Learning + Memory in Mammals Flashcards
How can memory be classified?
- Temporality
= time course of information storage - Nature of information stored
= learning + memory essential for full effective functioning and survival
= processes are evolutionarily conserved across species
What are the different time courses of memory?
Working memory (on task memory)
Short-term memory (ms to minutes)
Long-term memory (days to years)
What is Working Memory? (+ a way to measure in an animal model)
Working Memory
= task specific, ordered in time and space
= limited capacity system (temporarily holds info available for processing)
= important for reasoning + guiding decision making behaviour
= allows stored info to be updated and manipulated (unlike short-term memory)
= deleted after use
= dynamic, can be disturbed easily
= if info lost , no retrieval
8-arm radial maze test
= classic rodent working memory test
= arms are baited with food
= rodents explore arms but have to be efficient to remember which arms they have already visited
= info is of no value after task completed
= memory reset for next task
What is short term memory?
= storage of info, but info is not manipulated
= limited capacity (~ 7 items)
= often data rich , not suitable to store all of it in the long-term
= selectivity transferred over to long-term memory (hopefully on the necessary info)
What is Long-term memory (+it’s classifications)?
= ? unlimited capacity
Explicit / Declarative memory
= conscious
= episodic (events) and semantic (facts)
= flexible - lots of info associated under different circumstances
Implicit / Nondeclarative
= unconscious memory / automatic
= inflexible - tightly connected to circumstances when learned
= split into non-associative and associative
Non-associative
= learning about one type of stimulus
= timing not important
= habituation - desensitisation
(repeated exposure of stimulus that is not relevant e.g. fireworks = must suppress irrelevant or misleading info)
Associative
= learning about relationship between 2 stimuli / between stimulus and response
Classical Conditioning
= e.g. Pavlovian Conditioning
= learn importance of a predictor stimulus
= e.g. US - puff of air to eye, CS - 100-Hz tone , response of both = blink
Operant Conditioning
= trial and error learning
= random activity becomes paired with a reinforcer
e.g. rat behaviour in operant box
= complex behaviour (e.g. pressing lever) paired with positive reinforcers (e.g. food) or negative stimuli (e.g. loud noise)
What are the distinct operations (stages) of explicit learning?
- Endcoding
= attending to relevant info + linking it with an established memory
= influenced by motivation - Storage
= neural mechanisms by which memory is retained over time - Consolidation
= temporary and labile info becomes more stable
= involves gene expression, protein synthesis, structural synaptic changes
= newer concept of consolidation of long-term memory into neural systems (systems consolidation) - Retrieval
= retrieve the stored info - ?Potential re-consolidation?
= recalled info is labile and can be altered slightly
= false-memories
What is the best case study in learning + memory?
= Patient H.M
= showed that memory is a distinct cerebral function
(separate from other cognitive / perceptual functions)
= showed that the Medial Temporal Lobe plays a v. important part in memory formation
(i.e. hippocampus, amygdala, adjacent parahippocampal cortex)
= he had uncontrolled temporal lobe epilepsy = had a bilateral lesion of the temporal lobes
(inc. hippocampus, amygdala and associated cortex)
Intact
= same IQ
= working memory
= semantic memory
= no retrograde amnesia (memories of events prior to surgery intact)
= motor skills
BUT had anterograde amnesia
= memory only lasts couple of minutes
= new short-term memories not converted into long-term memories
What brain areas are involved in the different types of learning?
Overall called the Neocortex
= storage place for long-term memory
= specialised
(e.g. cortical areas involved in visual processing)
= made up of the following:
Prefrontal cortex
= executive function
= working memory
= influences memory retrieval (from other neural systems)
Parietal lobe
= navigation
Cerebellum
= motor memory
Occipital lobe
= visual processing
Temporal lobe
= Hippocampus = memory encoding, consolidation and retrieval
(also very important in rodent spatial learning)
= Amygdala = emotional memory
How to test rodent spatial learning? (without olfactory cues)
= The Morris Water Maze
= animals trained to find a submerged platform to escape from the water
= rodent uses external cues in the room for navigation
Acquisition phase
= Latency = time to find platform
= Distance = length of swim path (analysed using video tracker system)
Memory recall test (probe trial)
= platform removed
= can find out where animal is searching
= if memory has formed, animals spend more time in quadrant where platform was previosuly
= rats with hippocampus lesions / with β-amyloid have worse results
What are the memory functions of the hippocampus?
Rodents
= lesions of hippocampus impairs:
= complex association learning
= spatial learning and memory
= memory consolidation (from short- to long-term memory
Humans
= lesions of hippocampus impair:
= transfer of short-term memory to long-term memory
(? issue with encoding / consolidation)
= Hippocampus plays role in converting short term memories to long term memories
(by processing new memories and temporarily storing them in cortex - prior to permanent storage)
What is synaptic plasticity?
Info is processed in distributed neuronal networks
= info is specific (e.g. visual, tactile, gustatory)
= info processed in different brain areas
Modulation of synaptic activity in these neuronal networks
= can keep info for the short or long term
What does working memory depend on?
= persistent neural activity in the prefrontal cortex
= evidence from in vivo recordings of neuronal activity in PFC of non-human primate
= they used DMTS (delayed match-to-sample) working memory task
(image shown , taken away, second image shown, press lever if image recognised for reward)
= showed neurons in PFC persistently fire in the delay period (through 2 mechanisms)
- changes in PFC neuronal membrane properties
(e.g. Ca2+ activated non-selective cation channels insertion into membrane( - changes in communication between local neurons that promote recurrent firing
How does long-term memory form?
= does NOT depend on persistent neuronal firing (like working memory)
= involves long-lasting changes in strength of synaptic connections
= (synaptic plasticity)
= effects characterised well in hippocampus through electrophysiology, drug challenged and genetic mouse models
(LTP = long term potentiation = mechanism by which long-lasting, activity-dependent changes in synaptic strength are generated by high frequency stimulation of presynaptic neuron = could underlie long term memory)
What method is used to measure LTP?
= hippocampal slice electrophysiology
= study Schaffer collateral - CA1 pathway
Presynaptic cell
= stimulate Schaffer collateral neurons with electrical high frequency tetanic stimulatuon
Postsynaptic cell
= record what happens to neurons in the CA1 hippocampal subfield
= measured as field potentials (electrical depolarisations) OR action potentials (neuronal firing) in the CA1 field
= increase in postsynaptic response in response to same level of stimulation
= means that synapses involved have been potentiated
= LTP has occured
(negative deflection represents depolarisation of post-synaptic neurons)
How is LTP induced at excitatory (glutamatergic) synapses?
Many forms of LTP at glutamatergic synapses
= dependent on the NMDA receptor and AMPA receptor
Under basal synaptic conditions
= NMDA receptors blocked by Mg2+ ions and do NOT allow cation (Na+ / Ca2+) influx into neuron
= glutamate acts on AMPA receptors to depolarise post-synaptic cell, allowing Na+/K+ to enter
Induction of LTP
= high presynaptic activity (e.g. from HFS) causes strong depolarisation in post-synaptic dendrite
= releases the Mg2+ block from NMDA receptor
= large Ca2+ influx into dendritic spine
= NMDA are coincidence detectors = MUST have glutamate bound + post-synaptic membrane must be depolarised (Mg2+ block removed)
= intracellular Ca2+ stimulates intracellular signalling cascades (activation of protein kinases + CREB)
= CREB signalling promotes generation of retrograde signalling molecules = act on presynaptic bouton = enhance neurotransmitter release
= CAMKII promotes integration of additional AMPA receptors into dendritic membrane
(pathways conserved in drosophila, aplasia and mammals)
LTP is established
= synapse strengthened as likelihood and quantity of presynaptic neurotransmitter release is increased
AND
= the post-synaptic membrane is more responsive (more AMPA receptors)
How is LTP associative?
Neuron = has specific threshold for induction of LTP
e.g. stimulating one input with HFS
= may have v. high threshold for inducing LTP
= stimulation did NOT induce LTP
BUT when stimulating 2 independent projections to a neuron simultaneously
= LTP is observed at lower frequencies
= this can explain conditioning
(e.g. eye-blink reflex driven by air puff (US))
= strength of synapse for conditioned stimulus changes
= links the two stimuli with the response
= therefore tone (CS) drives response
Compare LTP and LTD.
How is LTD dissociative?
= asynchronous inputs onto a neuron result in LTD
= asynchrony resulting in LTD could keep neural networks separate (not processing associated information)
= less known about the relevance of this behaviour
(may be involved in behavioural flexibility)
= transgenic mice with selectively LTD (but not LTP) fail to learn new location in morris water maze
What is Memory Consolidation? What are the 2 models?
= process by which temporary, labile memory is transformed into more stable, long-lasting memory
New memories
= originally stored in hippocampus and neural networks in neocortex
Model A = Through System Consolidation
= hippocampus guides reorganisation of information in neocortex
= becomes permanently stored and seperate from hippocampus (like in H.M)
Thought to depend on ‘neural replay’ during sleep
= could be basis on dreams - speculative
Model B = May involve the integration of new information into cortical networks that already hold prior knowledge
= update existing ‘schema’
What is the Novel Object Recognition Test (NORT)?
= mice show a preference for exploring novel objects in their environment
= can be used as an indicator of learning and memory
= more exploration time spent with the novel object indicates that mice have a memory of the familiar object
