Lectures 10-12 Flashcards
Explain the theoretical role of theta and gamma oscillations in hippocampal memory encoding, as depicted in the model.What are the two types of long term memory?
Declarative: the conscious recall of facts and events.
Non-Declarative: unconscious memory for skills, habits and procedures.
What are the two types of declarative memory?
Episodic: memory of personal experiences and events.
Semantic: memory of general knowledge and facts.
What are the two types of non-declarative memory?
Procedural Learning: the unconscious acquisition of motor and cognitive skills through repetition and practice.
Conditioning: where learning occurs through associations between stimuli and responses.
Explain the key distinction between behaviourist and cognitivist explanations of T-maze learning in rats.
Behaviourists propose that rats develop a habit-based procedural memory (response strategy) where they learn to make a specific turn (e.g., always turn right).
Cognitivists argue that rats develop a mental map-based declarative memory (place strategy) where they remember the spatial location of the reward relative to environmental cues.
How does the T-maze rotation experiment help differentiate between procedural and declarative memory systems?
When the T-maze is rotated 180°, rats using a response strategy (procedural memory) will make the same physical turn regardless of spatial orientation, while rats using a place strategy (declarative memory) will navigate to the same spatial location using environmental cues, taking a different physical turn than during training.
Describe the neural substrates that support response vs. place learning strategies in the T-maze.
Response learning (procedural memory) relies on the striatum and is habit-based, while place learning (declarative memory) depends on the hippocampus and involves spatial mapping.
Lesion studies demonstrate that damage to these dissociable brain regions selectively impairs the corresponding strategy.
What is the current understanding of how procedural and declarative memory systems interact during spatial learning tasks?
Both memory systems exist simultaneously and compete for behavioural control.
The dominant system depends on factors including task demands, training duration, and individual differences.
With extended training, control often shifts from hippocampal-dependent declarative memory to striatal-dependent procedural memory as behaviours become habitual.
Describe a classic T-maze study investigating multiple memory systems, including methodology and key findings.
METHODS:
* The T-maze paradigm was implemented with rats to dissociate procedural and declarative memory systems.
* Rats were food-restricted to 85% of free-feeding weight.
* The apparatus consisted of a T-shaped maze with a start arm and two goal arms in a room with distinct visual cues.
* During acquisition, rats were trained to find food consistently in one arm (e.g., right arm).
* After reaching criterion performance (90% correct choices), the critical probe test involved rotating the maze 180° relative to the room’s environmental cues.
* Two experimental groups were tested: rats with hippocampal lesions and rats with dorsolateral striatal lesions.
* Control rats received sham surgeries.
RESULTS:
* Control rats showed a mixed strategy preference, with approximately 60% using a place strategy (navigating to the same spatial location) and 40% using a response strategy (making the same turn).
* Hippocampal-lesioned rats exhibited a strong bias toward response strategies (>85%), demonstrating impaired place learning but intact procedural memory.
* Striatal-lesioned rats showed the opposite pattern, with >80% using place strategies, indicating impaired procedural memory but preserved declarative memory.
* With extended training, control rats gradually shifted from predominantly place strategies to response strategies, suggesting procedural memory dominates with habit formation.
These findings confirm that multiple memory systems operate in parallel, rely on dissociable brain regions and compete for behavioural control depending on task demands and training conditions.
Draw and example of the T-maze learning paradigm.
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What have numerous experiments in T-maze learning concluded about place vs response strategies being used?
“Place” strategy is used if salient extra-maze cues are present (declarative memory).
“Response” strategy when ‘over-trained’/cues are absent (procedural memory).
Describe the Packard & McGaugh experiment on multiple memory systems, including methodology, results, and implications for understanding memory system competition.
METHODOLOGY:
* Rats were trained on a T-maze for 1 week (4 trials/day) to find food consistently in one arm.
* After week 1, the maze was rotated 180° and performance tested in a probe trial.
* The maze was then returned to its original position for a second week of training.
* After week 2, another 180° rotation probe trial was conducted.
* Cannulae were surgically implanted in both the hippocampus and striatum.
* During probe trials, lidocaine (local anesthetic) or saline was injected to temporarily inactivate specific brain regions.
* The striatum included the caudate nucleus, putamen (collectively referred to as CPu), and nucleus accumbens (NA).
RESULTS:
Probe Trial 1 (Week 1):
* Control rats (saline injection) predominantly used place strategy (85%).
* Hippocampal inactivation disrupted place learning, reducing performance to chance level (50%).
* Striatal inactivation had no effect on performance (87% place strategy).
Probe Trial 2 (Week 2):
* Control rats shifted to using response strategy (81%).
* Hippocampal inactivation had no effect on response performance (87%).
* Striatal inactivation abolished response memory, causing rats to revert to place strategy (92%).
IMPLICATIONS:
* The study demonstrated a double dissociation between memory systems: hippocampus mediates place learning while striatum mediates response learning.
* Initial learning relies on cognitive mapping (declarative memory) in the hippocampus.
* Extended training (“overtraining”) leads to development of habit-based response strategy (procedural memory) in the striatum.
* Both memory systems coexist simultaneously but compete for behavioural control.
* The transition from declarative to procedural memory with extended training suggests an adaptive shift from flexible to more efficient but rigid memory systems.
The experiment proved that multiple memory systems operate in parallel, with each capable of compensating when the other is inactivated.
What is the primary function of the hippocampus in spatial navigation?
The hippocampus mediates place learning through cognitive mapping.
It enables the formation of declarative memories about spatial relationships and environmental cues, allowing navigation based on allocentric (world-centred) coordinates.
What is the primary function of the striatum in learned behaviours?
The striatum mediates response learning and habit formation.
It enables procedural memory development, allowing for automatic, stimulus-response associations that become increasingly efficient but less flexible with practice.
How do declarative and procedural memory systems interact during skill acquisition?
Initially, declarative memory (hippocampal) dominates, providing flexible, conscious control.
With extended practice, procedural memory (striatal) gradually takes over, creating more efficient, automatic responses.
Both systems operate in parallel and compete for behavioural control depending on task demands and training duration.
What comprises the striatum and what is its general role in memory?
The striatum includes the caudate nucleus, putamen (collectively called CPu) and nucleus accumbens.
It plays a central role in procedural memory, habit formation, and reward-based learning, enabling automatic stimulus-response associations that require minimal conscious attention.
How does the brain maintain multiple memory representations of the same information?
The brain encodes information in parallel across different neural systems.
The hippocampus creates context-rich, flexible representations (declarative memory).
The striatum simultaneously develops stimulus-response associations (procedural memory).
These systems can operate independently when one is compromised, demonstrating adaptive redundancy in memory organization.
What is the role of the medial temporal lobe (MTL) in declarative memory? Explain why we know this.
The medial temporal lobe, including the hippocampus, is critical for declarative memory formation.
Evidence from patients like H.M. and animal studies demonstrates its essential role in creating new declarative memories.
However, the MTL is not required for short-term memory maintenance or for retrieving remote long-term memories that were acquired long before hippocampal damage.
This suggests the MTL serves as a temporary processing system for memory consolidation rather than a permanent storage site.
Explain the apparent paradox that hippocampal damage impairs declarative memory while sparing certain forms of memory.
Despite being critical for declarative memory, hippocampal damage does not impair:
- Short-term memory, as demonstrated by MTL amnesics performing normally on delayed non-matching to sample (DNMTS) tasks with brief delays.
- Remote long-term memories acquired well before the damage occurred.
- Procedural memory and implicit learning.
This dissociation suggests the hippocampus is specifically involved in the initial encoding and consolidation of declarative memories, after which these memories become increasingly independent of hippocampal function through systems consolidation.
What evidence from patient H.M. and other MTL amnesics informs our understanding of memory systems?
Patient H.M. and other MTL amnesics demonstrate:
- Severe anterograde amnesia (inability to form new declarative memories).
- Temporally graded retrograde amnesia (recent memories impaired, remote memories preserved).
- Preserved procedural learning and short-term memory.
- Normal performance on tasks with very brief delays.
These patterns reveal a memory system where the MTL is crucial for converting short-term experiences into long-term declarative memories but is not the site of permanent storage or necessary for all types of memory processes.
Describe Eichenbaum’s modified T-maze experiment and its significance for understanding hippocampal function beyond spatial mapping.
In Eichenbaum’s modified T-maze experiment (1999), rats learned to alternate between left and right turns to obtain rewards, creating a figure-eight pattern of movement.
Hippocampal recordings revealed place cells in the central stem that fired differentially based on the upcoming turn direction (left vs. right).
These cells maintained spatial specificity (fired in the same location) but showed context-dependent firing rates based on future behavioural choices.
This demonstrated that hippocampal neurons encode both spatial information and non-spatial elements (planned actions), supporting the view that the hippocampus combines multiple elements of experience to form declarative memories rather than functioning solely as a spatial mapping system.
What evidence from Eichenbaum’s T-maze studies suggests that hippocampal place cells encode more than just spatial location?
Eichenbaum found that certain hippocampal place cells in the stem of a modified T-maze fired at the same spatial location but showed significantly different firing rates depending on whether the rat was planning to turn left or right.
Some cells fired more strongly before leftward turns, while others fired more vigorously before rightward turns.
These cells maintained their place fields (spatial coding) while simultaneously encoding future behavioral choices (non-spatial information).
This prospective coding demonstrates that hippocampal neurons integrate spatial, behavioural, and temporal elements into unified representations, supporting episodic memory formation rather than just spatial mapping.
How does prospective coding in hippocampal neurons contribute to declarative memory formation?
Prospective coding occurs when hippocampal neurons fire differently in the same location based on planned future actions, as seen in Eichenbaum’s T-maze studies.
This neural mechanism allows the hippocampus to:
* Link spatial contexts with behavioural choices
* Integrate past experience with future intentions
* Form relational connections between elements of an experience
* Create temporal sequences necessary for episodic memory
This ability to combine spatial, behavioural and temporal elements enables the formation of complex declarative memories that extend beyond simple spatial mapping, supporting the hippocampus’s broader role in episodic and relational memory.
Describe the DNMTS (Delayed Non-Match to Sample) task used to dissociate spatial and non-spatial memory functions of the hippocampus.
The DNMTS task used plastic cups filled with scented sand (9 different odours like cinnamon or coffee) placed randomly at 9 fixed locations.
Rats received food rewards if the current odour did NOT match the previous trial’s odour.
This task design specifically dissociated spatial components (cup location) from non-spatial components (odours, match/mismatch condition).
Hippocampal neuron activity was recorded as rats approached cups, allowing researchers to identify cells responsive to different task variables or combinations of variables.
Describe the methods and results of Eichenbaum’s studies investigating hippocampal encoding of non-spatial information.
METHODS:
* Delayed Non-Match to Sample (DNMTS) task was implemented with rats.
* Plastic cups filled with sand were scented with 1 of 9 common odours (cinnamon, coffee, etc.).
* On each trial, a cup was placed randomly at one of 9 fixed locations in the testing arena.
* Food rewards were buried in the sand if the current odour did NOT match the previous trial’s odour.
* Microelectrodes were implanted in the hippocampus to record neural activity as rats approached cups.
* In a separate transitive inference study, rats learned hierarchical odour pair associations (A>B>C>D>E) where certain odours were rewarded depending on their pairing.
* Probe trials tested novel combinations (B vs. D requiring inference; A vs. E not requiring inference).
RESULTS:
* Approximately 65% of recorded hippocampal neurons responded to one or more task variables.
* One-third of responsive cells had spatial firing correlates, another third had non-spatial correlates.
* Some cells fired selectively to specific odours regardless of location (odour cells).
* Other cells fired at specific locations regardless of odour (place cells).
* The majority of cells responded to combinations of cup position, odour identity, match/mismatch status, and approach initiation.
* In the transitive inference task, rats with intact hippocampi successfully chose B over D in probe trials, demonstrating relational memory.
* Hippocampal damage specifically impaired transitive inference judgments while preserving direct associations (A vs. E).
These findings demonstrate that hippocampal neurons encode multiple dimensions of experience beyond spatial mapping, supporting Eichenbaum’s “memory space” concept integrating space, time, and memory.
Explain Eichenbaum’s “Memory Space” hypothesis and how it reconceptualises hippocampal function beyond spatial mapping.
It proposes that the hippocampus creates a multidimensional framework that organises memories according to three key principles:
Sequential encoding:
* Encodes episodes as sequences of events and places
* Each hippocampal cell represents a specific segment containing information about stimuli, behaviour and spatial position.
* Creates temporal organisation of experience
Relational linking:
* Connects separate episodes at common elements (events or places)
* Creates associations between otherwise distinct experiences through shared features
* Some cells encode combinations unique to single events
* Others encode features common across multiple experiences
Flexible network construction:
* Builds an integrated relational network supporting flexible memory expression
* Enables novel inferences between indirectly related elements
* Allows “navigation” through conceptual space similar to physical space
This model expands hippocampal function beyond spatial mapping by:
* Explaining how the same neural architecture supports both spatial navigation and non-spatial cognition
* Accounting for why hippocampal damage selectively impairs relational memory while sparing direct associations
* Providing a mechanism for transitive inference and flexible recombination of memory elements
* Reconciling spatial and non-spatial functions within a unified theoretical framework
The Memory Space hypothesis represents a significant shift from viewing the hippocampus as primarily a spatial mapping system to understanding it as creating a multidimensional cognitive map of experience.
What types of hippocampal neuron response patterns were observed in Eichenbaum’s DNMTS task, and what do they reveal about hippocampal function?
Eichenbaum’s recordings revealed multiple response patterns:
* Odour cells (place-independent) - fired selectively to specific odours regardless of location
* Place cells (odour-independent) - fired at specific locations regardless of odour
* Match/mismatch cells - responded based on whether current trial matched previous trial
* Combination cells - fired to specific combinations of location, odour and match/mismatch status
* About 65% of hippocampal neurons responded to one or more task variables, with most cells responding to combinations of factors.
This shows the hippocampus creates integrated representations of multiple memory dimensions beyond just spatial mapping.
What specific evidence from lesion studies in the transitive inference paradigm demonstrates the hippocampus’s selective role in relational memory processing?
METHODS:
Rats were trained on a hierarchical odor preference task (A>B>C>D>E) with overlapping odor pairs.
After training, selective lesions were performed on either:
* Fornix (hippocampal output pathway)
*Parahippocampal region (PHR; perirhinal + entorhinal cortices)
Performance was tested on three distinct trial types to dissociate memory functions.
RESULTS:
Both fornix-lesioned and PHR-lesioned rats showed:
* Normal performance (~75-80% correct) on directly trained premise pairs (BC+CD)
* Perfect performance (~100% correct) on end-anchored pairs (AE)
* Severely impaired performance (at chance level, ~50%) on BD probe trials requiring transitive inference
This double dissociation demonstrates that:
* The hippocampal system is specifically required for inferential relationships between separately learned memories
* Direct associations can be formed and maintained without hippocampal involvement
* The critical function of the hippocampus is organising relationships between memories rather than storing individual memories themselves
The anatomical circuit (cortex → parahippocampal region → hippocampus → back to cortex) forms an integrated system where disruption at any point specifically impairs relational processing while preserving simpler forms of memory.
What is an auto-associative network in the hippocampus and where is it primarily found?
An auto-associative network features recurrent connections that feed back to the same neurons that initiated firing.
This network architecture is primarily implemented in the dentate gyrus of the hippocampus.
Auto-associative networks are specialized for pattern completion, allowing complete memories to be retrieved from partial inputs.
They enable pattern separation, the process of distinguishing similar experiences as distinct neural representations.
These networks are limited to single item/pattern retrieval rather than processing sequential information.
What is a hetero-associative network in the hippocampus and where is it primarily found?
A hetero-associative network features unidirectional connections between different neuronal populations.
This network architecture is primarily implemented in the CA3 region of the hippocampus.
In hetero-associative networks, activated neurons trigger firing of subsequent elements in a sequence, but not previous ones.
They are specialized for sequential memory processing and the temporal organization of information.
These networks support memory for ordered events in episodic memories, enabling forward-directed memory retrieval.
How do auto-associative and hetero-associative networks in the hippocampus work together to support memory?
The dentate gyrus performs pattern separation through sparse coding, distinguishing similar inputs.
The CA3 region implements both network types through its unique connectivity patterns.
Auto-associative properties support pattern completion, retrieving complete memories from partial cues.
Hetero-associative properties enable sequential processing, maintaining temporal relationships between events.
This dual architecture allows the hippocampus to distinguish between similar experiences while preserving their relationships.
The complementary networks enable both retrieval of discrete memory elements and their sequential organization.
This integrated system provides the neural basis for organizing memories in a relational “memory space” as proposed by Eichenbaum.
Explain the temporal organization of hippocampal firing patterns in terms of “vertical” versus “horizontal” encoding.
Vertical firing patterns represent individual memory elements (items) that are encoded and retrieved rapidly.
These item-specific patterns show repeated activation across the same cells when processing single components of a memory.
Horizontal firing patterns stretch across multiple cells and represent the complete sequential memory.
The horizontal patterns operate on a slower timescale than vertical patterns, reflecting the additional time needed to process relationships between elements.
This temporal organization creates a matrix where:
* Fast vertical processing = individual items/elements
* Slow horizontal processing = complete sequential memories
This dual temporal structure enables the hippocampus to simultaneously maintain both discrete elements and their sequential relationships within a memory.
What is the functional significance of different temporal scales in hippocampal memory encoding?
Rapid temporal processing (vertical patterns) allows quick recognition and retrieval of individual memory elements.
Slower temporal processing (horizontal patterns) enables the integration of elements into coherent sequential memories.
The interaction between fast and slow processing creates a hierarchical memory structure.
This temporal hierarchy supports both pattern completion of individual elements and sequential organization of complete memories.
The different timescales allow the hippocampus to efficiently process both the content of memories (what) and their temporal structure (when).
What is pattern completion in hippocampal processing and what is its functional significance?
Pattern completion is the ability to reconstruct a complete memory from partial or degraded input.
For example, when you see part of a familiar room, you can recall the entire layout and contents.
This process occurs primarily in the CA3 region through auto-associative networks.
When a subset of neurons representing part of a memory is activated, recurrent connections enable the network to activate the full ensemble of neurons associated with the complete memory.
Pattern completion is crucial for memory retrieval in real-world conditions where cues are often incomplete or ambiguous.
What is pattern separation in hippocampal processing and what is its functional significance?
Pattern separation is the process of transforming similar inputs into distinct, non-overlapping neural representations.
For example, being able to form separate memories of two different birthday parties despite their similar features.
This process occurs primarily in the dentate gyrus through sparse coding.
The dentate gyrus has many more neurons than its input region (entorhinal cortex), allowing similar input patterns to be distributed across different neural populations.
Pattern separation is crucial for reducing interference between similar memories and maintaining distinct episodic memories.
Without effective pattern separation, similar experiences would overwrite each other, leading to confusion and memory interference.
Explain the theoretical role of theta and gamma oscillations in hippocampal memory encoding, as depicted in the model.
Theta oscillations (slow) structure the temporal framework of memory, segmenting sequences of items across time.
Gamma oscillations (fast) nest within theta cycles, allowing multiple discrete items (e.g. A→D) to be encoded within a single theta cycle.
Each gamma sub-cycle represents a distinct item, enabling serial encoding via phase coding.
This nested architecture supports item separation and temporal ordering, essential for episodic memory.
Physiologically, this aligns with hippocampal field potentials showing gamma bursts nested within theta rhythms during sequential memory tasks.
How does the theta–gamma code provide a neurophysiological basis for short-term memory capacity?
Within each theta cycle (4–10 Hz), multiple gamma cycles (30–80 Hz) occur, each encoding a distinct memory item via synchronous firing of specific pyramidal neuron ensembles.
Empirical estimates suggest ~7 ± 2 gamma cycles per theta wave, matching the classic STM capacity (Ebbinghaus).
Each gamma sub-cycle represents a different network state (e.g., item A–G), enabling sequential activation and temporal ordering.
What physiological evidence links theta oscillations to spatial memory encoding in hippocampal place cells?
As a rat moves through a place field, hippocampal place cells fire at progressively earlier phases of the theta cycle, a phenomenon known as phase precession.
Firing is strongest near the theta trough, corresponding to the centre of the place field.
This shifting phase code allows position to be encoded relative to theta rhythm, creating a temporal code for spatial information.
Because the task is simple and repetitive, noise is low, revealing consistent theta-linked firing patterns.
What is theta phase precession and how does it support spatial memory coding in the hippocampus?
Theta phase precession is the progressive shift in place cell firing to earlier phases of the theta cycle as an animal moves through a place field.
Initially, spikes occur at late (positive) phases; as the animal progresses, spikes advance to earlier phases.
This creates a temporal code for position: the theta phase of firing correlates with spatial location.
It allows the hippocampus to compress sequences of locations into a single theta cycle - supporting spatial and episodic memory encoding.
Demonstrated by O’Keefe & Recce (1993) in rats running linear tracks.
How does theta phase precession across multiple place cells support spatial representation during movement?
As a rat moves through overlapping place fields (e.g., P1 → P5), each place cell fires at a specific location and progressively earlier theta phases.
At any point (e.g., X), several place cells fire simultaneously - strongest from the peak field (e.g., P2), weaker from adjacent fields (e.g., P1, P3).
This overlapping activity forms a population code for location and direction.
The theta phase of each cell’s firing adds a temporal dimension, helping to encode position within a trajectory.
Thus, spatial and temporal information are jointly encoded by hippocampal cell assemblies.
How do theta and gamma rhythms interact to support spatial sequence encoding in the hippocampus?
Place cells fire near the trough of the theta cycle and show phase precession (earlier firing with movement through the field).
Across multiple cells, these theta-timed spikes form ordered sequences representing spatial positions.
Each gamma cycle (~30–80 Hz) within a theta wave (~4–10 Hz) encodes one item (e.g., location A, B, C), creating a temporal sequence of positions.
Overlaying cell activity reveals a compressed representation of past, current and future locations within a single theta cycle.
This theta-gamma code enables animals to maintain an internal spatial map and plan navigational trajectories.
How does theta-phase precession, modulated by gamma rhythms, support spatial prediction and episodic memory formation?
Place cells fire at gamma frequency (~7 ± 2 events) nested within a theta rhythm (4–10 Hz).
Firing is paced by theta:
Past positions are encoded by cells firing at late theta phase, the current position by those firing at the theta trough, future locations by cells firing at early theta phase.
For example, as the animal moves through place field P3, that cell fires:
* First at late theta (coming from P2),
* Then strongest at the trough (P3 centre),
* Then early theta (heading toward P4/P5).
This creates a temporally compressed sequence (past → present → future) within a single theta cycle, with each item encoded in its own gamma sub-cycle.
This structure allows:
* Prediction of upcoming locations.
* Encoding of trajectory and episodic information.
* Integration of space and time within hippocampal circuits.
The system links neural dynamics (theta-gamma coupling) with cognitive capacity (memory, navigation, planning).
How does the Sternberg paradigm provide behavioural evidence for theta-gamma coding in short-term memory?
METHODS:
* Participants are shown a sequence of digits (e.g., 1–6), followed by a delay.
* A probe digit is then presented.
* Task: Decide if the probe was part of the original list.
* Mean reaction time (RT) is recorded for each memory load (1–6 items).
RESULTS:
* RT increases linearly with number of items, regardless of whether the answer is yes or no.
* Slope ≈ 38 ms per item, consistent with ~30 Hz gamma frequency.
* Suggests a serial scanning process: one item compared per gamma cycle (not parallel - searching all at once).
* Theta rhythm paces these gamma comparisons, aligning with hippocampal models of memory encoding.
* Supports the idea that memory retrieval involves gamma-paced serial search, even in humans, where direct recording is limited.
What MEG evidence supports the role of theta and gamma oscillations in short-term memory (STM) during the Sternberg task?
METHODS:
* Human participants performed a Sternberg task (1, 3, 5, or 7 digits).
* A sensory control task used crosses instead of digits.
* MEG recorded cortical activity during the retention interval from 61 locations.
RESULTS:
* Theta power (4-8 Hz) was greater during STM tasks vs. sensory control (digits > crosses).
* Theta power increased with memory load, peaking around 7 items, matching STM capacity.
* Power plateaued when STM load saturated, suggesting a capacity-linked oscillatory mechanism.
* Supports theory that theta paces gamma, with each gamma cycle indexing an item in memory.
* Aligns with behavioural slope from Sternberg (~30 Hz = gamma frequency), indicating serial memory scanning.
How does the strength of theta-gamma coupling influence memory encoding and recall? (High vs Low)
High theta-gamma coupling (TGC):
* Strong gamma activity represents individual items.
* Each item is consistently locked to distinct phases of theta.
* This supports accurate temporal ordering of events (e.g., L → A → K → M).
* Results in good memory encoding and precise recall.
Low TGC:
* Weak gamma activity leads to degraded item representation.
* Poor phase alignment with theta disrupts event ordering.
* Results in inaccurate recall (e.g., scrambled sequence A → L → K → M).
TGC enables theta phase to structure memory temporally, and gamma cycles to encode discrete items.
Without this synchronisation, memory suffers, highlighting the importance of oscillatory coordination in episodic memory.
What does the n-back task reveal about the role of theta-gamma coupling (TGC) in working memory and cognitive decline?
METHODS:
* EEG recorded from 64 channels during 0-, 1-, and 2-back tasks.
* Compared performance across HC, MCI, and AD groups.
* Focused on theta-gamma coupling (TGC) rather than just band power.
RESULTS:
* TGC was the best predictor of 2-back task accuracy, across all clinical groups.
* TGC strength correlated with correct performance (targets > non-targets).
* TGC remained predictive regardless of diagnosis — MCI and AD both showed impaired TGC and reduced accuracy.
* TGC was not predictive in non-ordering tasks, supporting its specific role in temporal working memory.
Conclusion:
TGC reflects dynamic item-order binding in working memory.
Its disruption in MCI/AD highlights its potential as a biomarker for early cognitive decline.
What is procedural memory?
It’s the memory for a behavioural output that we train.
They are not fixed; they continue to be modified by experience and tuned by repetition.
It’s related to how the motor cortex communicates to the striatum and cerebellum.
What are the two major types of procedural memory involving the motor system?
These two types of memory rely on different, but partially overlapping, brain circuits.
- The acquisition of habits and skills
- Sensory-to-motor-adaptations, involving the adaptation of reflexes. (AKA Conditioning).
E.g., Given something light, at the next presentation you will prepare to hold something light.
When it’s actually heavy, at the next presentation you will prepare for something heavy.
What are the two major parts of the motor system involved in procedural memory and what is their role?
Primary Motor Cortex:
- The top level of these motor circuits, critical for the control of force and the flow in muscle movements.
Premotor Cortex:
- Involved in movement preparation and sequencing; co-ordination of muscle on either side of the body
What are the five main brain areas implicated in procedural memory?
Primary Motor Cortex
Premotor Cortex
Supplementary Motor Cortex
Cerebellum
Striatum
What is the cerebellum’s role in procedural memory?
Cerebellum role is to send error message back, monitoring the movement based on the cortical plan, it will communicate the discrepancy due to errors to help correct.
The primary and premotor cortex work with which two main sub-cortical structures? Draw the basic loop to show this.
Striatum (Caudate + putamen)
Cerebellum
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Explain the double dissociation between striatal and hippocampal systems as demonstrated in water maze discrimination tasks.
In water maze experiments, striatal and hippocampal systems show specialised roles in learning:
- Visual discrimination task (colour-based):
Striatal lesions cause severe impairment while hippocampal-lesioned animals perform like controls. - Spatial discrimination task (position-based): Hippocampal/fornix lesions cause severe impairment while striatal-lesioned animals perform like controls.
This double dissociation demonstrates that the striatal system is critical for stimulus-response learning (procedural memory), while the hippocampal system is essential for spatial learning (declarative memory).
What specific deficits do striatal-lesioned animals exhibit in discrimination learning tasks such as the water maze task?
Striatal-lesioned animals show:
* Severe impairment in visual discrimination tasks where learning depends on association between a specific stimulus (colour) and reward
* Persistent high error rates across training trials when discriminating by colour cues
* Intact performance in spatial discrimination tasks where position, not stimulus features, predicts reward
* These deficits reflect the striatum’s crucial role in habit formation and procedural memory acquisition.
Explain the experimental methods and results of the striatal habit system study using water maze discrimination tasks.
METHODS:
* Water maze containing two visually discriminable floating rubber balls
* One ball positioned above large escape platform (+), one above too-small platform (-)
* Visual Discrimination Variant: Position of platforms varied; animals must discriminate by COLOUR
* Spatial Discrimination Variant: Escape platform position constant; colours varied randomly
* Three experimental groups: control, striatal lesion and fornix/hippocampal lesion animals
RESULTS:
* Visual Discrimination (colour-based): Striatal-lesioned animals showed persistent impairment (high error rates) across all trial blocks; control and hippocampal groups improved steadily
* Spatial Discrimination (position-based): Hippocampal/fornix-lesioned animals showed severe impairment; control and striatal groups learned effectively
* Double dissociation demonstrated between striatal (stimulus-response) and hippocampal (spatial) learning systems
What were the specific methods and results of the Visual Discrimination Variant in the striatal habit system experiment?
METHODS:
* Water maze with two differently colored floating balls
* Position of platforms varied across trials
* Animals required to discriminate by COLOUR to find escape platform
* Success required learning stimulus-response association (colour → escape)
* Performance measured by mean number of errors across 15 trial blocks
RESULTS:
* Control animals: Showed steady learning curve with decreasing errors
* Fornix/hippocampal animals: Performed similarly to controls
* Striatal-lesioned animals: Showed severe impairment with consistently high error rates
* By final trials, ~4-error difference between striatal and other groups
* Demonstrated striatum’s critical role in non-spatial, cue-based learning
Describe the methods and results of the Spatial Discrimination Variant in the striatal habit system water maze study.
METHODS:
* Water maze with two floating balls of different colors
* Escape platform position remained constant across trials
* Colour of balls varied (no longer associated with escape)
* Animals required to discriminate by POSITION to find escape
* Performance measured across 7 trial blocks
RESULTS:
* Control animals: Showed effective learning with errors decreasing to near-zero
* Striatal-lesioned animals: Performed similarly to controls, reaching low error rates
* Fornix/hippocampal animals: Showed persistent impairment with higher error rates
* By final trials, ~3-error difference between hippocampal and other groups
* Confirmed hippocampus/fornix is essential for spatial learning independent of visual cues
Explain the experimental design and findings of Cook & Kesner’s (1988) study on the striatal habit system using the TRAIN → LESION → TEST paradigm.
METHODS:
* Rats trained on both place tasks and response tasks until proficient
* Striatal (caudate) lesions performed after training
* Testing conducted post-lesion to assess retention
* Place tasks: standard 8-arm radial maze and place memory task
* Response tasks: “turn right into adjacent arm” and right-left discrimination (“take left arm of two available”)
* Performance measured pre-lesion and post-lesion
RESULTS:
* Place tasks: Normal performance maintained after striatal lesions (~80% correct)
* Response tasks: Performance dropped to chance level after lesions (~30-40% correct)
* Double dissociation demonstrated between intact spatial memory and impaired procedural/habit memory
* Confirmed striatum’s selective role in response learning but not spatial learning
What specific deficits were observed in the response tasks following striatal lesions in the Cook & Kesner (1988) study?
METHODS:
* Two response tasks tested:
* “Turn right into adjacent arm” task requiring egocentric response
* Right-left discrimination task (“take left arm of two available”)
* Pre-lesion performance at ~100% correct
* Post-lesion performance compared to chance level
RESULTS:
* Post-lesion performance dropped to chance level (~30-40% correct)
* Adjacent arm task: Rats unable to consistently execute the learned “turn right” response
* Right-left discrimination: Rats unable to maintain the learned habit of selecting left arm
* Demonstrated striatum’s critical role in procedural memory and stimulus-response associations
* Indicated that striatal lesions specifically impair habitual behaviors rather than spatial navigation
Describe the experimental methods and results of Kermadi & Joseph’s (1995) study on response sequencing and the striatum.
METHODS:
* Monkeys trained to fixate central point, then follow sequence of three dots (L, R, or U positions)
* Animals required to fixate each location in presentation order before reaching to target
* Six different sequence combinations tested (LUR, RLU, URL, LRU, ULR, RUL)
* Single-unit recordings from striatal neurons during task performance
RESULTS:
* Striatal neurons showed sequence-specific activation patterns
* Neurons responded to particular locations only within specific sequence contexts
* Example: Neuron fired strongly for “L” position only in ULR pattern, not in other sequences
* Demonstrated context-dependent coding where neural response depends on sequence position
* Supported striatum’s role in encoding procedural aspects of sequential motor behaviors
What is context-dependent coding in the striatum and why is it significant for understanding procedural memory?
Context-dependent coding refers to striatal neurons that respond to specific actions only when they occur within particular sequential contexts. In Kermadi & Joseph’s study, neurons fired for a location (e.g., “L”) only when it appeared in a specific sequence (e.g., ULR).
This property is significant because it:
* Explains how the striatum encodes complex action sequences, not just individual movements
* Provides neural basis for procedural memory’s sequence-specific nature
* Demonstrates how habits become “chunked” into integrated behavioral units
* Explains why striatal damage impairs sequence learning while preserving individual movements
* Reveals how the brain transitions from conscious sequence execution to automatic performance
Compare and contrast the roles of the striatum in the three followingexperimental paradigms: water maze discrimination, 8-arm radial maze and sequence learning tasks.
Water Maze Discrimination:
* Striatum essential for visual/cue-based discrimination (colour → reward)
* Striatal lesions impair stimulus-response learning but spare spatial learning
* Demonstrates striatum’s role in simple associative learning
8-Arm Radial Maze (Cook & Kesner):
* Striatal lesions impair response tasks (“turn right,” “choose left arm”)
* Spatial navigation remains intact after striatal lesions
* Shows striatum’s role in egocentric response learning
Sequence Learning (Kermadi & Joseph):
* Striatal neurons encode actions in sequence-specific contexts
* Neurons respond to locations only within particular sequences
* Reveals striatum’s role in complex procedural learning and action sequencing
All paradigms demonstrate striatum’s critical role in procedural/habit learning while confirming its non-involvement in spatial/declarative memory.
Explain the functional organisation of the striatum in procedural learning and how it supports the transition from deliberate to automatic behaviors.
The striatum facilitates procedural learning through:
* Initial encoding of stimulus-response associations in dorsomedial striatum
* Gradual shift to dorsolateral striatum as behaviors become habitual
* Context-dependent neuronal firing that encodes specific action sequences
* Integration with cortical inputs to form stable motor programs
* Dopaminergic reinforcement that strengthens successful action patterns
This organisation enables the transition from conscious, goal-directed actions to automatic, efficient habits, allowing complex behaviours to be executed with minimal cognitive load.
What does the double dissociation between striatal and hippocampal systems reveal about multiple memory systems in the brain? (7)
The double dissociation reveals:
* Brain contains parallel, specialised learning systems that operate simultaneously
* Striatal system: Processes stimulus-response associations and procedural sequences
* Hippocampal system: Processes spatial relationships and declarative knowledge
* Systems can compete or cooperate depending on task demands
* Damage to one system may unmask the operation of the other
* Evolution has preserved these distinct systems because they serve complementary functions in learning
* Explains why certain memory functions remain intact after brain damage while others are impaired
How do the neurophysiological properties of striatal neurons support their role in sequence learning?
Striatal neurons support sequence learning through:
* Pattern-specific firing that responds to actions only in specific sequential contexts
* Integration of cortical inputs from motor, sensory and prefrontal regions
* Medium spiny neurons that require coordinated input to become active
* Synaptic plasticity that strengthens connections between neurons representing sequential actions
* Lateral inhibition that suppresses competing motor programs
* Sustained activity patterns that bridge temporal gaps between sequence elements
* Dopamine-mediated reinforcement that stabilizes successful action chains
These properties create a neural substrate for encoding complex procedural memories as unified action sequences.
Draw a picture of the anatomical connectivity of the striatul subsystem.
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Describe the anatomical connectivity of the striatal subsystem.
The striatum receives projections from the entire cortex.
It has minimal projections to the brainstem and none to the spinal cord.
The striatum primarily projects to the thalamus.
The thalamus then projects to premotor, motor and prefrontal cortex.
This forms a cortex → striatum → thalamus → cortex loop.
This connectivity allows integration of diverse information without direct motor control.
Why is the striatum’s “indirect motor output” significant for procedural memory?
The striatum lacks direct projections to the spinal cord.
It influences movement selection through the thalamo-cortical pathway.
This indirect control allows modulation of which actions are selected.
The architecture explains why striatal damage impairs action selection but not basic movement.
It enables the striatum to function as a “gatekeeper” for learned procedural responses.
How does striatal circuit architecture support habit formation?
The striatum receives input from the entire cortex, enabling context-action associations.
The striatum-thalamus-cortex loop creates a circuit strengthened through repetition.
Limited output pathways force selection between competing actions.
The loop architecture allows learned sequences to trigger automatically.
This organisation enables complex behaviors to execute without conscious control.
Describe the T-maze learning experiment design used to study striatal output neurons.
METHODS:
* Rats trained to run T-maze for food reinforcement
* Auditory cues (click/tone) signaled turn direction
* Four learning stages with 40 trials per session:
* Acquisition (sessions 1-5): learn to 72% correct
* Overtraining (sessions 6-15): strengthen habit
* Extinction (sessions 16-22): no/little reinforcement
* Reacquisition (sessions 23-28): reinforcement restored
* Striatal neural activity recorded throughout
RESULTS:
* Performance improved during acquisition/overtraining (80-85% correct)
* Performance dropped during extinction (to near 0%)
* Rapid recovery during reacquisition (to 90%+)
* Running time decreased with learning, increased during extinction
* Trial duration showed similar pattern
How does striatal activity change across different stages of procedural learning in the T-maze task?
Striatal neurons show distinct activity patterns across learning stages.
During acquisition, neural activity gradually increases as associations form.
In overtraining, activity stabilises as the behaviour becomes habitual.
During extinction, striatal activity patterns become disrupted.
Reacquisition shows rapid restoration of striatal firing patterns.
The striatum encodes the relationship between cues and appropriate motor responses.
This pattern demonstrates the striatum’s role in forming and maintaining procedural memories.
What does the extinction-reacquisition pattern in the T-maze experiment reveal about the nature of striatal-dependent procedural memory?
Extinction causes performance to drop dramatically (near 0% correct).
Running time increases substantially during extinction.
Despite performance loss, reacquisition occurs rapidly.
This rapid reacquisition suggests procedural memories remain stored during extinction.
The striatum maintains the learned associations even when not expressed.
This differs from declarative memory which shows gradual relearning curves.
The pattern demonstrates that habits, once formed, are difficult to erase completely.
Procedural memory shows “savings” - faster relearning than original acquisition.
Describe the neural encoding patterns in striatal neurons during T-maze learning as shown in Barnes et al. (2005).
METHODS:
* Researchers recorded striatal neuron activity across T-maze task phases
* Neural activity visualized as heat map (red/orange = high firing, blue = low firing)
* Activity measured during overtraining (session 11) and extinction (session 23)
RESULTS:
* Striatal neurons show phase-specific activation patterns during task execution
* Strongest activity (red/orange clusters) occurs during turn onset/offset phases
* Neural activity patterns correlate directly with behavioural performance
* Spike proportion increases during acquisition/overtraining, decreases in extinction
* Warning cue neural response strongly predicts both accuracy and speed
* Different task components are encoded by specific striatal neuron populations
What is the significance of the warning cue response in striatal neurons during procedural learning? (T-maze learning as shown in Barnes et al., 2005)
The warning cue response in striatal neurons serves as a critical predictor of performance.
Higher neural activity during warning cue strongly correlates with percentage correct (r ≈ 0.8).
Warning cue response negatively correlates with running time (stronger signal = faster performance).
This preparatory activity represents the activation of the learned procedural memory.
The warning cue response demonstrates how the striatum initiates learned action sequences.
This early neural activity provides evidence for the striatum’s role in action preparation.
The correlation with performance metrics confirms the functional significance of this neural encoding.
How do the neural activity patterns in the striatum change across different learning stages in the T-maze task?
Striatal neural activity shows systematic changes across learning stages.
During acquisition, spike proportion gradually increases as the task is learned.
In overtraining, activity reaches peak levels with strongest encoding during turn execution.
During extinction, neural activity patterns significantly decrease, particularly in turn-related phases.
In reacquisition, activity patterns rapidly recover to levels similar to overtraining.
These changes directly parallel behavioral performance metrics.
The pattern demonstrates how procedural memories are encoded, suppressed, and reactivated in striatal circuits.
The rapid recovery during reacquisition provides neural evidence for the persistence of procedural memories.
Explain how ensemble firing patterns in striatal output neurones evolve across acquisition, extinction and re‑acquisition in a rat T‑maze.
- During acquisition, novel task‑related ensembles form and stabilise.
- In extinction, these patterns reverse and then re‑emerge.
- On re‑acquisition, the original ensembles are reinstated—changes tightly track behavioural performance.
Describe how task‑irrelevant firing in striatal output neurones is modulated across acquisition, extinction and re‑acquisition phases of T‑maze learning.
- Acquisition: non‑task‑related spikes are actively suppressed.
- Extinction: these irrelevant spikes rebound.
- Re‑acquisition: suppression of irrelevant firing resumes alongside task‑relevant pattern reinstatement.
Explain what phase‑dependent shifts in ensemble codes within cortico‑basal ganglia circuits represent in the context of habit formation.
They are the neural equivalents of habit learning: specific, task‑phase‑locked ensembles in cortex→striatum→substantia nigra pathways encode automated response strategies.
Outline how control of T‑maze performance transitions from hippocampal to striatal systems, emphasising the specificity of striatal neuron involvement.
Early trials depend on hippocampal spatial mapping; with training, control transfers to the dorsolateral striatum, where select output neurone ensembles (not global striatal activation) encode the habitual turn‑response.
Explain why the striatum is not considered a direct controller of motor output.
Anatomically, the striatum sends no direct projections to spinal motor neurones; instead, it projects to pallidal and nigral output nuclei, modulating thalamo‑cortical circuits rather than driving muscles itself.
Detail how striatal connections with premotor and primary motor cortices inform its role in motor function.
Reciprocal links between striatum and motor/premotor cortices support the planning, sequencing and initiation of complex movement patterns, by selecting and reinforcing cortical motor programmes.
Describe how striatal inputs from limbic and prefrontal regions underpin its involvement in goal‑oriented behaviour.
Afferents from the amygdala convey motivational/emotional salience, while PFC inputs provide executive planning; integration within the striatum enables action selection aligned with reward expectations and behavioural goals.
Draw a picture of the anatomical structure of the cerebella subsystem in procedural learning.
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In the cerebellar motor subsystem, which major afferent and efferent pathways enable it to monitor and influence movement?
- Afferents: direct proprioceptive input from the spinal cord plus bi‑directional connections with brainstem nuclei (vestibular, reticular, red nuclei) and descending “efference copy” from motor cortex.
- Efferents: cerebello‑thalamo‑cortical projections (smaller in magnitude than striatal outputs) to premotor and primary motor cortices for adjusting motor commands.
Explain how the cerebellum computes and corrects motor errors during movement.
- Receives intended movement plan (from motor cortex) and actual sensory feedback (spinal/brainstem).
- Integrates these to detect discrepancies (prediction vs. outcome).
- Sends corrective signals via the thalamus back to motor/premotor cortex to refine ongoing and future motor commands.
How do the cerebellum’s connections with brainstem nuclei facilitate rapid sensorimotor control?
Bi‑directional loops with brainstem (e.g. vestibular, reticular) link spinal reflex arcs and cerebellar computation, allowing immediate modulation of muscle tone and posture in response to changing sensory inputs.
Contrast the cerebellar and striatal systems in terms of projection strength and functional emphasis in motor control.
- Projection strength: cerebellar outputs to cortex are comparatively small; striatal outputs are more extensive.
- Function: cerebellum specialises in real‑time error correction and sensorimotor integration; striatum underpins goal‑directed action selection and habitual sequence encoding.
What does the circuitry of the cerebellum suggest about it’s role in procedural memory compared to the striatum?
This region has much stronger connections with the brain stem and spinal cord and much weaker connections to the cortex than the striatal circuit.
This suggest that it’s circuitry may be more involved in execution of movements and the acquisition of conditioned reflexes.
In rabbit Pavlovian eyeblink conditioning, what are the conditioned stimulus (CS), unconditioned stimulus (US), unconditioned response (UR) and conditioned response (CR)?
CS: Tone or light lasting 250–1000ms
US: Corneal air‑puff to the eyelid
UR: Reflexive eyeblink to the air‑puff
CR: Learned eyeblink in response to the CS alone after several CS–US pairings
What lesion and molecular‑block experiments demonstrate that the interpositus nucleus is essential for CR acquisition but not UR production?
Interpositus lesion or protein synthesis blockade within it prevents animals ever acquiring a CR
Neither manipulation alters the reflexive UR, proving interpositus is critical for learning but not for basic blink circuitry
How do reversible inactivations of the red nucleus reveal a dissociation between learning and performance of the eyeblink CR?
During training: inactivating red nucleus or its projection from interpositus blocks CR expression
On recovery: CRs emerge immediately at their learned magnitude, showing learning occurred “offline” even though performance was suppressed during inactivation
Summarise the methods and results of the rabbit eyeblink conditioning study investigating cerebellar learning.
METHODS:
* Paired a tone/light CS (250–1000ms) with a corneal air‑puff US in rabbits, measuring reflexive UR and learned CR.
* Lesioned or blocked protein synthesis in the interpositus nucleus to test acquisition.
* Reversibly inactivated the red nucleus (and its projection from interpositus) during training to dissociate learning versus performance.
RESULTS:
* Interpositus lesions or protein synthesis blockade abolished CR acquisition but left the UR intact.
* Red‑nucleus inactivation prevented CR expression during training, yet on recovery rabbits immediately expressed CRs at full strength, demonstrating that learning was stored in the interpositus nucleus independent of real‑time output.
Provide a basic definition of emotions.
A wide range of observable behaviours, expressed feelings and changes in body state.
What are the four aspects of emotion?
- Feelings
- Actions
- Physiological Arousal (e.g., autonomic arousal)
- Motivational Programs (adaptive programs that solve problems)
What are the 8 basic emotions as discerned by Plutchik (1994)?
Joy/Sadness
Affection/Disgust
Anger/Fear
Expectation/Surprise
Define the limbic system and its primary functions.
A set of interconnected subcortical and cortical structures (centred on the hypothalamus) that mediate emotion, stress responses, mood regulation and reward/addiction processes.
Outline the components and pathway of Papez’s Limbic system circuit.
Hippocampus → fornix → mammillary bodies → mammillothalamic tract → anterior thalamic nuclei → cingulate cortex → entorhinal cortex → hippocampus; proposed to underlie emotional expression.
Explain MacLean’s expansion of the limbic system.
Inclusion of amygdala, septal area, nucleus accumbens and portions of prefrontal cortex, forming the “paleomammalian” brain layer for integrating emotion with cognition and drive.
Describe the Triune Brain model and the evolutionary role of the limbic system.
Brain comprises: reptilian (brainstem/basal ganglia), paleomammalian (limbic), neomammalian (neocortex); limbic system evolved to add emotional and motivational regulation atop primitive motor/drive circuits.
- Debunked as it’s based on birds; it’s a vast underestimation of what birds and lizards can do, it’s largely false.
Why is the limbic system a key target for psychotropic drugs and which neurotransmitters are most implicated?
Its central role in emotion, stress and reward makes it vulnerable in mood and psychotic disorders; therapeutics modulate noradrenaline, dopamine and serotonin transmission within limbic circuits.
Explain how neocortical and limbic‑system volumes differ across rabbit, cat and monkey brains and the functional implication of this divergence.
Morphology:
* From rabbit→cat→monkey, neocortex shows progressive gyrencephaly (degree of cortical folding) and relative expansion, whereas limbic structures stay proportionally constant.
Implication:
* Advanced mammals possess greater neocortical real‑estate for high‑order processing (e.g. context, planning), while phylogenetically older limbic circuits continue to mediate conserved emotional drives.
Why might humans exhibit superior emotional regulation compared to less‑developed mammals?
Expanded neocortex, particularly prefrontal regions, sends descending projections to amygdala, hypothalamus and brainstem, exerting top‑down inhibitory control over limbic‑driven responses and facilitating deliberate reappraisal.
Distinguish “classically conditioned” emotional responses from “cognitive appraisal” in terms of neural substrates.
- Classical conditioning:
Automatic affective reactions (e.g. fear, pleasure) acquired via subcortical loops (Papez/MacLean circuits) in the limbic system. - Cognitive appraisal:
Context‑sensitive evaluation and regulation of the same stimuli by neocortical networks (especially prefrontal cortex), enabling flexible, goal‑directed emotional control.
What did Cannon & Britton (1925) discover in cats and dogs about decortication?
They removed the cortex in cats and dogs which produced an aggressive reaction (sham rage) to routine handling.
Suggests that the cortex controls (inhbits) the expression of emotional responses.
What did Bard (1928) discover in regards to decoritcation?
Following the discovery of decortication rage when cortex was removed, he went on to show that subcortical sites (particularly the hypothalamus) are particularly important in emotions such as sham rage.
Describe the sequence of neural pathways comprising the Papez circuit and its role in emotional processing.
Sensory input → thalamus
“Stream of feeling”: thalamus → hypothalamus (mammillary bodies) → anterior thalamic nuclei via mammillothalamic tract
“Brain reaction”: anterior thalamus → cingulate gyrus → sensory neocortex (produces conscious feeling)
“Stream of thought”: cingulate → hippocampus via cingulum → hypothalamus via fornix
Autonomic output: hypothalamus → brainstem/spinal autonomic centres → physiological expression (mood)
Draw the Papez circuit for Emotional Processing
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Which nodes of the Papez circuit mediate conscious emotional feeling versus physiological expression and what is the unresolved debate about their timing?
Feeling (“brain reaction”): cingulate gyrus and associated neocortical areas
Physiological expression (“body reaction”): hypothalamus via autonomic outputs from thalamus
Debate: whether bodily changes (autonomic arousal) precede and generate conscious feeling (James–Lange), or vice versa (Cannon–Bard)
What inputs trigger activation of the Papez circuit and how do they integrate to produce emotional states?
Sensory afferents (e.g. visual, auditory) arrive at thalamus for rapid arousal
Memory/contextual inputs to cingulate/hippocampus supply past experience
Integration within the loop links external stimuli with past emotional associations, coordinating feeling (cingulate) and physiological response (hypothalamus) into a coherent mood.
Give 4 critiques of the concept of the “limbic system” as a discrete, dedicated emotional network.
- Anatomical vagueness: Includes heterogeneous nuclei (hippocampus, amygdala, septum, PFC) with diverse functions beyond emotion.
- Overlap with other systems: Many so‑called limbic regions participate in memory, attention, motor control and cognition.
- Distributed dynamics: Emotional states arise from temporally coordinated activity across multiple large‑scale circuits (cortical and subcortical), not a single “on/off” limbic toggle.
- Whole‑brain integration: Modern imaging and connectivity studies show emotion emerges from network interactions spanning neocortex, basal ganglia, cerebellum and brainstem as well as traditional limbic nodes.
Outline MacLean’s limbic‑system theory, specifying its components and proposed function.
Components:
* Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex)
* Broca’s limbic lobe (pyriform & rhinal cortices)
* Septum & portions of basal ganglia
* Amygdala, ventromedial PFC & orbitofrontal cortex (later additions)
Function: Integrates visceral (internal) states with sensory inputs to generate adaptive visceromotor and affective responses—i.e. the “visceral brain” for emotion and drive.
Outline the evolutionary significance and sensory role of the olfactory system in mammals.
- Provides the sole direct sensory input to allocortex (olfactory cortex) without thalamic relay.
- Phylogenetically the oldest major sense, especially pronounced in macrosmatic mammals for detecting environmental cues.
Describe the anatomical location and core functions of the amygdala.
- A collection of nuclei in the anterior temporal lobes, continuous with the caudate.
- Electrical stimulation elicits fear and rage in animals.
- Integrates with cingulate cortex to mediate emotional valence and emotional memory consolidation.
Explain the role of the hippocampus in memory and its interaction with the amygdala.
- Critical for autobiographical (episodic) and contextual memory.
- Encodes the context in which fearful or emotional events occur, providing situational framework for amygdala‑driven fear responses.
Detail how the hypothalamus links emotional states to autonomic and endocrine outputs.
- Coordinates autonomic responses (e.g. sympathetic activation during fear) via descending projections to brainstem and spinal centres.
- Regulates endocrine systems through pituitary control (e.g. stress hormone release), integrating emotional and physiological homeostasis.
Where is the amygdala located and which neighbouring limbic structures surround it?
The amygdala sits in the anterior medial temporal lobe, immediately above the parahippocampal gyrus and adjacent to the hippocampus.
It lies ventral to the anterior nucleus of the thalamus and cingulate gyrus, and rostral to the mammillary bodies, with the fornix arching just above it.
Outline the main afferent and efferent pathways of the amygdala in the limbic system.
Afferents:
* Olfactory bulb via lateral olfactory tract
* Sensory thalamus (via dorsomedial nucleus) and sensory cortices (e.g. temporal areas)
* Hippocampus/parahippocampal gyrus (contextual input)
Efferents:
* Stria terminalis → hypothalamus (mammillary bodies) & septal nuclei
* Ventral amygdalofugal pathway → basal forebrain nuclei, anterior thalamus, and cingulate gyrus
* Outputs to brainstem autonomic centres for emotional‐behavioural responses
What are the three major divisions in the Amygdala and what are their overall information flow?
Lateral nucleus (L): main sensory‑integration hub, receives thalamic & cortical inputs.
Basal nuclei (B; including basolateral & basomedial complexes): further integrate L outputs, modulate reward/emotional valence.
Centro‑medial nuclei (C‑M): final output stage projecting to hypothalamus, brainstem and striatum to drive autonomic and behavioural responses.
Detail the principal functions of the lateral nucleus of the amygdala in emotional learning.
Site of CS–US plasticity in fear conditioning (tone/light ↔ shock).
Receives rapid “low road” thalamic input for coarse threat detection and “high road” cortical input for detailed evaluation.
Sends processed signals to basal and C‑M nuclei and to hippocampus for contextual modulation.
Contrast the roles of the basolateral versus basomedial subdivisions of the basal amygdala.
Basolateral nucleus (BLa/BLp): promotes reward‑seeking, suppresses social approach and can be anxiogenic; projects to nucleus accumbens and PFC.
Basomedial nucleus: exerts anxiolytic influence, regulating stress resilience via connections back to hippocampus and hypothalamus.
Explain how the centro‑medial nuclei of the amygdala generate emotional responses.
- Receive convergent input from lateral & basal nuclei.
- Project to hypothalamic (autonomic/endocrine) and brainstem motor centres to produce fear‑related arousal (↑heart rate, sweating, freezing) and hormonal release.
Summarise the methods and results of the macaque basolateral amygdala single‑neuron study on conspecific social signals.
METHODS:
* Extracellular single‑unit recordings from basolateral amygdala in awake macaques.
* Presented photographs of four familiar monkeys each displaying three facial expressions (appeasement/lip‑smack, neutral, threat).
* Collected peristimulus time rasters and firing‑rate histograms for each identity–expression combination.
RESULTS:
* Many neurons (≈64%) exhibited non‑linear tuning: their firing depended on a specific identity‑expression pairing, not on expression or identity alone.
* Examples included cells that responded most to appeasement in one monkey but not to threat or neutral, and others preferring threat > neutral > appeasement.
* Demonstrates basolateral amygdala encodes high‑order, context‑dependent social signals rather than simple feature detection.
Outline the principal afferent routes by which a threatening stimulus reaches the amygdala in the fear memory system.
“Low‑road” thalamic route: Sensory organ → sensory thalamus → lateral nucleus of amygdala (rapid, coarse)
“High‑road” cortical route: Sensory organ → sensory cortex → lateral nucleus (detailed, slow)
Contextual inputs: Hippocampus → basal and lateral nuclei (provides spatial/episodic context)
Explain how the hippocampus modulates amygdala‑dependent fear conditioning.
The hippocampus encodes the environmental context of an aversive event and sends this information to the amygdala’s lateral and basal nuclei.
This contextual signal allows the amygdala to generate fear responses selectively in the original conditioning environment.
Describe the major efferent pathways from the central nucleus of the amygdala that produce emotional (fear) responses.
Central grey (periaqueductal grey): orchestrates defensive behaviours (freezing, fight/flight)
Lateral hypothalamus: triggers autonomic outputs (↑heart rate, blood pressure, respiration)
Bed nucleus of the stria terminalis: drives neuroendocrine hormone release (stress hormones via HPA axis)
Detail the sequence of information flow in the emotional (fear) memory system from sensory detection to behavioural output.
Detection: Threat → sensory organ
Relay: → thalamus (“low road”) and → sensory cortex (“high road”)
Integration: → amygdala (lateral → basal/accessory basal → central nucleus), with contextual gating by hippocampus
Output: central nucleus → brainstem/autonomic/endocrine centres → coordinated emotional behaviour, autonomic arousal and hormonal responses.
Draw an Image of the Brain system for emotional memory in a rat pavlovian conditioning experiment.
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Outline the dual afferent routes conveying the CS (tone) and US (footshock) to the lateral amygdala (LA) in auditory fear conditioning and the efferent pathways from the central nucleus (CE) that generate fear responses.
CS → LA:
* Thalamic “low road”: auditory thalamus → LA (fast, coarse)
* Cortical “high road”: auditory cortex → LA (slower, detailed)
US → LA:
* Thalamic: somatosensory thalamus → LA
* Cortical: somatosensory cortex → LA
LA → CE: integration of CS–US associations
CE outputs:
* Central grey (periaqueductal grey): freezing
* Lateral hypothalamus: blood‐pressure increase
* Paraventricular nucleus (PVN) of hypothalamus: stress‐hormone release
Why are direct thalamic projections to the lateral amygdala (“low road”) essential for survival‑critical fear responses?
They provide a rapid, subcortical shortcut for coarse sensory information to reach the amygdala, enabling immediate defensive reactions before slower cortical processing refines stimulus evaluation.
Summarise the methods and results of LeDoux’s lesion study in Pavlovian fear conditioning.
METHODS:
* Conditioning: Paired an auditory CS (tone) with a footshock US in one environment.
* Testing: Measured freezing to (a) the original context and (b) the tone in a novel context.
* Lesions: Bilateral lesions of amygdala (lateral/central nuclei), hippocampus or dorsal striatum.
RESULTS:
* Amygdala lesions: abolished freezing to both context and tone (disrupts Pavlovian and contextual conditioning).
* Hippocampal lesions: selectively eliminated contextual freezing but left tone‑elicited freezing intact.
* Striatal lesions: had no effect on either form of fear conditioning.
Summarise the methods and results of rat lateral amygdala recordings during fear conditioning, differential conditioning and extinction.
METHODS:
Subjects: Rats implanted with tetrodes in lateral amygdala (LA).
Procedures:
* Baseline: 10 tone CS presentations (no US).
* Conditioning: 10 tone CS–footshock US pairings.
* Controls: unpaired CS/US (to test necessity of pairing).
* Differential conditioning: interleaved CS⁺ (paired) vs CS⁻ (unpaired).
* Extinction: repeated CS alone.
Measurements: peristimulus spike rasters & firing‐rate histograms for each trial block.
RESULTS:
* Conditioning: All recorded LA neurons showed a marked increase (>200%) in CS‐evoked firing after CS–US pairing (Quirk etal.,1997).
* Unpaired control: No change in CS responses when CS and US were unpaired (Quirk etal.,1995).
* Differential: CS⁺ responses potentiated; CS⁻ responses actually depressed below baseline.
* Extinction: CS‐elicited firing declined in concert with behavioural extinction, indicating a new inhibitory memory trace (CS≠US) that suppresses but does not erase the original CS→US association.
How do lateral amygdala (LA) neurons change their firing to a tone CS before and after paired CS–US fear conditioning, and what control demonstrates the necessity of pairing?
Before conditioning: LA neurons show minimal or inconsistent tone‐evoked spiking.
After paired CS–US conditioning: All recorded LA units exhibit a robust increase in tone‐evoked firing (>200% of baseline) across 10 CS–US pairings (Quirk etal.,1997).
Control (unpaired CS/US): When tone and shock are presented unpaired, LA responses to the tone do not change, proving that CS–US contingency is required for synaptic plasticity.
Describe how LA firing encodes fear memory independently of freezing behaviour.
Novel context or CS-: LA neurons do not increase firing to a novel tone or in a familiar tone presented in a non‑shock context, mirroring absence of freezing.
CS⁺ with CE inactivation: Infusing lidocaine into central nucleus (CE) blocks freezing but does not prevent the conditioned increase in LA firing to CS⁺.
Conclusion: LA stores the CS→US memory trace; behavioural output (freezing) is downstream in CE.
What changes occur in LA neurons during differential conditioning with CS⁺ versus CS⁻ tones?
CS⁺ (paired): Tone‐evoked LA firing potentiates markedly.
CS⁻ (unpaired): Tone‐evoked firing actually depresses below pre‐training baseline.
Implication: LA circuits can encode positive (potentiation) and negative (depression) valence based on CS–US contingency.
How do LA neuron responses change across extinction trials and what does this reveal about the nature of extinction?
During extinction (CS alone): CS‐evoked LA firing gradually declines in parallel with reductions in freezing.
Memory trace: Original CS→US potentiation is not erased but inhibited - LA units remain capable of firing if inhibition is lifted.
Inference: Extinction forms a new inhibitory memory (CS≠US) rather than unlearning the original association.
Which prefrontal pathway mediates inhibition of LA during extinction, and how does this support extinction memory?
Infralimbic (IL) PFC→LA projections: IL activation during extinction drives GABAergic interneurons in LA, suppressing CS‐evoked firing.
Functional role: This top‑down inhibition gates the expression of the original fear memory without erasing it, enabling context‑dependent retrieval of extinction.
Summarise the methods and results of the vmPFC‑lesion study on recall of fear extinction (Quirk etal., 2000).
METHODS:
* Rats underwent tone–shock conditioning (Day1), followed by extinction training (tone alone) later that day.
* On Day2, before testing, half received bilateral ventromedial PFC (vmPFC) lesions; controls had sham surgery.
* Measured freezing to the tone during Day2 recall.
RESULTS:
* Conditioning & extinction (Day1): vmPFC‑lesioned and sham groups froze similarly during tone–shock pairing and showed equivalent extinction.
* Recall (Day2): Sham rats exhibited low freezing (extinction recall), whereas vmPFC‑lesioned rats showed high freezing—failure to recall extinction.
* Conclusion: vmPFC is not required for initial extinction learning but is essential for retrieval of the extinction memory.
Summarise the methods and results of infralimbic‑PFC recordings during extinction recall (Milad & Quirk, 2002).
METHODS:
* Rats implanted with electrodes in infralimbic (IL) cortex.
* Underwent tone–shock conditioning, extinction training (tone alone) on Day1, and extinction recall (tone alone) on Day2.
* Recorded IL neuronal firing and measured freezing.
RESULTS:
* Extinction recall (Day2): A subpopulation of IL neurons showed a significant increase in tone‑evoked firing only during recall, coinciding with reduced freezing.
* Interpretation: IL neuronal activity signals the retrieval of extinction memory and likely exerts top‑down inhibition over amygdala to suppress fear responses.
* Clinical note: Impaired IL activation during extinction recall is implicated in PTSD and anxiety disorders.
Who first defined episodic memory and what was it’s human definition?
Tulving (1983, 2002) as being a memory specific to humans that receives and stores information about temporally dated episodes or events and the temporal-spatial relationships between them.
What are the basic ‘parameters’ that you can use to define episodic memory?
It’s memory for ‘what’, ‘where’ and ‘when’, learnt in a single ‘trial’ requiring no ‘training’.
It includes the ability to plan for future events (mental time travel).
Summarise the methods and results of Clayton etal.’s scrub‐jay “what–where–when” episodic‐like memory experiment.
METHODS:
* Birds learned that wax worms perish 124h after caching, whereas peanuts remain fresh.
* Caching1: Each jay cached either peanuts or worms on one half of a tray for 4h.
* Caching2 (120h later): Jays cached the other food type on the opposite tray half.
* Retrieval test (after removing food): Presented empty tray with fresh sand at either 4h or 124h post‑worm caching.
* Controls: (a) Jays never taught worm decay (tested at 4h vs 124h); (b) decay timing reversed.
RESULTS:
* At 4h, jays preferentially inspected/recached worm sites (worms still edible).
* At 124h, jays ignored worm sites and inspected peanut sites instead (worms decayed).
* In untaught controls, jays inspected worm sites equally at both intervals, ruling out simple forgetting.
* Conclusion: Jays remember what was cached, where, and when, meeting Tulving’s episodic‐memory criteria.
Summarise the methods and results of Clayton etal.’s scrub‐jay “mental time travel” (future planning) experiment.
METHODS:
* Over 6days, jays experienced a rotating schedule:
* “Breakfast compartment” (A or C) delivered food in the morning; the other compartment was empty.
* Each location alternated daily in a counterbalanced order.
* On Day7, jays were sated, then given pine nuts and access to both compartments (no food bowls).
* Measured where jays chose to cache nuts (anticipating next‑day breakfast).
RESULTS:
* Jays cached significantly more nuts in the compartment that had been empty at that time of day during training.
* Demonstrates planning for a future state (hunger) by choosing a location where food would be needed.
* Caveat: Repeated training introduces associative reinforcement; without verbal report, true “episodic” or “mental time‐travel” interpretations remain debated.
Define episodic memory according to Tulving’s WWWWhen framework and explain why the “when” component is problematic in animal studies.
WWWWhen: Episodic memory requires encoding What happened, Where, and When (Tulving).
Animal issue: “When” (temporal order or elapsed time) is hard to demonstrate non‑verbally and often confounded by circadian or age cues.
Explain how the “when” component of episodic memory can be replaced and by what in non‑verbal tasks.
WWWWhich: Substitutes “when” with identification of the experience context (“which occasion”/which session).
Eacott & Easton (2010): Rats can remember which of two encoding episodes an object–location event occurred, demonstrating a contextual, single‑trial memory dependent on hippocampus.
What 4 essential criteria should a WWWWhich episodic‑like memory task in rodents meet?
Incidental encoding: Animals aren’t reinforced or trained to memorize; memory forms spontaneously.
Single‑trial learning: One exposure suffices to test real‑time episodic encoding.
WWWWhich elements: Must test what (item), where (location) and which occasion (context A vs B).
Hippocampal dependency: Impairment by medial temporal lesions confirms reliance on classic episodic‑memory circuitry.
Describe the three‐phase What–Where–Which (WWWWhich) episodic‑like memory task in rats.
Encode “Which” & “What–Where”: In ContextA (grey walls), rats explore two novel objects (e.g. cube & cylinder) at fixed locations.
Encode alternative “Which”: In ContextB (grid walls), same objects appear but swapped locations.
Test “Which” recall: After a delay, rats return to ContextA and encounter two identical copies of one object (e.g. two cubes). Preferential exploration of the copy in the location never occupied by that object in ContextA indicates recall of the object–place–context pairing.
How long does WWWWhich memory persist in rats and how is it measured?
Persistence: Rats show significant novel‐location exploration (exploration score >0) up to 60min after encoding; performance falls to chance by 120min.
Measure: Exploration preference = (time on novel object–location) − (time on familiar), plotted against log‑delay. A positive score indicates intact episodic‑like memory.
What is the effect of hippocampal (fornix) lesions on WWWWhich versus simple object–location (What–Where) memory?
WWWWhich memory: Fornix lesions abolish the exploration preference at both 2min and 5min delays (performance at chance), confirming hippocampal dependency.
Object–location control: The same lesions do not impair standard What–Where memory (novel‐location preference for a novel object shape), indicating that contextual “Which” recall uniquely requires hippocampal circuits. (Requires EC)
Which brain regions support the “What,” “Where” and “Which” components of WWWWhich memory in rats, and where are they bound together?
- Perirhinal cortex: encodes What (object identity)
- Hippocampus: encodes Where (object location)
- Postrhinal cortex: encodes Which (context/occasion)
Integration: The hippocampus binds object–place–context into a unified What–Where–Which representation; fornix lesions abolish this combined memory while sparing individual components.
If you want to use a What–Where–Which memory test as an early Alzheimer’s biomarker in mice, what three hallmarks must the deficit exhibit?
Early onset: Deficit emerges at the same prodromal stage as in humans - before overt amyloid/tau pathology.
Progressive worsening: Memory impairment intensifies as Alzheimer‑like pathology advances.
Age-related decline in controls: Wild‑type mice show a parallel, milder decline in WWWWhich performance with normal ageing.
Outline the prevalence and clinical stages of Alzheimer’s disease in the UK.
Prevalence: ~500000 affected, ≈60% of UK dementia cases.
Stages:
* Mild cognitive impairment (MCI): prodromal AD
- Early AD
- Mid‑stage AD
- Late/end‑stage AD
What are the earliest cognitive symptoms of Alzheimer’s disease and which memory system remains relatively preserved?
Earliest symptoms: Impaired episodic memory acquisition (difficulty forming new episodic memories) and spatial/navigation deficits.
Spared system early on: Familiarity‑based or perceptual memory can remain intact.
Which higher‑order cognitive deficits tend to emerge later in Alzheimer’s disease progression?
Deficits in executive functions - such as planning, cognitive flexibility and inhibitory control - typically appear in mid to late stages of AD.
Which three human familial‑AD transgenes does the 3xTgAD mouse co‑express, and why is each included?
APPSWE (Swedish mutation): drives overproduction of amyloid‑β.
PS1M146V (Presenilin‑1): enhances γ‑secretase processing of APP, increasing Aβ42.
TauP301L: induces tau hyperphosphorylation and neurofibrillary tangles (frontotemporal‑dementia mutation), without which tangles do not form.
Describe the timeline of neuropathology in 3xTgAD mice.
4months: Onset of spatial memory and synaptic‑plasticity impairments.
10–12months: Appearance of extracellular amyloid‑β plaques in hippocampus and cortex.
~15months: Development of intracellular phosphorylated‑tau neurofibrillary tangles.
Why is the 3xTgAD mouse considered valuable for studying episodic‑like memory deficits in Alzheimer’s disease?
Because it reproduces the key stages of human AD - early synaptic/spatial deficits, followed by progressive Aβ plaque and tau tangle pathology - providing a temporal window to test whether episodic‑like (What–Where–Which) memory declines in parallel with disease markers.
How is “exploration” operationally defined and scored in these spontaneous‑recognition tasks?
A fixed circular/elliptical “virtual zone” is drawn around each object. Exploration time is counted whenever the mouse’s nose/head enters that zone (angle irrelevant).
Zone size is held constant across NOR, OLT, What–Which, WWWWhich and W–W–When tasks.
What is the formula for the displacement score D and what do its values mean?
D= (T novel − T familiar)/Total Exploration
- D>0 → novelty preference
- D<0 → familiarity preference
- D=0 → no preference (“chance”)
Match each spontaneous‑recognition component to its critical brain region:
What (object identity)
Where (spatial location)
Which (contextual/occasion)
What–Where–Which (full episodic‑like binding)
What → Perirhinal cortex
Where → Hippocampus
Which → Postrhinal cortex
What–Where–Which → Hippocampus (integrates all three)
Why is the WWWWhich deficit in 3×TgAD mice a promising early Alzheimer’s biomarker?
It appears by 6mo - before overt Aβ plaques and tau tangles - mirroring prodromal episodic‑memory loss (MCI) in humans, while single‑component familiarity (recency) remains intact.
What are the one‑, two‑ and three‑component spontaneous‑recognition tasks in mice, and which memory each probes?
METHODS:
One‑component:
* Novel Object Recognition (NOR): tests What (object identity).
* Object Location Task (OLT): tests Where (spatial location).
Two‑component:
* What–Where: same object moved to a new place—tests binding of What+Where.
* What–Which: same object presented in a novel context - tests binding of What+Which (context).
Three‑component (WWWWhich):
* Combines object, place and context in a single trial- tests What+Where+Which binding.
RESULTS:
- NOR → perirhinal cortex
- OLT → hippocampus
- What–Where → hippocampus
- What–Which → postrhinal cortex
- WWWWhich → hippocampal integration of all three
In 11‑month‑old 3×TgAD vs. wild‑type mice, how do they perform on NOR and OLT?
METHODS:
* NOR: 3min exposure to two identical objects → 2min delay → 3min test with one novel object.
* OLT: same timing; one object displaced in test.
RESULTS:
* NOR: both genotypes D≈0.18 (novelty preference), no difference → intact object identity memory.
* OLT: controls D≈0.24 (p<0.05); 3×TgAD D≈0.12 (p≈0.05), significantly lower than controls → spatial memory present but impaired.
Describe the What–Which task at 12months and 3×TgAD performance.
METHODS:
* 3min in ContextA with ObjectA.
* 3min in ContextB with the same ObjectA.
* 2min delay.
* 3min test in ContextB with two copies of ObjectA—one congruent, one novel context pairing.
RESULTS:
* Both 3×TgAD and controls show D≈0.25 (p<0.01), with no genotype difference → intact object–context binding.
How does WWWWhich performance in 3×TgAD mice change at 3, 6 and 12months?
METHODS:
* Rats sample two objects in Context1 and two in Context2 (3min each).
* Delays of 2,5,10,15,30min (3min tests).
* D‑scores averaged over 2–15min delays per age.
RESULTS:
* 3mo: both genotypes D>0 (p<0.001) → intact episodic‐like memory
* 6mo: controls D≈0.17 (p<0.001), 3×TgAD D≈0 (ns) → deficit emerges
* 12mo: controls D≈0.08 (p<0.05), 3×TgAD D<0 (ns) → persistent impairment
What is the What–Where–When (recency) task at 14months, and how do 3×TgAD mice perform?
METHODS:
* 5min Acq1 with ObjectA + Object★ (“old”).
* 5min Acq2 with ObjectB + Object□ (“recent”).
* 2min delay.
* 5min test with all four objects arranged so only ObjectA is both old & displaced.
RESULTS:
* Both genotypes preferentially explore the Displaced‑Old object (D>0, p<0.01) → intact recency/place binding even at 14mo.
What pathological milestones do 3×TgAD mice reach and at what ages?
METHODS:
* Transgenic for APPSWE, PS1M146V, TauP301L.
* Longitudinal histology and behaviour.
RESULTS:
* 4mo: synaptic‐plasticity & spatial deficits appear.
* 10–12mo: extracellular amyloid‑β plaques in hippocampus & cortex.
* ~15mo: intracellular phosphorylated‑tau tangles.
* Aligns with gradual emergence of episodic‐like memory deficits in these mice.
What are the three leading models of how the hippocampus contributes to systems‐level memory consolidation?
Standard Consolidation Theory (SCT) – hippocampus is essential for recent episodic memories but not for remote memories once they’ve been fully transferred to neocortex.
Multiple‑Trace/Trace‑Transformation Theory (MTT) – hippocampus is always required to retrieve detailed episodic memories, creating new traces with each retrieval; over time, semanticized (“gist”) versions can reside in neocortex, but vivid recall remains hippocampal‑dependent.
Scene‑Construction (Reconstruction) Theory – neocortex stores the elements of an event permanently, but the hippocampus is needed at recall to reconstruct a coherent episodic scene from those distributed cortical traces.
What is Standard Consolidation Theory?
Standard Consolidation Theory (SCT) – hippocampus is essential for recent episodic memories but not for remote memories once they’ve been fully transferred to neocortex.
What is Multiple Trace/Trace Transformation Theory?
Multiple‑Trace/Trace‑Transformation Theory (MTT) – hippocampus is always required to retrieve detailed episodic memories, creating new traces with each retrieval; over time, semanticized (“gist”) versions can reside in neocortex, but vivid recall remains hippocampal‑dependent.
What is Scene-Construction Theory?
Scene‑Construction (Reconstruction) Theory – neocortex stores the elements of an event permanently, but the hippocampus is needed at recall to reconstruct a coherent episodic scene from those distributed cortical traces.
What are the generally agreed upon ideas about the hippocampus’s role in memory?
- Hippocampus is required for episodic memory acquisition (conversion of STM to LTM)
- Hippocampus is NOT required for STM recall.
- Hippocampus is NOT required for storage or recall of semantic information.
What is the first central issue in the debate over hippocampal involvement in remote episodic recall?
Over time, episodic memories can be transformed into semantic memories.
After this “conversion,” recall of those memories may become independent of the hippocampus.
This predicts that hippocampal lesions should spare “basic” recall of very old memories.
What is the second central issue about the quality of remote episodic recall after hippocampal damage?
MTL amnesics often show intact “basic” remote recall, suggesting no overt deficit.
However, detailed (“rich”) recall - including perceptual detail, viewpoint specificity, vividness, judgments of recollection, and relational associations- may still require the hippocampus.
Thus, hippocampal damage may selectively impair the quality rather than the existence of old episodic memories.
Why might MTL‐amnesic patients appear to have intact remote memory and how does testing method matter?
If you test only for basic recognition (e.g. “Do you remember this event?”), amnesics perform well.
To reveal their deficit, you must probe the richness of recall (e.g. “Describe what you saw,” “How vivid was it?”).
Therefore, success or failure in remote‐memory tasks depends crucially on how (and how deeply) you test memory.
