in the cellular and systems reconsolidation in the hippocampus?
Train rats by shocking (fear conditioning) and teach them the box is scary, and then give one group of mice anisomycin (PRP inhibitor) after reacting the fear memory while one do not. And the researchers found that the group injected with drug shows much less freezing behaviour after a reactivated hours later.
Results: If we interrupt the consolidation process after a memory has been reactivated, you actually reduce the ability to remember that memory.
Another test shows that the main difference is re-activating the memory condition (Both group declined freezing behaviour with the injection of anisomycin without re-activating the scary context). Additionally, if you reactivate the memory, it returns to a labile state in both condition, and no matter how long it delay, the memory is labile state after 15 days of initial activation if re-activated, and it works in this pattern after 45 days of initial activation as well (changeable by interruption).
What’s found in following study: Reconsolidation process happens over about two days, as the anisomycin injected mice shows a closer level of freezing behaviour with control mice after two dues of lesion. So conclusion is reactivation or recall of a memory, there’s a two day period where that memory is hippocampal dependent. And it needs protein synthesis in the hippocampus to form the memory as strong as it was initially. Furthermore, consolidating it self is a long process but once you remembered it, but the reconsolidation for this memory is faster as there’s only a two days of labile period before becoming stable again.
Is LTP important for memory consolidation?
Yes, Long-Term Potentiation (LTP) is crucial for memory consolidation.
Why?
LTP strengthens synapses, making neural circuits more efficient for long-term storage.
During learning, high-frequency stimulation enhances synaptic transmission, a key mechanism for consolidating information.
LTP stabilizes memories by reinforcing connections in the hippocampus and neocortex, enabling long-term storage.
Blocking LTP disrupts memory formation, showing its necessity for consolidation.
Key Takeaway:
LTP is the cellular basis of memory, enabling stable and efficient storage of learned information. 🚀
What’s reconsolidation?
Reconsolidation is a process where retrieved memories become unstable and undergo modification before being stored again.
Key Points:
After consolidation, memories seem stable but can become labile when recalled.
The brain “reprocesses” memories, allowing strengthening, updating, or altering details.
This flexibility is adaptive, improving learning and prediction.
Clinically important: PTSD treatments may alter traumatic memories to reduce distress.
Key Takeaway:
Memories aren’t static—retrieval can destabilize them, making them modifiable before reconsolidation.
What’s the study of human reconsolidation talks about?
Memory reactivation makes memories unstable and vulnerable to disruption before reconsolidation.
Experiment Design:
Participants read a story (initial learning phase).
Electroconvulsive Therapy (ECT) was applied before recall to test reconsolidation disruption.
Groups:
Group A (Red): ECT → 1-day delay → Recall
Group B (Blue): ECT → 90-min delay → Recall
Group C (Orange, Control): No ECT → 1-day delay → Recall
Findings:
Group A (1-day delay after ECT, reactivated memory)
→ Significant memory impairment
→ Memory was retrieved before reconsolidation finished, so ECT disrupted stabilization.
Group B (90-min delay after ECT, reactivated memory)
→ No significant memory impairment
→ Memory was still in initial consolidation, not yet reactivated for reconsolidation.
Group C (No ECT, control group)
→ Intact memory recall
→ Normal memory consolidation and reconsolidation.
Key Takeaway:
Memories become unstable upon retrieval and must go through reconsolidation to remain stable.
Disrupting reconsolidation (ECT in Group A) impairs memory, but disrupting early consolidation (Group B) does not.
Supports reconsolidation as a distinct process separate from initial consolidation.
