Learning & Memory 2 Flashcards
What is easier to study?
- Declarative Memory/Learning
- Procedural Memory/Learning
- Procedural Learning
Subjects learn to make a particular response such as a movement in response to a stimulus (these are much more easily studied in animals compared to complex experiences in declarative learning)
What type of learning was Pavlov known for?
- Conditional Learning
(procedural learning)
What types of classic conditioning did Pavlov study?
- Autonomic Reflexes (salivation)
- Skeletal Muscle (leg-flexion) reflexes
These reflexes were conditioned to previously neutral stimuli
What did Skinner develop?
What type of learning was he testing for?
- Developed ‘Skinner’s box’
- This was used to study operant conditioning
(rat with a lever for food reward)
What did Thorndike develop?
What type of learning was he testing for?
- Developed ‘puzzle boxes’
- Tested cats abilities to learn complex escape procedures
(cats in small cages with complicated latches they had to undo)
What did Skinner conclude?
- Animals learn via associative mechanisms to form memory
(on a basic level - humans do not neccesarily chain up two things on a behavioural level as shown in skinner’s box)
Humans can change things in nervous system via non-associative learning
What are the two types of procedural learning?
- Associative Learning
- Non-Associatie Learning
State the two non-associative learning types?
- Habituation
- Sensitisation
What is habitutation?
- Non-Associative Learning
- Gradual waning of a response with repeated presentations of a stimulus
(sitting on a seat for a long-time –> are no longer aware of the sensory information from the bottom of your seat as when first sat down)
What is sensitisation?
- Non-Associative Learning
- Enhancement of responses to a stimulus after exposure to a highly arousing event
(e.g. if half asleep (habitutation to quiet sounds) but hear loud bang you start to hear the slightest sounds)
What is associative learning?
- Associating one stimulus with another stimulus
What are the two associative learning methods?
- Classical Conditioning
- Operant Conditioning (instrumental learning)
What is classical conditioning?
- Associative Learning
- Subject learns the predictive value of one event (often behaviourally neutral) for another (usually behaviourally significant)
(e.g. ringing of bell signalling food - Pavlov) - i.e. one stimulus associated with another
What is operant conditioning (instrumental learning)?
- Associative Learning
- Subject learns that their responses have behaviourally outcomes
(e. g. Thorndike’s cats manipulate a catch to escape or Skinner rat presses a lever to obtain food)
* Appropriate responses are reinforced by the behavioural outcomes
(stimulus becomes associated with a particular response)
What rule did Donald Hebb suggest?
When Axon of Cell A is near enough to excite cell B or repeatedly or persistently take part in firing it, some growth process or metabolic change takes place in one or both cells so that A’s efficiency, as one of the cells firing B is increased.
(neurone A communicated with B causing it to fire –> causes the pathway between them to strengthen –> leading to associative strength change via synaptic changes –> basis for learning & memory)
What is most likely to be the underlying mechanism of learning & memory formation?
- Alterations in synaptic strength
(this definitely takes place and is most likely the main underlying cause of memory & learning however it may not be - may be adjunct - non-synaptic forms of excitability changes)
What does glutamate from a pre-synaptic terminal act on post-synaptically?
- Ionotropic AMPA receptors
- Ionotropic NMDA receptors
- Metabotropic Glutamate Receptors
When are NMDA receptors activated?
- When post-synaptic membrane is sufficiently depolarised to overcome the Mg++ block
In a normal state, what happens at the post-synaptic membrane of a neurone?
- NMDA Receptor –> blocked by Magnesium Ion (Mg++)
- AMPA Receptor –> is acted on normally by glutamate
When is NMDA activated?
What happens?
- Usually blocked by Mg++
- Sufficient depolarisation (due to strong drive from AMPA) –> causes Mg++ block to come out
- Allows for Ca2+ influx through NMDA to occur
- Causing even further depolarisation of the membrane
Brieflly, what is the NMDA receptor?
- Level Setter Device
- Only opens when the membrane is sufficiently depolarised by AMPA
How is long-term potentiation (LTP) induced?
There are two ways
- Strong (tetanic) activation of an afferent input –> which is sufficient to activate NMDA receptors
- Weak input that coincides with post-synaptic depolarisation caused by another strong input
What does LTP stand for?
- Long-Term Potentiation
What is LTP involved in?
- Learning & Memory
What occurs once a neurone/synapse has undergone Long-Term Potentiation?
- Increased number of AMPA receptors in the membrane
- Post-Synaptic Response increases –> giving a much stronger post-synaptic response (stronger EPSP) to afferent signals
- Increased firing likelihood (to afferent signals) - i.e. cells more excitable
Where does LTP take place?
- Many different brain regions
(first demonstrated in hippocampus in CA1)
What two ways related to weak inputs can cause LTP?
- Weak input that coincides with post-synaptic depolarisation caused by another strong input
- Two weaker inputs that summate to depolarise the neuron (each can undergo LTP)
LTP can be associative
What can lead to Long-lasting Potentiation (LTP)?
- Brief high-frequency tetanus
(must be input specific)
What happens in the future after LTP?
- Post-synaptic neuron would respond to the input (even if weak)
Describe briefly the process of associative learning between the smell & sight of a rose using the LTP mechanism.
- Sight or smell of the rose on its own is too weak to b the neurone
- If they occur together –> LTP takes place at both their synapses/inputs
- Neurone can now recognise the smell or sight of a rose (do not need to be together anymore) - modalities are associated (it will fire if either or both appear - cannnot distinguish - becomes the ‘rose cell’)
(this is likely to occur over whole networks of neurones rather than individual ones as described)
What is LTP dependent on?
- Post-synaptic Ca2+ levels
How is Ca2+ involved in LTP?
- Ca2+ enters through NMDA receptors –> activates protein kinases (PKC)
- Phosphorylate AMPA receptors (activate them)
- This changes effectiveness of existing AMPA receptors & contributes to inserting new AMPA receptors
- Post-synaptic Ca2+ levels are critical & depend on the exact level of NMDA receptor activation
What happens if Ca2+ levels are not very high?
- Long-Term Depression (LTD)
What causes LTD (Long Term Depression)?
- Input stimulated with a low-frequency tetanus
- Input-specific LTD can be measured
Describe the process of Long-Term Depression (LTD)?
When does it occur?
- Intermediate Calcium Levels (due to NMDA)
- Reverse Process
- Traffics AMPA out of the membrane
- Reduces efficacy at the synapse
Why is it important that LTD exists?
- If LTP was the only synaptic mechanism available for learning –> then neural networks may saturate through a lifetime
- Everything would rack up & up (need the ability to go up or down depending on representation)
LTP & LTD work togetehr to make the changes needed in memory formation
What does information storage in learning depend on?
Where does this take place?
- Depend upon LTP & LTD processes
- Found widely in the nervous system including hippocampus & neocortical regions (different receptor sub-types in different neurones but basic rule applies to all)
What is important in memory formation in the cerebellum?
Synaptic Plasticity
What are the two types of inputs going to purkinje cells in the cerebellar cortex?
- Climbing Fibre
- Mossy Fibres (synapse with parallel fibres of granule cells)
Where do the inputs into the cerebellum come from?
- Climbing Fibres –> INFERIOR OLVIES
- Mossy Fibres –> PONTINE NUCLEI (+ others)
How does Long-Term Depression (LTD) occur in the cerebellum?
- Conjunctive (both) activation of climbing fibre inputs & parallel fibre inputs
- Leads to long-term depression of parallel fibre synapses upon Purkinje Fibres
What does EPSP stand for?
- Excitatory Post-Synaptic Potentiation (EPSP)
How is LTD stimulus specific?
- Recognises a particular parallel fibre input and pairs it with a climbing fibre input
(causes learnign in purkinje cell)
Describe the molecular mechanism of Long-Term Depression (LTD) in the cerebellum.
- Activated parallel fibres –> causes activation of AMPA Receptors & Metabotropic Glutamate Receptors
- Metabotropic Glutamate Receptors –> activates a signalling pathways through DAG –> activating PKC (protein kinase C - calcium dependent kinase)
- Climbing fibre depolarises at the same time
- High post-synaptic calcium levels are needed –> for PKC –> fulfilled by Voltage Gated Calcium Channels (no NMDAs in purkinje cells)
- Allowing strong depolarisation
- Due to multiple contacts from climbing fibres –> many AMPA receptors are associated with a single purkinje cell –> causing strong calcium influx & PKC activation
- This causes phosphorlation
- AMPA receptor phosphorylation –> causes crippling in transmission via AMPA receptors –> decreasing AMPA receptor efficacy (reverse role)
- This causes long-term depression
Describe the inputs from the climbing cells to the purkinje fibres.
- Multipe contacts from climbing cells to purkinje cells
- Climbing fibre has special input of many AMPA receptors associated with purkinje cell (multiple contacts)
- Opens thousands of AMPA receptors when activated –> causing Na+ influx
- This causes voltage-gated channel opening –> causing Ca2+ influx
Describe conditioned eyelid blinking experiment.
- Movement of third eyelid elicited due to airpuff
- Repeated many times
- Unconditional stimulus evokes an unconditional response
Eventually the blink occurs without an airpuff at all (closure of eyelod os very well timed)
Initially the quiet tone conditonal stimulus (CS) does not evoke a blink however after repeats with unconditional stimulus –> conditional stimulus evokes a conditioned response
What occurs in a large cerebellar lesion?
- Abolished classical (pavlovian) conditioning of the eyeblink
Describe the molecular mechanism briefly of the airpuff & blink and how it leads to conditoined eyelid blink responses.
- Climbing fibres (from inferior olive) –> fire when the airpuff takes place and there was no blink (i.e. mistake)
- Pontine nuclei –> contains pathway bringing tone & light information –> via parallel fibres (initially mossy fibres) –> to the purkinje cell
- These two types of stimuli take place at the same time at the purkinje fibre –> causing associative learning
*
What is an important component of normal eyeblink conditioning and thus cerebellum-dependent procedural learning?
- LTD (Long-Term Depression)
What happens in mice which have inhibition of PKC in purkinje cells?
- Unable to undergo LTD
- Blinks are wrongly timed to the air puff
- Unable to learn associative nature
Mossy-parallel fibre system & climbing fibre system –> need to work together –> to give correct motor response –> to give accurat e& correctly timed associatievly learned blink response (via LTD)
