Learning and Memory Flashcards
1
Q
BRAIN CHANGES
A
- some brain changes (BD/brain stimulation) can effect human beh/perception/cog/emotions/memory
- other changes occur in brain/NS during prenatal development in early life
- changes continue in later life w/ongoing experience/when aging/in dif contexts/environments as during early years
2
Q
EXPERIENCE-DEPENDENT PLASTICITY
A
- changes caused by previous experience can be observed at level of:
BEHAVIOUR - actions/emotions/knowledge
NEURONS - neural network activity
SYNAPSES - interactions between individual neurons
3
Q
HM
A
- BD often causes memory loss for earlier events (retrograde amnesia) within limited time period of hours/days/years
HM (1926-2008) - severe epilepsy; underwent bilateral medial temporal lobotomy; anterograde amnesia (LTM loss for new events/newly learned info) after surgery
- most of HM’s hippocampus/amygdala/subcortical regions/entorhinal cortex = damaged; some probs spared
- parahippocampal cortex fully removed
4
Q
DIF BRAIN AREAS INVOLVED IN MEMORY FORMATION
A
- HM’s cog abilities/STM/episodic memories/info learned pre-operation = largely preserved
- could acquire new motoric skills (ie. tracing shape in mirror) BUT couldn’t recall performing same task before
SCOVILLE & MILNER (1957) - provided first evidence for involvement of hippocampus in memory formation (confirming Bekhterev’s observations)
5
Q
THE MEMORY ENGRAM
A
LASHLEY (1929/1950)
- maze-learning exps w/rats w/parts of cerebral cortex surgically removed
- unsuccessful in attempts to find memory engram (localised memory trace in cortex)
- concluded that learning & memory not located in single area of rat cortex BUT distributed widely across brain
6
Q
NEUROPSYCHOLOGY/PSYCHIATRY RESEARCH LIMITS
A
- major limits for investigating causal relations between neural substrates/beh/psych processes in humans
- ethical consideration of brain manipulations/measurements
- number of patients w/lesions = small
- cases don’t generalise
- coarse damage across functional units
- possible compensatory processes (beh change/functional reorganisation of brain circuits)
7
Q
NEUROPSYCHOLOGY/PSYCHIATRY RESEARCH POSITIVES
A
- (specifically animal models)
- overcome some ethical limits
- replication/precision of lesions
- availability/sample sizes (2-3 pps in primates; more in rodents/non-mammalian models (ie. sea hare Aplysia/Drosophila flies/zebrafish larvae)
- systematic study of wider method/beh/psych processes range providing circuit/synaptic level insights
8
Q
SURGICAL LESIONS VARY IN PRECISION
A
- rhinal cortex includes entorhinal/perirhinal cortex in medial temporal lobe
- traditional method in experimental neuroscience to causally infer bran area function
- neurons ablated applying physical (ie. suction)/pharmacological (ie. neurotoxin injections/pathologically high neurotransmitter concentrations) methods
- neuron loss = permanent/significant damage of non-target tissues in surrounding areas
9
Q
OPTOGENETICS: PRECISE TEMPORARY INACTIVATION OF NEURONS
A
- ChR2 = channel-rhodopsin
- NpHR = halo-rhodopsin
- functional control of targeted cell types using light of specific wavelength
- micro-stimulations during beh tests w/high spatial/temporal precision
- reversible/temporary manipulations allowing in-pp comparisons
- light-sensitive molecules inserted in membrane via genetic tools; animals selectively bred to generate transgenic lines to investigate specific brain circuits
- genetically tractable models (ie. mice/Drosophila flies/zebrafish larvae)
10
Q
EPISODIC-LIKE MEMORIES IN NON-HUMAN ANIMALS
A
- episodic memory = recall of unique experiences explicitly located in past (“mental time travel”) as conscious experience; language based reports
- delayed non-matching to sample task (DNMST)
- test requirements = specific events/objects; familiarity/novelty; context/environment; time
- ability to form/recall memories for personally experienced past events tied to specific context
- novelty/familiarity judgements (delayed non-matching to sample)
CLAYTON & DICKINSON (1998) - retrieval of when/where/what memories
- learning of context-dependent tasks in scrub jays
11
Q
TARGETED LESIONS IN MEDIAL TEMPORAL LOBE
A
SQUIRE & ZOLA-MORGAN (1991)
- hippocampus involved in encoding specific items in context during LTM formation
- perirhinal cortex important for familiarity sense
- parahippocampus encodes context representations
12
Q
DECLARATIVE LTM MEMORY
A
CLARK (2019)
FAMILIARITY/KNOWING WHAT
- declarative (episodic (events)/semantic (facts)) -> medial temporal lobe
- hippocampus (HM)
- mamillary bodies (NA/Korsakoff syndrome)
- neocortex (KC)
13
Q
NON-DECLARATIVE LTM MEMORY
A
CLARK (2019) KNOWING HOW 1. PRIMING - neocortex - exposure to stimulus improves responses to same/similar stimulus 2. NON-ASSOCIATIVE - reflex pathways - brainstem; medial cerebellum parts - startle response 3. PROCEDURAL - striatum - basal ganglia - acquisition of motor skills/habits 4. CLASSICAL CONDITIONING (EMOTIONAL/SOMATIC) - E = amygdala (fear conditioning) - S = cerebellum (eye-blink conditioning/sensorimotor tasks)
14
Q
NON-ASSOCIATIVE LEARNING: HABITUATION
A
- response weakens w/repeated stimulus presentation due to repetition BUT not due to senses/fatigue adaptation
- NOT extinction of associations acquired via learning
15
Q
NON-ASSOCIATIVE LEARNING: DISHABITUATION
A
- repeated tactile stimulation of siphon leads to reduced gill withdrawal response
- response reinstated after stimulation via dis stimulus
16
Q
LTM X NON-ASSOCIATIVE LEARNING
A
CAREW (2000)
- training sessions over 4 days (T1-T4)
- memory recall test on next day (R1)
- test week later (R2)
- memory retained for 3 weeks (R3)
17
Q
PAVLOV’S DOG
A
PAVLOV (1849-1936)
- when dog receives food, it salivates (UR (unconditioned response)); dogs already salivating before given food
18
Q
PD: CS-US CONTINGENCY
A
- if sound (CS) always shortly precedes food (US) then dog will learn that sound predicts food SO starts to salivate (CR) on hearing sound
- contingency = CS predicts occurrence of US meaning; its contingent on prior occurrence of CS
19
Q
PD: APPETITIVE ASSOCIATION
A
- degree of CS/US coincidence determines learning outcome
- temporal contiguity = reinforcement most effective if reward coincides/follows CS shortly after (forward CS/US pairing)
- US should be unexpected/surprising prior to conditioning; animal needs to attend CS
20
Q
EYE-BLINK CONDITIONING
A
- prior to training:
- US = air puff; UR = eye blink
- CS = tone; CR = tone alone elicits eye blink
- neuronal circuit involves cranial nerves/nuclei connecting interneurons/cerebellum
- sensory input US: trigeminal nerve (cranial nerve V)
- CS input = auditory nuclei
- motor output = cranial nerves VI/VII (fascial/eye muscles)
21
Q
CONTEXTUAL/CUED FEAR CONDITIONING
A
- mild foot shock elicits freezing/increased blood pressure/heart beat
- cued conditioning (tone predicts punishment)
- contextual conditioning (box alone predicts punishment)
22
Q
STIMULUS-RESPONSE LEARNING
A
THORNDIKE (1898)
- proposed animals learn based on outcomes of actions (Law of Effect)
- when response followed by reinforcer, stimulus-response (S-R) connection strengthened
23
Q
OPERANT CONDITIONING
A
WATSON/SKINNER
- strongly influence ideas -> 1920s behaviourism emergence as research field dedicated to operant conditioning study
- reinforcement learning = if beh reinforced, it’ll be repeated/extinguished
- animals mainly tested in boxes (Skinner’s box)
24
Q
TEMPORAL MEMORY FORMATION STAGES
A
- shortest memories in sensory buffers (iconic memories) ie. during reading when eye makes saccade
- STM/WM = few seconds to maximally few min long
- intermediate memory = longer but not like LTM
25
Q
ENCODING/RETRIEVAL/CONSOLIDATION
A
- brain activation patterns differ when info encoded/acquired and later recalled (ie. recognition of visual stimulus)
26
Q
CONNECTIVITY CHANGE DURING ENCODING/CONSOLIDATION
A
ENCODING
- hippocampus-dependent encoding of interconnected sensory attributes (stimulus/context)
RETRIEVAL OF MEMORY BEFORE CONSOLIDATION
- hippocampus-dependent retrieval of learned info
RETRIEVAL OF CONSOLIDATED MEMORY
- retrieval w/o hippocampus involvement
27
Q
STANDARD LTM CONSOLIDATION MODEL
A
- connections between hippocampus/various cortical modules critical for encoding/consolidation BUT not later retrieval/reconsolidation
- hippocampus inhibited by prefrontal cortex; time-limited role
- strengthened cortico-cortical connections integrate new memories w/pre-existing ones
28
Q
BEHAVIOURAL MODELS OF SYSTEM CONSOLIDATION IN RODENTS
A
- contextual fear conditioning (classical conditioning of freezing response); single trial training can generate life-lasting memory in same context
- food preference learning (social conditioning of food preference)
- hippocampus lesion causes temporally graded retrograde amnesia
29
Q
RECONSOLIDATION OF MEMORIES
A
SANDRINI et al (2018)
- in unstable state memories can be degraded/strengthened but also modified (ie. false memories)
- beh modifiers = interference/extinction
- pharmacology (ie. protein-synthesis blockers)
- NIBS = non-invasive brain stimulation techniques (ie. rTMS)
30
Q
ENCODING PROCESS
A
ENCODING -> new encoded memories (unstable) CONSOLIDATION -> stored memories (stable) REACTIVATION (RETRIEVAL/REMINDER) -> stored memories (unstable) RECONSOLIDATION -> altered memories (degraded/strengthened/updated) (stable) MODIFICATION - beh/stressor events - pharmacological agents/NIBS
31
Q
SUMMARY
A
- memory distributed across cortical/subcortical brain areas (ie. hippocampus/mammillary bodies/thalamus/cerebellum)
- damage to brain areas causes amnesia
- memories divided into declarative/non-declarative
- animal research uncovers mechanisms at level of brain/neural networks/synapses
- what/when/how memory depends on learning process (ie. associative/non-associative learning)/stimuli; sometimes rewards/punishments
- memories differ in duration (sensory buffer/STM/ITM/LTM)
- consolidation/reconsolidation of LTM
32
Q
HEBB SYNAPSE
A
RAMON Y CAJAL (1893)
- first proposed that site of contact between neurons could play role in memory formation
FOSTER & SHERRINGTON (1897)
- named them synapses
HEBB (1949)
- theory that some connections in neural networks could be strengthened if frequently activated/weakened if used less
- Hebb synapse concept implies strength of synaptic transmission can ^ if presynaptic cell repeatedly/persistently activates postsynaptic cell
33
Q
SYNAPTIC PLASTICITY IN LEARNING/MEMORY
A
- synaptic plasticity = biological processes at synapse by which synaptic activity patterns change (increase/decrease synaptic strength)
- when axon of cell A is near enough to excite cell B to repeatedly/persistently take part in firing it, some growth process/metabolic change takes place in one/both cells so that A’s efficiency (as a cell firing B) increases
34
Q
SEARCH FOR MEMORY ENGRAM +
A
- fundamental principles of cellular/molecular mechanisms underlying learning/memory uncovered in Alysia
- signals transmitted as few individually identified sensorimotor synapses control gill withdrawal response
KANDEL et al - dissected whole neural network that steers motor-neurons of gill muscles
- small number of neurons w/large-sized soma/axons
- possible to measure/manipulate neural signals in single sensory/motor neurons (pre/postsynaptic sensorimotor synapse cells) during acquisition/memory formation/recall
35
Q
SYNAPTIC PLASTICITY IN LEARNING/MEMORY
A
- changes in presynaptic neuron can include:
1. short-term plasticity (enhancement/reduction)
2. gain control (change in neurotransmitter amount released for given signal)
3. temporal filtering (change in selectivity for frequency range of spikes arriving in axon terminal) - synaptic transmission enhancement (ie. presynaptic facilitation (Aplysia’s gill synapse))
- short term facilitation (v brief/milliseconds)/potentiation (few seconds -> minutes)
- short-term depression (opposite effect; decreases PSP)
36
Q
PRESYNAPTIC DEPRESSION
A
- reduction of neurotransmitter release in STM
SHORT-TERM HABITUATION
37
Q
PD: SHORT-TERM HABITUATION
A
- when siphon first stimulated by water squirt; Aplysia retracts gills to protect it; reflex mediated by sensory neurons synapsing directly upon motor neurons that withdraw gill
- if squirted repeatedly, animal habituates to stimulus; no longer retracts gill; short-term habituation results as sensory neurons release less transmitter
38
Q
PD: LONG-TERM HABITUATION
A
- if siphon squirted repeatedly over days, animal habituates faster each day; eventually shows almost no response
- long-term habituation due to retraction of some synaptic terminals
39
Q
MODULATORY INTER-NEURONS
A
- can influence how much/for how long neurotransmitter is released
- presynaptic facilitation eg = changes involving inter-neuron modulation; modulation causes an increase in neurotransmitter release
40
Q
POSTSYNAPTIC NEURON CHANGES
A
- evidence provided by studies investigating mechanisms of associative (classical/operant conditioning)/spatial learning
- presynaptic neuron -> postsynaptic neuron changes -> both neurons
41
Q
SPATIAL LEARNING IN RODENTS
A
MORRIS (2008)
- escape learning task in water maze by finding hidden platform in fixed location
- dif training/testing protocols to investigate learning/memory/navigation mechanisms
- lister-hooded rats have much better vision than white rats (common in research)
42
Q
HIPPOCAMPUS LESIONS PRIOR TRAINING
A
MORRIS et al (1982)
- don’t specifically impair working/reference memory BUT spatial memory; lesions after training have less strong effect on it
PHASE 1
- hidden platform
PHASE 2
- platform hidden but marked w/beacon (cue-based navigation); all rats show same escape latency
PHASE 3
- reversal to hidden platform; rats w/hippocampal lesions performed poorly again
43
Q
HIPPOCAMPAL FORMATION ENCODES SPACE LOCATIONS
A
MOSER et al (2015)
- black lines show trajectory of foraging rat in 1.5m diameter wide square enclosure
- each red dot depicts 1 spike fired via cell (microelectrode recordings in freely moving rats)
- cyan triangles illustrate spatial regularity (hexagonal grid) of firing pattern characteristic for grid cells
- colour-coded spiking rate map (blue = lowest activity; red = highest)
44
Q
HIPPOCAMPUS INVOLVED IN SPATIAL MEMORY FORMATION
A
- neurotransmitter = glutamate
- can take slices from hippocampus that preserve functioning network; can be kept alive; recordings performed ex vivo
- 3 main pathways:
PERFORMANT - entorhinal cortex input
MOSSY FIBRE - dentate gyrus to CA3 pyramidal cells
SCHAFFER COLLATERAL - CA3-CA1 pyramidal cells
45
Q
LTP = POSTSYNAPTIC MECHANISM
A
- LTP = long term potentiation; can last hours
- LTD = long term depression
ANDERSSON (1966) - found in perforant pathway of hippocampus of anesthesised rabbits that during repetitive stimulation additional strong depolarisation w/many fast pulses during few seconds (tetanus) caused increase in neuronal firing of postsynaptic cell
BLISS & LOMO (1973) - continued work; discovered LTP demonstrating frequency potentiations can be long-lasting
- LTP found in other hippocampus paths too
46
Q
AMPA RECPTORS IN CA1 PYRAMIDAL NEURONS
A
- AMPA receptors = ionotropic receptors (ligand-gated ion channels)
- AMPA receptors open if glutamate binds to them; when open Na+ flow into postsynaptic neuron
- synapse is excitatory as Na+ influx depolarises membrane (EPSPs)
47
Q
CA1 NEURONS
A
- also have NMDA receptors in dendrites
- NMDA receptors both ligand/voltage-gated
- when cell at rest NMDA receptors blocked by Mg2+
- binding of glutamate neurotransmitter necessary BUT alone insufficient to open them
48
Q
NMDA RECEPTORS ACT AS COINCIDENCE DETECTORS
A
- open when both conditions met:
1. binding of glutamate
2. membrane depolarises above threshold expelling Mg2+ plug - leads to influx of Ca2+ ions into postsynaptic cell; also contributes to EPSP
49
Q
MORE RECEPTORS FOR STRONGER EPSPs
A
- in dendritic spin vesicles contain AMPA receptors in membrane
- if NMDA receptor opens it lets in Ca2+ from synaptic cleft; Ca2+ activates proteins that make those vesicles bind w/cell membrane in synaptic cleft
- then ^ AMPA receptors in active zone; ^ Na+ will enter each time neurotransmitter released
- ^ AMPA receptors in cell membrane lasts many hours
50
Q
STRONGEST LTM EFFECT
A
- growth of new dendritic spines w/synapses
- high Ca2+ influx activates intracellular enzymes (protein kinases)
- PKA/PKC/CaMKII (calcium-calmodulin dependent protein kinase II) activate transcription factor CREB (cAMP response element binding protein)
- CREB targets many genes that required for growing new dendritic spines/synapses
51
Q
INVESTIGATING ROLE OF NMDA RECEPTORS
A
MORRIS et al (1986)
- AP5 (APV too); selective NMDA receptor antagonist
- AP5 treatment of hippocampus cells suppresses LTP
TSIEN et al (1996)
- NMDA receptor knockout mice = using genetic tools to study brain functions
- LTP absent in NMDA knockouts; normal in wild-type animals/controls (also knockouts BUT w/intact NMDA receptors)
52
Q
MEMORY CONSOLIDATION REQUIRES PROTEIN SYNTHESIS
A
- pharmacological agents used to dissociate dif stages of encoding/reconsolidation
- drug manipulations relatively brief/accurately timed/usually reversible (in-pp control before/after treatment possible)
- targeted intracranial drug delivery circumvents BBB (blood-brain barrier)
- protein-synthesis blocker applied in LTM studies involving hippocampus/amygdala/prefrontal & insular cortex; anisomycin/rapamycin = amnesiac agents affecting consolidation/reconsolidation
53
Q
ROLE FOR ADULT NEUROGENESIS IN SPATIAL LTM
A
NOTTEBOHM (1985)
- precise role of new brain cells born in adulthood unknown; presumable repair/plasticity
- hippocampal neurogenesis (ie. DG (dental gyrus) found in many mammals)
54
Q
STRUCTURAL CHANGES IN HIPPOCAMPUS
A
- associated w/extensive spatial learning/route following
MAGUIRE et al (2000) - response to environmental stimulation under natural conditions
- London taxi drivers have larger hippocampi
- compared to bus drivers have greater grey matter volume in mid-posterior hippocampi; less volume in anterior hippocampi
55
Q
ENVIRONMENTAL ENRICHMENT ENHANCES BRAIN
A
STUART et al (2017)
- enhanced opportunities for learning perceptual/motor skills/social learning
- besides learning complex info ^ processing needs; changes in physio/activity rhythms
- can influence experimental outcomes
- evidence how function changes in specific brain areas ie. measuring synaptic density changes; correlate w/beh performance and other indicators for cog/physical health at dif ages
56
Q
VISUAL DEPRIVATION CAUSES STRUCTURAL CHANGES IN BRAIN
A
LE VAY, WIESEL, HUBEL (1980)
- kitten/monkey exps reveal development/utilisation of V1 structures (orientation/ocular dominance columns) depend heavily on sensory experience during/after early crit period
- brain functions compete for space; reorganisation takes time
- alternating ocular dominance columns in layer IV of primary visual cortex (V1) receives input from either right (bright stripes after injection of radioactive dye)/left (dark stripes) eye
57
Q
RECRUITING NEW BRAIN AREAS WHEN A SENSORY SYSTEM DOESN’T DEVELOP
A
MERABET & PASCUAL-LEONE (2010)
- cross-modal recruitment of occipital visual cortex in blind/auditory cortex in deaf reported
1. occipital recruitment for tactile processing (ie. Braille reading/sound/localisation/verbal memory)
2. recruitment of auditory/language-related areas for viewing sign language/peripheral visual processing/vibro-tactile stimulation
58
Q
AGE-RELATED MEMORY CHANGES
A
SPRENG et al (2010)
- w/aging humans experience memory type decreases including spatial memory/navigational skills due to neuron/connection loss
- memory impairment = neurodegenerative disease symptom
- evidence for cholinergic inputs decrease to hippocampus/cortex
- white matter can change in older subjects to allow task-dependent learning in specific regions dif to younger pps
59
Q
TEMPORAL PLASTICITY CONSTRAINTS
A
- neural plasticity takes many forms
- time courses differ over life span
- important to find mechanism enabling/inhibiting it
60
Q
SUMMARY II: MEMORY FORMATION X PLASTICITY
A
- Hebb proposed new approaches to understand beh via brain function perspective
- Hebb synapse illustrates why/how signal transmission changes at synapse
61
Q
SUMMARY II: SYNAPTIC EFFICIENCY CHANGES OVER TIME
A
- presynaptic facilitation/depression = changes underlying STM
- LTP/LTD = stable/enduring change
- plasticity in neurons at molecular level
- structural changes in connectivity/synaptic density
- pharmacological agents/genetic tools to dissect mechanisms of learning/memory
62
Q
SUMMARY II: SPATIAL LEARNING INVOLVES HIPPOCAMPUS
A
- LTP can occur at several hippocampal formation sites
- AMPA/NMDA receptors both present in postsynaptic membrane
- NMDA receptor = coincidence detector; required for LTP
63
Q
SUMMARY II: PLASTICITY = DEFINING BRAIN FEATURE
A
- prominent in neural development BUT also extends over life span
- neurogenesis contributes to brain plasticity/repairs; may aid learning
- some plasticity form limited to early critical/sensitive period
- contributes to causes/treatments of psychopathology
- sensory/motor systems show plasticity
