Learning and memory Flashcards
Declaritive memory
available to the conscious mind and can be encoded in symbols and language
Explicit memory
memory that can be consciously recalled
Implicit memory
memory that cannot be consciously recalled
What are the three types of implicit memory?
procedural memory
classical conditioning
priming
Advantages of using simple systems to study memory (snails, worms insects)
complicated nervous systems but stereotypic and large axons which are easier to record from
temp dependence allows switching on and off of neurons/genes
Habituation
decreased amplitude of response due to repeated stimulus
Sensitisation
increased amplitude of response
What are two examples of simple forms of memory?
habituation
sensitisation
Aplysia gill withdrawal reflex
gill withdrawal reflex caused by touch or water jet
habituation casued by repeated stimulus
sensitisation caused by tail/head pinch or shock, involves presynaptic input from sensory neurons with serotonin and g protein action
Associative learning
very pavlovian like
weak siphon touch paired with strong shock meaning response is much bigger than before and more long term
timing is critical for shock being associated to stimulus
Why does a shock stimulus along with siphon touch give a bigger response?
calcium influx from L29 which is the extra neuron that detects noxious stimuli
happens at the same time as sensory neuron depolarisation so there is much more cyclic AMP and PKA produced
Hebbian synapse
coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthening the synaptic connections between them
What type of memory is the hippocampus particularly involved in?
spatial
Hippocampal pathway
entorhinal cortex > dentate gyrus > CA3 > CA1 > output via fornix and subiculum
Where does long term potentiation usually occur in the memory pathway?
CA3 to CA1 synapses
What is the long term potentiation phenomenom?
high frequency sitmulus causes amplitude of EPSPs to become bigger
How does LTP show cooperativity and sensitivity?
shows input sensitivity as it only acts on the synpases that are activated
shows cooperativity as it allows two pathways converging on the same target to be strengthened if fired together
3 types of glutamate receptor
NMDA
APMA
mGlu
Where could the cooperative characteristics of LTPs come from?
may be a result of NMDA receptors as they have a voltage dependent Mg2+ block which requires indirect pre-activation by a seperate depolarising input
What are the two stages LTP can be split into?
early and late
OR induction and expression
Early stage LTP NMDA activation
increase in Ca2+ conc
activation of calmodulin kinase II which phosphorylates itself into stable active conformation to then phosphorylate other proteins
AMPAfication
increase in the number of AMPA receptors on the postsynaptic terminal
Late stage LTP
lasts much longer and requires protein synthesis so takes much longer
How could cAMP signalling be critical in late stage LTP?
cAMP activates protein kinase A which activates other proteins and phosphorylates proteins inside the nucleus
binds to CRE which then acitvates promoter, leads to expression of genes that change synapse
What are the effects of inhibition of LTP?
inhibits some memory formation so must be somewhat involved but only for some and isn’t sufficient on its own
some memory enhancing drugs increase LTP
Mutations of what pathways affect aspects of learning?
CaMKII
NMDARs
cAMP
Long term depression
related to memory and is the opposite of LTP
decreases the synaptic gain when memories are formed
What parts of the brain are important for LTD?
cerebellum
hippocampus
LTD cerebellar circuitry
inputs are from positive mossy and climbing fibres
output to DCN are negative purkinje fibres
mossy fibres
What is the difference between how mossy and climbing fibres synapse?
mossy fibres only synpase to one purkinje cell but it does this many times through parallel fibres
climbing fibres synapse with many different purkinje fibres and wrap around them
How can you make changes to a synapse by electrical stimulation?
stimulate parallel fibre and climbing fibre at the same time
causes decrease in amplitude of EPSPs
What mechansisms are involed in cerebellar LTD?
does not involve NMDA receptors
metabotropic Glu-R, AMPA R and VGCCs
needs co-incident activation of both signalling pathways
Climbing fibre to purkinje
AMPA
Parallel fibre to purkinje cell
m-Glu and AMPA receptors
Climbing fibre to purkinje cell
AMPA receptors
How is LTD different to LTP?
PKC phosphorylates AMPA GluR2 subunit
reduces currents by endocytosis
Where does hippocampal LTD occur?
CA3-CA1 synapse with LFS
How is hippocampal LTD similar to LTP?
Calcium dependent but this is due to different mechanisms
How does the amount of NMDA receptor activation relate to LTP/LTD?
small amount of activation means that LTD is more likely
large amount of activation means that LTP is more likely
What governs the balance between LTD and LTP?
small increases of Ca2+ from NMDAr trigger phosphatase action and reduce AMPA efficacy
large increses activate from protein kinases which increases AMPA efficacy
Does LTP + LTD = memory?
to some extent, but long term memory is a distributed and structural change
shape of neuron may change- number of spines on dendrites may increase/decrease
Adaptation
originates in the retina and is downstream
decrease in activity/striking rate
often the reason for visual illusions
Olfactory pathway summary
odour → olfactory receptor neurons → projection neurons → kenyon cells
How is a dense combinatorial code turned into a sparse selective one?
kenyon cells receive input from multiple projection neurons and require multiple simultaneous inputs to fire, making firing selective
How are kenyon cells linked to dopaminergic neurons?
dopaminergic neurons response to reward/punishment
takes this info to kenyon cells so output is modified, leading to a behavior- leads to learning
GAL4/UAS system
binary expression system and allows us to artificially express arbitrary transgenes in specific cells
GAL4 binds to UAS and then recruits TFs to express whatever is upstream of UAS
GAL4
transcription factor found in yeast
under the control of an enhancer which will drive its expression in cells depending on where it is present
allowing cell specificity
UAS
upstream activating sequence
Split GAL4 system
GAL4 DNA binding domain and activation domain are split apart
put under the control of 2 different promoters which express different cells
only in the overlap where both are active they zipper together and can act as regular GAL4 again
Mushroom body
key structure in fly brain that regulates olfactory memory
made of kenyon cells with a peduncle connecting it to a vertical and horizontal lobe
How does the anatomy of the mushroom body relate to its function?
neurons called mushroom body output neurons
each different one innervates different ares of the L shaped lobe structure
this divides it up into different compartments
dopaminergic neurons folow same structure
What leads to the formation of approach/avoid behaviours?
express an optogenic factor in very specific neurons using the GAL4 system
can be trained when paired with odours
DANs are paired with MBONs of opposite valence
What does DAN/MBON pairing suggest about kenyon cells?
learning happens by weakening kenyon cell synpases onto output neurons
they synapse onto both approach and avoid neurons equally, leading to neutral behaviour
Pairing odour with shock
punish dopaminergic neurons modify synpase of odour activated kenyon cells and approach neurons
it is weakened so they ultimately avoid it as it is unbalanced
How do flies respond if the shock precedes odour?
learn backwards
they will learn to approach the odour as it predicts the relief from pain instead of pre-empting
What effect does shock then odour have on MBONs?
potentiation
What effect does odour then shock have on MBONs?
depression
D1 receptors
Gs signalling
acquisition/learning
odour-shock
D2 signalling
Gq signalling
forgetting
shock-odour
When does a drop in calcium in the ER occur?
when the reward/dopamine comes before odour
from Gq signalling
What defines which pathway will respond (forward learning or backward learning)?
whether it is IP3 or Ca2+ that reaches the IP3 receptor first
Ca2+ arrives first the channel will remain closed
IP3 arrives first the channel will open
IP3 binding receptor
there are 2 possible binding spots
Ca2+ can bind to one meaning the IP3 can cannot bind and open the channel
when IP3 binds first the Ca2+ can still bind and then channel will open
How is the mushroom body similar to a cerebellum like struture?
projection neurons crossing over kenyon cells is very similar to mossy fibres crossing granule cells
opposite nature of DANs and behavioural output similar to climbing fibres and purkijne cells
EPAC
sensor for cAMP- Gs signalling
ER-GcAMP
measures calcium in ER
Examples of habituation in humans
eye blink reflex
repetitive non harmful stimulus
visual attention
emotional repsonses
Early phase LTP
Ca2+ activation of CaMKII at NMDAr
Late phase
CREB2 is replaced by CREB1 which binds to CRE and then is phosphorylated
promotes transcription of LTP effectors
Habituation
reduced release of NTs due to RRP depletion
Associative learning
Ca2+ influx synergises 5-HT
Sensitisation
PKA phosphorylates K+ channels which increases duration of depolarisation
